|
1
|
Fonseca JM, Zloic SK, Ayogu CI, Marole KK, Ingold GC, Moreira SV, Soato Ratti MA. Deauville Score-Based Evaluation of Interim PET/CT in Follicular Lymphoma: A Prognostic Factor Systematic Review and Meta-Analysis. Cureus 2024; 16:e75169. [PMID: 39759650 PMCID: PMC11699972 DOI: 10.7759/cureus.75169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2024] [Indexed: 01/07/2025] Open
Abstract
Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma subtype, posing challenges in prognostication. While interim PET/CT is a recognized response assessment tool in other lymphoma subtypes, its prognostic value for FL remains uncertain. This study aims to evaluate the significance of interim PET results, which were assessed using the Deauville Score. A systematic review and meta-analysis were conducted across several databases, including studies that evaluated interim PET during frontline chemoimmunotherapy, with outcomes adjusted for other prognostic factors. Data extraction and risk of bias were performed independently by two authors. Hazard ratios (HR) and 95% confidence intervals (CI) were pooled using random-effects models, with leave-one-out sensitivity analyses to further assess the results. Four studies involving 427 patients were included. The pooled HR for Progression-Free Survival (PFS) was 2.88 (95% CI: 1.83-4.52; I² = 55.5%; p <0.0001), indicating a significant association between positive PET results and poorer PFS. The pooled HR for overall survival (OS) was 3.32 (95% CI: 1.34-8.23; I² = 74.4%; p = 0.0097), reflecting a significant decrease in OS with positive PET results. Sensitivity analyses confirmed the significance of these findings. Thus, positive interim PET results are associated with worse outcomes in frontline-treated FL patients, suggesting their potential as a valuable prognostic tool.
Collapse
Affiliation(s)
| | | | - Chukwudi I Ayogu
- Obstetrics and Gynaecology, Royal Liverpool University Hospital, Liverpool, GBR
| | - Karabo K Marole
- Medicine and Surgery, St. George's University School of Medicine, St. George, GRD
| | | | - Sarah V Moreira
- Radiology, Hospital Universitário da Universidade Federal de Juiz de Fora, Juiz de Fora, BRA
| | | |
Collapse
|
|
2
|
Li ZH, Zhang MY, Federico M, Civallero M, Manni M, Alonso-Alvarez S, Hou J, Huang HH. Early histological transformation of follicular lymphoma to diffuse large B-cell lymphoma indicating adverse survival: A population-based analysis and validation. Cancer 2024; 130:3321-3332. [PMID: 38809573 DOI: 10.1002/cncr.35378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 04/08/2024] [Accepted: 04/23/2024] [Indexed: 05/30/2024]
Abstract
INTRODUCTION The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. METHODS A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. RESULTS Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. CONCLUSION TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.
Collapse
MESH Headings
- Humans
- Lymphoma, Follicular/mortality
- Lymphoma, Follicular/pathology
- Lymphoma, Follicular/epidemiology
- Lymphoma, Large B-Cell, Diffuse/pathology
- Lymphoma, Large B-Cell, Diffuse/mortality
- Lymphoma, Large B-Cell, Diffuse/epidemiology
- Male
- Female
- Middle Aged
- Aged
- Retrospective Studies
- Prognosis
- SEER Program
- Cell Transformation, Neoplastic/pathology
- Adult
- Aged, 80 and over
Collapse
Affiliation(s)
- Zi-Hua Li
- Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min-Yue Zhang
- Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Massimo Federico
- Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Monica Civallero
- Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Martina Manni
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Sara Alonso-Alvarez
- Hospital Universitario Central de Asturias - Insituto de investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
| | - Jian Hou
- Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong-Hui Huang
- Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
3
|
Florindez JA, Chihara D, Reis IM, Lossos IS, Alderuccio JP. Risk of transformation by frontline management in follicular and marginal zone lymphomas: a US population-based analysis. Blood Adv 2024; 8:4423-4432. [PMID: 38954843 PMCID: PMC11375286 DOI: 10.1182/bloodadvances.2024013499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/10/2024] [Accepted: 06/23/2024] [Indexed: 07/04/2024] Open
Abstract
ABSTRACT Follicular lymphoma (FL) and marginal zone lymphoma (MZL) often have long overall survival (OS), however, high-grade transformation (HGT) to diffuse large B-cell lymphoma markedly reduces survival. The roles of upfront treatment vs observation on the incidence and outcome of HGT remain unclear. Thus, we analyzed a Surveillance, Epidemiology, and End Results database to address this question. Patients diagnosed with FL grades 1 to 2 or MZL between 2000 and 2020 were included. Fine-Gray models estimated the impact of covariates on HGT cumulative incidence and lymphoma-specific survival (LSS) and Cox regression on OS. HGT occurred in 4.2% of 23 384 patients with FL and 2.5% of 20 530 patients with MZL. The 5- and 10-year HGT cumulative incidence rates were 2.80% and 4.87% for FL, and 1.74% and 2.95% for MZL, respectively, which are notably lower than in earlier studies. The annual HGT incidence rate peaked in the first 2 years, then steadily declined over 2 decades for FL and all MZL subtypes. In FL, upfront observation vs treatment increases HGT risk (sub-distribution hazard ratio [SHR], 1.23; 95% confidence interval [CI], 1.09-1.40; P < .001) and barely affects OS (hazard ratio [HR], 0.95; 95% CI, 0.90-0.99; P = .03). Conversely, upfront observation was associated with lower HGT risk in nodal (SHR, 0.71; 95% CI, 0.53-0.94; P = .01) and extranodal (SHR, 0.64; 95% CI, 0.48-0.86; P = .003) MZL and did not affect survival in extranodal disease (HR, 0.94; 95% CI, 0.97-1.02; P = .15). HGT was associated with decrease in LSS across all histologies. Upfront treatment reduced the risk of HGT only in FL but not MZL.
Collapse
MESH Headings
- Humans
- Lymphoma, Follicular/therapy
- Lymphoma, Follicular/mortality
- Lymphoma, Follicular/epidemiology
- Lymphoma, B-Cell, Marginal Zone/therapy
- Lymphoma, B-Cell, Marginal Zone/epidemiology
- Lymphoma, B-Cell, Marginal Zone/mortality
- Male
- Female
- Middle Aged
- United States/epidemiology
- Aged
- SEER Program
- Incidence
- Adult
- Cell Transformation, Neoplastic
- Aged, 80 and over
- Disease Management
- Risk Factors
Collapse
Affiliation(s)
- Jorge A. Florindez
- Division of Hematology, The University of North Carolina Chapel Hill, Chapel Hill, NC
| | - Dai Chihara
- Department of Lymphoma & Myeloma, MD Anderson Cancer Center, Houston, TX
| | - Isildinha M. Reis
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL
- Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, Miami, FL
| | - Izidore S. Lossos
- Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
| | - Juan Pablo Alderuccio
- Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
| |
Collapse
|
|
4
|
Fernández-Miranda I, Pedrosa L, González-Rincón J, Espinet B, de la Cruz Vicente F, Climent F, Gómez S, Royuela A, Camacho FI, Martín-Acosta P, Yanguas-Casás N, Domínguez M, Méndez M, Colomo L, Salar A, Horcajo B, Navarro M, García-Cosío M, Piris-Villaespesa M, Llanos M, García JF, Sequero S, Mercadal S, García-Hernández S, Navarro B, Mollejo M, Provencio M, Sánchez-Beato M. Generation and External Validation of a Histologic Transformation Risk Model for Patients with Follicular Lymphoma. Mod Pathol 2024; 37:100516. [PMID: 38763418 DOI: 10.1016/j.modpat.2024.100516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 04/23/2024] [Accepted: 05/04/2024] [Indexed: 05/21/2024]
Abstract
Follicular lymphoma (FL) is the most frequent indolent lymphoma. Some patients (10%-15%) experience histologic transformation (HT) to a more aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). This study aimed to validate and improve a genetic risk model to predict HT at diagnosis.We collected mutational data from diagnosis biopsies of 64 FL patients. We combined them with the data from a previously published cohort (total n = 104; 62 from nontransformed and 42 from patients who did transform to DLBCL). This combined cohort was used to develop a nomogram to estimate the risk of HT. Prognostic mutated genes and clinical variables were assessed using Cox regression analysis to generate a risk model. The model was internally validated by bootstrapping and externally validated in an independent cohort. Its performance was evaluated using a concordance index and a calibration curve. The clinicogenetic nomogram included the mutational status of 3 genes (HIST1HE1, KMT2D, and TNFSR14) and high-risk Follicular Lymphoma International Prognostic Index and predicted HT with a concordance index of 0.746. Patients were classified as being at low or high risk of transformation. The probability HT function at 24 months was 0.90 in the low-risk group vs 0.51 in the high-risk group and, at 60 months, 0.71 vs 0.15, respectively. In the external validation cohort, the probability HT function in the low-risk group was 0.86 vs 0.54 in the high-risk group at 24 months, and 0.71 vs 0.32 at 60 months. The concordance index in the external cohort was 0.552. In conclusion, we propose a clinicogenetic risk model to predict FL HT to DLBLC, combining genetic alterations in HIST1H1E, KMT2D, and TNFRSF14 genes and clinical features (Follicular Lymphoma International Prognostic Index) at diagnosis. This model could improve the management of FL patients and allow treatment strategies that would prevent or delay transformation.
Collapse
MESH Headings
- Humans
- Lymphoma, Follicular/genetics
- Lymphoma, Follicular/pathology
- Female
- Male
- Middle Aged
- Aged
- Nomograms
- Adult
- Lymphoma, Large B-Cell, Diffuse/genetics
- Lymphoma, Large B-Cell, Diffuse/pathology
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/pathology
- Risk Assessment
- Aged, 80 and over
- Mutation
- Risk Factors
- Prognosis
- Biomarkers, Tumor/genetics
Collapse
Affiliation(s)
- Ismael Fernández-Miranda
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Lucía Pedrosa
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Julia González-Rincón
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain; CoE Data Intelligence, Fujitsu Technology Solutions S.A., Pozuelo de Alarcón, Madrid, Spain
| | - Blanca Espinet
- Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Department of Pathology, Hospital del Mar, Barcelona, Spain
| | - Fátima de la Cruz Vicente
- Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain
| | - Fina Climent
- Department of Pathology, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain
| | - Sagrario Gómez
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Ana Royuela
- Biostatistics Unit, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA. CIBERESP, ISCIII. Madrid, Spain
| | | | - Paloma Martín-Acosta
- Department of Pathology, Cancer Molecular Pathology Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Natalia Yanguas-Casás
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain; Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain
| | - Marina Domínguez
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Miriam Méndez
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain; Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Luis Colomo
- Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
| | - Antonio Salar
- Department of Hematology, Hospital del Mar, Barcelona, Spain
| | - Beatriz Horcajo
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Marta Navarro
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain
| | - Mónica García-Cosío
- Department of Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | - Marta Llanos
- Department of Oncology, Hospital Universitario de Canarias, Tenerife, Spain
| | - Juan F García
- Department of Pathology, Hospital MD Anderson Cancer Center, Madrid, Spain
| | - Silvia Sequero
- Department of Oncology, Hospital Universitario San Cecilio, Granada, Spain
| | - Santiago Mercadal
- Department of Hematology, ICO-Hospital Duran I Reynals, Barcelona, Spain
| | | | - Belén Navarro
- Department of Hematology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - Manuela Mollejo
- Department of Pathology, Complejo Hospitalario de Toledo, Spain
| | - Mariano Provencio
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain; Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Facultad de Medicina, Universidad Autónoma de Madrid, IDIPHISA, Madrid, Spain
| | - Margarita Sánchez-Beato
- Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain.
| |
Collapse
|
|
5
|
Rajamaki A, Sorigue M, Prusila REI, Kuusisto MEL, Kuitunen H, Jantunen E, Mercadal S, Turpeenniemi-Hujanen T, Sancho JM, Sunela K, Kuittinen O. Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice. Acta Oncol 2024; 63:267-272. [PMID: 38709114 PMCID: PMC11332539 DOI: 10.2340/1651-226x.2024.24377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 03/12/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. PATIENTS AND METHODS We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1-2 FL between 1997 and 2016 in nine institutions were included. RESULTS The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7-9.3 years), 4.2 years (95% CI: 2.8-5.6 years) and 2.2 years (95% CI 1.7-2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. INTERPRETATION With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.
Collapse
Affiliation(s)
- Aino Rajamaki
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Marc Sorigue
- Medical Department, Trialing Health, Barcelona, Spain.
| | - Roosa E I Prusila
- Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland
| | - Milla E L Kuusisto
- Department of Internal Medicine, Länsi-Pohja Central Hospital, Kemi, Finland
| | - Hanne Kuitunen
- Department of Internal Medicine, Länsi-Pohja Central Hospital, Kemi, Finland
| | - Esa Jantunen
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | | | - Taina Turpeenniemi-Hujanen
- Medical Research Center, Oulu University Hospital and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
| | - Juan-Manuel Sancho
- Department of Hematology, ICO-Hospital Germans Trias i Pujol, IJC, UAB, Badalona, Barcelona, Spain
| | - Kaisa Sunela
- Finnish Medicines Agency FIMEA, Barcelona, Spain
| | - Outi Kuittinen
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Medical Research Center, Oulu University Hospital and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Department of Oncology, Kuopio University Hospital, Kuopio, Finland
| |
Collapse
|
|
6
|
Watanabe T, Matsuno Y, Wakabayashi M, Maruyama D, Yamamoto K, Kubota N, Shimada K, Asagoe K, Yamaguchi M, Ando K, Ogura M, Kuroda J, Suehiro Y, Tsukasaki K, Tobinai K, Nagai H. Analyzing the risk factors for disease progression within 2 years and histological transformation in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone as first-line treatment: A 15-year follow-up of patients with advanced follicular lymphoma in JCOG0203. Hematol Oncol 2024; 42:e3272. [PMID: 38595316 DOI: 10.1002/hon.3272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/23/2024] [Accepted: 04/01/2024] [Indexed: 04/11/2024]
Abstract
Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment, we performed this post-hoc analysis of patients with advanced indolent B-cell lymphoma in a randomized clinical trial wherein six cycles of R-CHOP were administered every 2-3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676-9.466) and high- (OR 2.236, 95% CI 0.160-31.226) risks, B symptoms (OR 2.091, 95% CI 0.747-5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634-5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow-up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806-8.575) and high-risk FLIPI (OR 4.401, 95% CI 0.186-104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer-term analysis had a greater impact on HT. G3A and high-risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced-stage FL in future trials, particularly to address the unmet needs of patients with POD24.
Collapse
Affiliation(s)
- Takashi Watanabe
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
- Department of Personalized Control Science of Myeloid and Lymphoid Tumors, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yoshihiro Matsuno
- Department of Pathology, National Cancer Center Hospital, Tokyo, Japan
- Pathology Center, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
| | | | - Dai Maruyama
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
- Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kazuhito Yamamoto
- Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan
| | - Nobuko Kubota
- Department of Hematology, Saitama Cancer Center, Saitama, Japan
- Department of Hematology, Shin-Yurigaoka General Hospital, Kawasaki, Japan
| | - Kazuyuki Shimada
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kohsuke Asagoe
- Department of Hematology and Oncology, Shiga General Hospital, Moriyama, Japan
| | - Motoko Yamaguchi
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
- Department of Hematological Malignancies, Mie University Graduate School of Medicine, Tsu, Japan
| | - Kiyoshi Ando
- Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Michinori Ogura
- Department of Hematology and Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Junya Kuroda
- Division of Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Youko Suehiro
- Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Kunihiro Tsukasaki
- Department of Hematology, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Kensei Tobinai
- Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
| | - Hirokazu Nagai
- Department of Hematology and Oncology Research, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
| |
Collapse
|
|
7
|
Draye-Carbonnier S, Camus V, Becker S, Tonnelet D, Lévêque E, Zduniak A, Jardin F, Tilly H, Vera P, Decazes P. Prognostic value of the combination of volume, massiveness and fragmentation parameters measured on baseline FDG pet in high-burden follicular lymphoma. Sci Rep 2024; 14:8033. [PMID: 38580734 PMCID: PMC10997640 DOI: 10.1038/s41598-024-58412-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 03/28/2024] [Indexed: 04/07/2024] Open
Abstract
The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan-Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p < 0.001), high Tumor Volume Surface Ratio (TVSR) (HR = 3.204; p < 0.003) and high medPCD (HR = 4.507; p < 0.001) had significantly worse prognosis in both Kaplan-Meier and Cox univariate analyses. Furthermore, a synergistic effect was observed in Kaplan-Meier and Cox analyses combining these three PET/CT-derived parameters (HR = 12.562; p < 0.001). Having two or three high parameters among TMTV, TVSR and medPCD was able to predict POD24 status with a specificity of 68% and a sensitivity of 75%. TMTV, TVSR and baseline medPCD are strong prognostic factors in FL and their combination better predicts disease prognosis.
Collapse
Affiliation(s)
| | - V Camus
- Department of Hematology, Centre Henri Becquerel, Rouen, France
- INSERM U1245, Université de Rouen, IRIB, Rouen, France
| | - S Becker
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France
- QuantIF-LITIS (EA 4108-FR CNRS 3638), Faculty of Medicine, University of Rouen, Rouen, France
| | - D Tonnelet
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France
| | - E Lévêque
- Department of Statistics and Clinical Research Unit, Centre Henri Becquerel, Rouen, France
| | - A Zduniak
- Department of Hematology, Centre Henri Becquerel, Rouen, France
| | - F Jardin
- Department of Hematology, Centre Henri Becquerel, Rouen, France
- INSERM U1245, Université de Rouen, IRIB, Rouen, France
| | - H Tilly
- Department of Hematology, Centre Henri Becquerel, Rouen, France
- INSERM U1245, Université de Rouen, IRIB, Rouen, France
| | - P Vera
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France
- QuantIF-LITIS (EA 4108-FR CNRS 3638), Faculty of Medicine, University of Rouen, Rouen, France
| | - P Decazes
- Department of Nuclear Medicine, Centre Henri Becquerel, Rouen, France.
- QuantIF-LITIS (EA 4108-FR CNRS 3638), Faculty of Medicine, University of Rouen, Rouen, France.
| |
Collapse
|
|
8
|
Zheng W, Liu M, Guan L, Wang S. Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study. Cancer Med 2024; 13:e7120. [PMID: 38629251 PMCID: PMC11022146 DOI: 10.1002/cam4.7120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 02/24/2024] [Accepted: 03/09/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. METHODS We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. RESULTS Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. CONCLUSION The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.
Collapse
Affiliation(s)
- Wenshuai Zheng
- Department of HematologyHainan Hospital of Chinese PLA General HospitalSanyaChina
| | - Mingjuan Liu
- Senior Department of HematologyFifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Lixun Guan
- Department of HematologyHainan Hospital of Chinese PLA General HospitalSanyaChina
| | - Shenyu Wang
- Senior Department of HematologyFifth Medical Center of Chinese PLA General HospitalBeijingChina
| |
Collapse
|
|
9
|
Obeid J, Hiniker SM, Schroers‐Martin J, Guo HH, No HJ, Moding EJ, Advani RH, Alizadeh AA, Hoppe RT, Binkley MS. Investigating and modeling positron emission tomography factors associated with large cell transformation from low-grade lymphomas. EJHAEM 2023; 4:90-99. [PMID: 36819184 PMCID: PMC9928791 DOI: 10.1002/jha2.615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/27/2022] [Accepted: 10/31/2022] [Indexed: 11/27/2022]
Abstract
Low-grade lymphomas have a 1%-3% annual risk of transformation to a high-grade histology, and prognostic factors remain undefined. We set to investigate the role of positron emission tomography (PET) metrics in identification of transformation in a retrospective case-control series of patients matched by histology and follow-up time. We measured PET parameters including maximum standard uptake value (SUV-max) and total lesion glycolysis (TLG), and developed a PET feature and lactate dehydrogenase (LDH)-based model to identify transformation status within discovery and validation cohorts. For our discovery cohort, we identified 53 patients with transformation and 53 controls with a similar distribution of follicular lymphoma (FL). Time to transformation and control follow-up time was similar. We observed a significant incremental increase in SUV-max and TLG between control, pretransformation and post-transformation groups (P < 0.05). By multivariable analysis, we identified a significant interaction between SUV-max and TLG such that SUV-max had highest significance for low volume cases (P = 0.04). We developed a scoring model incorporating SUV-max, TLG, and serum LDH with improved identification of transformation (area under the curve [AUC] = 0.91). Our model performed similarly for our validation cohort of 23 patients (AUC = 0.90). With external and prospective validation, our scoring model may provide a specific and noninvasive tool for risk stratification for patients with low-grade lymphoma.
Collapse
Affiliation(s)
- Jean‐Pierre Obeid
- Department of Radiation OncologyStanford University School of MedicineStanfordCaliforniaUSA
| | - Susan M. Hiniker
- Department of Radiation OncologyStanford University School of MedicineStanfordCaliforniaUSA
| | - Joseph Schroers‐Martin
- Department of MedicineDivision of Oncology, Stanford University School of MedicineStanfordCaliforniaUSA
| | - H. Henry Guo
- Department of RadiologyStanford University School of MedicineStanfordCaliforniaUSA
| | - Hyunsoo Joshua No
- Department of Radiation OncologyStanford University School of MedicineStanfordCaliforniaUSA
| | - Everett J. Moding
- Department of Radiation OncologyStanford University School of MedicineStanfordCaliforniaUSA
| | - Ranjana H. Advani
- Department of MedicineDivision of Oncology, Stanford University School of MedicineStanfordCaliforniaUSA
| | - Ash A. Alizadeh
- Department of MedicineDivision of Oncology, Stanford University School of MedicineStanfordCaliforniaUSA
| | - Richard T. Hoppe
- Department of Radiation OncologyStanford University School of MedicineStanfordCaliforniaUSA
| | - Michael S. Binkley
- Department of Radiation OncologyStanford University School of MedicineStanfordCaliforniaUSA
| |
Collapse
|
|
10
|
Casulo C, Herold M, Hiddemann W, Iyengar S, Marcus RE, Seymour JF, Launonen A, Knapp A, Nielsen TG, Mir F. Risk Factors for and Outcomes of Follicular Lymphoma Histological Transformation at First Progression in the GALLIUM Study. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:40-48. [PMID: 36379880 DOI: 10.1016/j.clml.2022.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Although advanced‑stage follicular lymphoma (FL) is considered incurable, survival has improved with the introduction of the anti-CD20 antibodies, rituximab (R) and obinutuzumab (G). However, FL can undergo histological transformation (HT) to a more aggressive disease, and a validated model for predicting HT risk is not yet available. PATIENTS AND METHODS We assessed HT incidence, risk factors and outcomes in the phase III, GALLIUM study evaluating R- or G-chemotherapy in patients with previously untreated, advanced-stage FL (ClinicalTrials.gov NCT01332968). HT rates were assessed by repeat tumour biopsy at disease progression or relapse, at the investigator's discretion. RESULTS Of 1202 patients enrolled, 315 (26.2%) experienced progressive disease; 46 (14.6%) had a biopsy at first progression, 40 of whom had biopsy-confirmed HT. HT risk factors were male sex (subdistribution hazard ratio [sHR], 2.21; 95% confidence interval [CI], 1.16-4.20), elevated baseline serum lactate dehydrogenase (sHR, 3.97; 95% CI, 2.03-7.76), and elevated baseline serum β2-microglobulin (sHR, 1.96; 95% CI, 1.02-3.79). Patients with HT at first progression had poorer post-progression survival than those with relapsed FL (2-year rate: 55.9% vs. 83.1%). Relapse with HT occurred earlier than FL relapse (median time from randomisation: 0.8 vs. 2.3 years). CONCLUSION HT was a low-frequency event associated with poor survival outcomes in the GALLIUM study. Male sex and elevated baseline levels of serum LDH and B2M were significant risk factors for HT. Further research is required to develop validated prognostic indices for HT risk and guide treatment decisions.
Collapse
Affiliation(s)
- Carla Casulo
- University of Rochester Medical Center, Rochester, NY.
| | - Michael Herold
- Department of Medicine, HELIOS-Klinikum Erfurt, Erfurt, Germany
| | - Wolfgang Hiddemann
- Department of Hematology and Oncology, Ludwig Maximilian University of Munich, Munich, Germany
| | - Sunil Iyengar
- Department of Haemato-oncology, Royal Marsden Hospital, London, UK
| | | | - John F Seymour
- Department of Haematology, Peter MacCallum Cancer Centre, Royal Melbourne Hospital & University of Melbourne, Victoria, Australia
| | | | | | | | - Farheen Mir
- Department of Haemato-oncology, Royal Marsden Hospital, London, UK
| |
Collapse
|
|
11
|
Perrett M, Edmondson C, Okosun J. Biology of follicular lymphoma: insights and windows of clinical opportunity. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2022; 2022:688-694. [PMID: 36485095 PMCID: PMC9820323 DOI: 10.1182/hematology.2022000361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Follicular lymphoma (FL) is a heterogeneous disease, both clinically and biologically. The biological behavior and development of FL is a culmination of complex multistep processes underpinned by genetic and nongenetic determinants. Epigenetic deregulation through recurrent genetic alterations is now a recognized major biological hallmark of FL, alongside the t(14;18) translocation. In parallel, there is a strong interplay between the lymphoma B cells and the immune microenvironment, with the microenvironment serving as a critical enabler by creating a tumor-supportive niche and modulating the immune response to favor survival of the malignant B cells. A further layer of complexity arises from the biological heterogeneity that occurs between patients and within an individual, both over the course of the disease and at different sites of disease involvement. Altogether, taking the first steps to bridge the understanding of these various biological components and how to evaluate these clinically may aid and inform future strategies, including logical therapeutic interventions, risk stratification, therapy selection, and disease monitoring.
Collapse
Affiliation(s)
- Megan Perrett
- Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Carina Edmondson
- Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Jessica Okosun
- Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK
| |
Collapse
|
|
12
|
Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk. Nat Commun 2022; 13:6772. [PMID: 36351924 PMCID: PMC9646774 DOI: 10.1038/s41467-022-34408-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 10/20/2022] [Indexed: 11/11/2022] Open
Abstract
Follicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling of both tumor and immune compartments in 155 diagnostic FL biopsies at single-cell resolution by mass cytometry. This revealed a diversity of phenotypes but included two recurrent patterns, one which closely resembles germinal center B-cells (GCB) and another which appears more related to memory B-cells (MB). GCB-type tumors are enriched for EZH2, TNFRSF14, and MEF2B mutations, while MB-type tumors contain increased follicular helper T-cells. MB-type and intratumoral phenotypic diversity are independently associated with increased risk of transformation, supporting biological relevance of these features. Notably, a reduced 26-marker panel retains sufficient information to allow phenotypic profiling of future cohorts by conventional flow cytometry.
Collapse
|
|
13
|
Genetics of Transformed Follicular Lymphoma. HEMATO 2022. [DOI: 10.3390/hemato3040042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Histological transformation (HT) to a more aggressive disease–mostly diffuse large B-cell lymphoma–is considered one of the most dismal events in the clinical course of follicular lymphoma (FL). Current knowledge has not found a single biological event specific for HT, although different studies have highlighted common genetic alterations, such as TP53 and CDKN2A/B loss, and MYC translocations, among others. Together, they increase genomic complexity and mutational burden at HT. A better knowledge of HT pathogenesis would presumably help to find diagnostic biomarkers allowing the identification of patients at high-risk of transformation, as well as the discrimination from patients with FL recurrence, and those who remain in remission. This would also help to identify new drug targets and the design of clinical trials for the treatment of transformation. In the present review we provide a comprehensive overview of the genetic events frequently identified in transformed FL contributing to the switch towards aggressive behaviour, and we will discuss current open questions in the field of HT.
Collapse
|
|
14
|
Survival Outcomes of Patients with Follicular Lymphoma after Relapse or Progression: A Single-Center Real-World Data Analysis. JOURNAL OF ONCOLOGY 2022; 2022:2263217. [PMID: 36199784 PMCID: PMC9529394 DOI: 10.1155/2022/2263217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 09/06/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022]
Abstract
Background Follicular lymphoma (FL) is considered incurable because remission and relapse are common. Although various salvage treatment options have been proposed, there is no consensus on treatment strategy for FL patients who failed primary treatment. Methods This single-center study analyzed postevent overall survival (OS) among 70 patients who experienced relapse or progression after rituximab-containing immunochemotherapy according to type of salvage treatment and nature of relapse or progression. Results Of 70 patients, 42 experienced progression of disease within 24 months (POD24), and six showed disease progression during first-line treatment. Large-cell transformation was found in nine patients with POD24. At the median follow-up of 104 months (95% CI: 90-118 months), POD24 patients experienced significantly worse OS than patients without POD24, and postevent OS was not satisfactory after conventional salvage chemotherapy because the majority of patients relapsed or progressed. However, autologous stem cell transplantation (ASCT) after the first relapse resulted in survival prolongation in patients with POD24. Half of the patients (34/67, 51%) participated in at least one clinical trial during treatment after first relapse, and patients participating in at least one clinical trial irrespective of line of treatment tended to experience better survival. Conclusions Relapsed or refractory FL patients showed various clinical courses and treatment outcomes according to relapse or progression. Consolidation treatment with ASCT and active participation to clinical trials might prolong survival duration, especially in POD24 cases.
Collapse
|
|
15
|
Mozas P, Rivero A, Rivas-Delgado A, Correa JG, Condom M, Nadeu F, Giné E, Delgado J, Villamor N, Campo E, Magnano L, López-Guillermo A. Prognostic ability of five clinical risk scores in follicular lymphoma: A single-center evaluation. Hematol Oncol 2021; 39:639-649. [PMID: 34494300 DOI: 10.1002/hon.2922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 11/06/2022]
Abstract
With the intention of identifying follicular lymphoma (FL) patients at higher risk of progression, early relapse (POD24), histological transformation (HT) or death, multiple risk scores (RS) have been proposed. However, it has not yet been established whether any of them globally outperforms the others. We evaluated the clinical utility and statistical performance of the five most widely used clinical scores (IPI, ILI, FLIPI, FLIPI2, PRIMA-PI) in a single-center series of 414 grade 1-3A FL patients diagnosed in the rituximab era. Overall concordance (proportion of patients allocated to the same risk category by all five RS) was 24%. FLIPI and FLIPI2 were predictive of time to first treatment. All five scores were predictive of response, POD24, progression-free, and OS, while only FLIPI predicted HT. IPI identified a small subset (7%) of truly high-risk patients (10-year OS of 16%). In subgroup analyses, we showed that ILI is useful in the prognostication of limited-disease patients, and PRIMA-PI is an age-independent score that can identify a high-risk subset of older patients. Performance metrics were slightly better for IPI in terms of calibration (Harrell's c-index 0.73), without major differences among RS regarding other parameters. Although the incorporation of molecular and imaging data will continue to refine the stratification of FL patients, FLIPI remains the most powerful clinical prognostic index in the rituximab era, predicting the greatest number of endpoints.
Collapse
Affiliation(s)
- Pablo Mozas
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Andrea Rivero
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
| | | | | | - Maria Condom
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Ferran Nadeu
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Eva Giné
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Julio Delgado
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Neus Villamor
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Hematopathology Unit, Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Elías Campo
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Hematopathology Unit, Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain.,Universitat de Barcelona, Spain
| | - Laura Magnano
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Armando López-Guillermo
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Universitat de Barcelona, Spain
| |
Collapse
|
|
16
|
Mozas P, Rivero A, López-Guillermo A. Past, present and future of prognostic scores in follicular lymphoma. Blood Rev 2021; 50:100865. [PMID: 34187710 DOI: 10.1016/j.blre.2021.100865] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/17/2021] [Accepted: 06/21/2021] [Indexed: 12/11/2022]
Abstract
Although most follicular lymphoma (FL) patients have prolonged survival, the identification of those at risk of early progression, multiple relapses or histological transformation is essential for the improvement of long-term outcomes. In this sense, a plethora of prognostic indexes have been developed in the last decades. However, determining which one is more accurate and clinically meaningful remains a challenge. Key factors for the external validity of available indexes include characteristics of the study population, treatment intervention, and design of the study. While initial risk scores were composed of clinical, biochemical, and hematological variables, genomic and imaging data have been incorporated in recent years. Despite an obvious step forward in the knowledge of the natural history and biology of FL, predictions remain inaccurate. Further research will likely incorporate information from circulating tumor DNA and artificial intelligence models to refine the prognostic classification of the heterogeneous FL population.
Collapse
Affiliation(s)
- Pablo Mozas
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain.
| | - Andrea Rivero
- Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain
| | | |
Collapse
|
|
17
|
Alzahrani M. Age-adjusted survival analysis of lymphoma patients diagnosed from extranodal sites. JOURNAL OF NATURE AND SCIENCE OF MEDICINE 2021. [DOI: 10.4103/jnsm.jnsm_29_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
18
|
Abstract
Histologic transformation of follicular lymphoma remains the leading cause of follicular lymphoma-related mortality in the rituximab era. Both the diverse timing of transformation and heterogeneity in associated genomic events suggest that histologic transformation may itself comprise distinct disease entities. Successive indolent and transformation episodes occur by divergent clonal evolution from an inferred common progenitor cell, representing a potential therapeutic target. Existing biological knowledge largely pre-dates anti-CD20 therapy, and further prospective validation is essential. Inclusion of transformation cases in clinical trials incorporating biomarker discovery, and an integrated understanding of the genetic and microenvironmental factors underpinning transformation, may unearth renewed clinical opportunities.
Collapse
Affiliation(s)
- Emil A Kumar
- Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
| | - Jessica Okosun
- Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK
| | - Jude Fitzgibbon
- Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. https://twitter.com/fitzgi02
| |
Collapse
|
|
19
|
Lim RMH, Chan NPX, Khoo LP, Cheng CL, Tan L, Poon EYL, Somasundaram N, Farid M, Tang TPL, Tao M, Lim ST, Chan JY. A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in Asian patients treated in the Rituximab Era. Sci Rep 2020; 10:4373. [PMID: 32152442 PMCID: PMC7062756 DOI: 10.1038/s41598-020-61378-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 01/24/2020] [Indexed: 11/09/2022] Open
Abstract
Composite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is uncommonly found on lymph node biopsy and represents a rare haematological malignancy. We aim to examine clinico-pathological features of patients with FL/DLBCL and investigate predictors of survival outcome. We included in our retrospective study patients with histologically-proven FL/DLBCL at diagnosis (n = 106) and who were subsequently treated with rituximab-based chemoimmunotherapy from 2002–2017 at the National Cancer Centre. The cohort consisted of 34 women and 72 men with a median age of 59 years (range, 24–82). In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, advanced stage (p = 0.0136), presence of MYC and/or BCL6 rearrangement (p = 0.0376) and presence of B symptoms (p = 0.0405) were independently prognostic for worse overall survival (OS). The only remaining independent prognostic variables for worse OS after including first-line treatment data in the model were use of chemotherapy regimens other than R-CHOP (p = 0.0360) and lack of complete response to chemotherapy (p < 0.0001) besides the presence of B symptoms (p = 0.0022). We generated a Clinico-Genotypic Index by point-wise addition of all five adverse parameters (score of 0–1, 2, 3, 4–5) which revealed four prognostic risk groups with a predicted 5-year OS of 100%, 62%, 40% and 0% (p < 0.0001) accounting for 50.0%, 24.5%, 18.9% and 6.6% of the cohort respectively. We propose that R-CHOP should be the recommended first-line regimen for composite FL/DLBCL.
Collapse
Affiliation(s)
- Ryan Mao Heng Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Natalie Pei Xin Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Lay Poh Khoo
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Chee Leong Cheng
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - Leonard Tan
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - Eileen Yi Ling Poon
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore
| | - Nagavalli Somasundaram
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore
| | - Mohamad Farid
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
| | - Tiffany Pooi Ling Tang
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
| | - Miriam Tao
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
| | - Soon Thye Lim
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore. .,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore. .,Duke-NUS Medical School, Singapore, Singapore.
| | - Jason Yongsheng Chan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore. .,SingHealth Duke-NUS Blood Cancer Centre, Singapore, Singapore. .,Duke-NUS Medical School, Singapore, Singapore. .,Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
| |
Collapse
|
|
20
|
Enhancement of the Follicular Lymphoma International Prognostic Index (FLIPI) with lymphopenia (FLIPI-L): a predictor for overall survival and histologic transformation. Blood Cancer J 2020; 9:104. [PMID: 31894139 PMCID: PMC6938796 DOI: 10.1038/s41408-019-0269-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 11/18/2019] [Accepted: 11/25/2019] [Indexed: 11/08/2022] Open
|
|
21
|
Ohmoto A, Fuji S. Histological transformation in malignant lymphoma: a possible role of PET/CT and circulating tumor DNA as noninvasive diagnostic tools. Expert Rev Hematol 2019; 13:23-30. [PMID: 31701788 DOI: 10.1080/17474086.2020.1690987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: Transformation is a multi-step event wherein indolent lymphomas, such as follicular lymphomas, are converted into an aggressive subtype, such as diffuse large B-cell lymphoma. This process progresses not only through mutations in several of the causative genes, such as TP53, CDKN2A/B, or MYC, but also through epigenetic or micro-environmental changes. Excisional biopsy is recommended when transformation is clinically suspected.Areas covered: The authors summarized the current knowledge regarding the clinicopathological and molecular features of transformed lymphomas and discussed the relevance of re-biopsy in the diagnosis of transformation, comparing it with noninvasive diagnostic tools [fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and circulating tumor DNA (ctDNA) analysis].Expert opinion: Pathological confirmation by biopsy is considered the golden standard for diagnosis and is indispensable for determining subsequent treatment strategies. The potential weakness of this approach is its invasiveness and the unavailability of pathological findings outside the biopsied areas. In the context of relapse, PET/CT is used mainly for the selection of the best suitable biopsy site, while ctDNA has the potential for detecting systemic genomic changes associated with relapse before clinical presentation. Future investigations should be focused on combining biopsies with new technologies for an early and accurate diagnosis of transformation.
Collapse
Affiliation(s)
- Akihiro Ohmoto
- Division of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shigeo Fuji
- Department of Hematology, Osaka International Cancer Institute, Osaka, Japan
| |
Collapse
|
|
22
|
Behdad A, Boddy CS, Fought AJ, Taxter T, Falkiewicz MK, Ayers E, Chen QC, Chen YH, Karmali R, Pro B, Winter JN, Landsburg DJ, Gordon LI, Kaplan JB. Survival outcomes of diffuse large B-cell lymphoma by association with concurrent or antecedent follicular lymphoma and double hit status. Leuk Lymphoma 2019; 60:3266-3271. [PMID: 31225766 DOI: 10.1080/10428194.2019.1622099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL) (tDLBCL) has been traditionally associated with an aggressive course, but more recent studies have shown longer survivals. The clinical significance of concurrent FL at the time of diagnosis of DLBCL (cDLBCL/FL) is less clear. We compared outcomes of tDLBCL, cDLBCL/FL, and de novo DLBCL (dDLBCL) and then evaluated the impact of double hit (DH) rearrangements (MYC with BCL2 and/or BCL6) in these subgroups' outcomes. The progression free survival (PFS) and overall survival (OS) were not significantly different among the three groups (dDLBCL, tDLBCL, and cDLBCL/FL). The effect of DH on survival was then analyzed in two subgroups: (1) dDLBCL and (2) tDLBCL + cDLBCL/FL. PFS and OS were significantly shorter in lymphomas with DH in each of these two subgroups. We conclude that DH status drives outcomes in all DLBCLs, regardless of their transformation status.
Collapse
Affiliation(s)
- Amir Behdad
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Craig S Boddy
- Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Angela J Fought
- Department of Preventive Medicine, Division of Biostatistics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Timothy Taxter
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Marissa K Falkiewicz
- Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
| | - Emily Ayers
- Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
| | - Qing C Chen
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Yi-Hua Chen
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Reem Karmali
- Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Barbara Pro
- Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Jane N Winter
- Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Daniel J Landsburg
- Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
| | - Leo I Gordon
- Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Jason B Kaplan
- Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| |
Collapse
|
|
23
|
Méndez M, Torrente M, Sánchez-Beato M, González-Rincón J, Royuela A, Gómez-Codina J, de la Cruz-Merino L, Rueda A, Llanos M, Quero C, Rodríguez-Abreu D, Gumá J, Monsalvo S, Sabin P, Provencio M. Transformed follicular lymphoma in the rituximab era: A report from the Spanish Lymphoma Oncology Group. Hematol Oncol 2019; 37:143-150. [PMID: 30840776 DOI: 10.1002/hon.2601] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 02/18/2019] [Accepted: 02/26/2019] [Indexed: 11/10/2022]
Abstract
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish registry. Sixty-four HTs were recorded based on clinical criteria (55%) or histological confirmation (45%). The cumulative incidence rate of transformation at 5 years is 7.3%. The 5-year overall survival (OS) without HT was 85% (95% confidence interval [CI], 70%-90%) vs 66% (95% CI, 51%-76%; P = 0.0012) with HT. Factors associated with HT were elevated lactate dehydrogenase (LDH) (odds ratio [OR] 1.83), intermediate-high Follicular lymphoma international prognostic index (FLIPI) (OR 2.16-OR 3.21), B symptoms (OR 2.46), or Eastern Cooperative Oncology Group (ECOG) 1 (OR 2.35). Treatment options related to HT were "watch and wait" or no rituximab or anthracyclines initially. A 5-year OS for patients treated with chemotherapy before HT was 55% (95% CI, 38%-69%) versus 81% (95% CI, 53%-93%; P = 0.009) for those who had not received it. The HT rate has decreased after the introduction of rituximab, as has been previously described. The timing of this treatment had an impact on the survival of these patients.
Collapse
Affiliation(s)
- Miriam Méndez
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Maria Torrente
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Margarita Sánchez-Beato
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Julia González-Rincón
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Ana Royuela
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| | - José Gómez-Codina
- Medical Oncology Department, Hospital Universitario La Fe de Valencia, Valencia, Spain
| | | | - Antonio Rueda
- Medical Oncology Department, Hospital Universitario Costa del Sol, Marbella, Spain
| | - Marta Llanos
- Medical Oncology Department, Hospital Universitario de Canarias, Canary Islands, Spain
| | - Cristina Quero
- Medical Oncology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Delvys Rodríguez-Abreu
- Medical Oncology Department, Complejo Hospitalario Universitario Insular de Canarias, Canary Islands, Spain
| | - Josep Gumá
- Medical Oncology Department, Hospital Universitari Sant Joan de Reus, Tarragona, Spain
| | - Silvia Monsalvo
- Medical Oncology Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Pilar Sabin
- Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Mariano Provencio
- Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
| |
Collapse
|
|
24
|
Alessandrino F, DiPiro PJ, Jagannathan JP, Babina G, Krajewski KM, Ramaiya NH, Giardino AA. Multimodality imaging of indolent B cell lymphoma from diagnosis to transformation: what every radiologist should know. Insights Imaging 2019; 10:25. [PMID: 30796644 PMCID: PMC6386758 DOI: 10.1186/s13244-019-0705-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 11/14/2018] [Indexed: 12/28/2022] Open
Abstract
Indolent B cell lymphomas are a group of lymphoid malignancies characterized by their potential to undergo histologic transformation to aggressive lymphomas. While different subtypes of indolent B cell lymphomas demonstrate specific clinical and imaging features, histologic transformation can be suspected on cross-sectional imaging when disproportionate lymph node enlargement or new focal lesions in extranodal organs are seen. On PET/CT, transformed indolent lymphoma may show new or increased nodal FDG avidity or new FDG-avid lesions in different organs. In this article, we will (1) review the imaging features of different subtypes of indolent B cell lymphomas, (2) discuss the imaging features of histologic transformation, and (3) propose a diagnostic algorithm for transformed indolent lymphoma. The purpose of this review is to familiarize radiologists with the spectrum of clinical and imaging features of indolent B cell lymphomas and to define the role of imaging in raising concern for transformation and in guiding biopsy for confirmation.
Collapse
Affiliation(s)
- Francesco Alessandrino
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
| | - Pamela J DiPiro
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Jyothi P Jagannathan
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Gosangi Babina
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Katherine M Krajewski
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Nikhil H Ramaiya
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
- Department of Radiology, UH Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | - Angela A Giardino
- Department of Imaging, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| |
Collapse
|
|
25
|
Sutamtewagul G, Link BK. Novel treatment approaches and future perspectives in follicular lymphoma. Ther Adv Hematol 2019; 10:2040620718820510. [PMID: 30719267 PMCID: PMC6348550 DOI: 10.1177/2040620718820510] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 11/30/2018] [Indexed: 12/14/2022] Open
Abstract
Follicular lymphoma (FL) is a common B-cell malignancy characterized by relatively indolent growth and incurability with an expected lifetime course of serial intermittent treatment courses. Many patients with FL have lives shortened by the disease and despite a relatively favorable prognosis relative to other incurable systemic malignancies, optimal management of FL has not been achieved. This review focuses on identifying both patients for whom novel therapies might be most beneficial as well as systematically reviewing novel strategies at various levels of investigation. Prognostic markers incorporating clinical measurements and tumor genetics are discussed, yet at the time of diagnosis do not yet powerfully discriminate patients for whom specific strategies are beneficial. Reassessment of prognosis after evaluating the response to initial therapy is the most powerful identifier of those in need of novel management strategies. For initial therapy of high burden systemic disease, anti-CD20 antibody along with chemotherapy or immunomodulators all offer relatively similar effects on overall survival with subtly different effects on progression-free survival and quality of life. Several new agents currently under investigation in the upfront setting are discussed. Perhaps the best testing ground for novel therapies is in patients with early relapse following initial immunochemotherapy. Ongoing research in multiple therapy classes including, novel monoclonal antibodies, antibody drug conjugates, immunomodulatory agents, intracellular pathway inhibitors, immune checkpoint inhibitors, and epigenetic regulators are discussed herein.
Collapse
Affiliation(s)
- Grerk Sutamtewagul
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Dr., C305 GH, Iowa City, IA 52242, USA
| | - Brian K. Link
- Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| |
Collapse
|
|
26
|
Nastoupil LJ, Flowers CR, Leonard JP. Sequencing of therapies in relapsed follicular lymphoma. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2018; 2018:189-193. [PMID: 30504309 PMCID: PMC6245973 DOI: 10.1182/asheducation-2018.1.189] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Follicular lymphoma (FL) is an incurable but treatable disease with vast treatment options. Despite the abundance of efficacious treatment modalities, there is no universally agreed upon standard approach to treatment, particularly in the relapsed/refractory setting. There is an increasing need for more robust and clinically available tools to risk-stratify patients and identify those likely to experience early relapse, which is currently recognized as the unmet need in FL. Additionally, the use of gene-expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis. However, much of this knowledge is not currently available in the clinic to inform treatment decisions. Future studies are needed to generate clinically relevant predictive models adept at incorporating patient-specific and molecular features to inform management strategies along the entire disease continuum as treatment decisions should not be made in a vacuum with a one-size-fits-all approach. Sequencing of therapy in the management of relapsed FL should involve personalized decision-making for care plans that balance patient characteristics, preferences, and comorbidities with treatment-related factors such as efficacy, toxicity profile, and mechanisms of action to achieve a durable, quality remission.
Collapse
Affiliation(s)
- Loretta J. Nastoupil
- Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Christopher R. Flowers
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA; and
| | - John P. Leonard
- Division of Hematology and Medical Oncology, Meyer Cancer Center, Weill Cornell Medicine and NewYork-Presbyterian Hospital, New York, NY
| |
Collapse
|
|
27
|
Roisman A, Castellano G, Navarro A, Gonzalez-Farre B, Pérez-Galan P, Esteve-Codina A, Dabad M, Heath S, Gut M, Bosio M, Bellot P, Salembier P, Oliveras A, Slavutsky I, Magnano L, Horn H, Rosenwald A, Ott G, Aymerich M, López-Guillermo A, Jares P, Martín-Subero JI, Campo E, Hernández L. Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas. Br J Haematol 2018; 184:373-383. [DOI: 10.1111/bjh.15656] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 09/11/2018] [Indexed: 01/03/2023]
Affiliation(s)
- Alejandro Roisman
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Laboratorio de Genética de Neoplasias Linfoides; Instituto de Medicina Experimental; CONICET-Academia Nacional de Medicina; Buenos Aires Argentina
| | | | - Alba Navarro
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Barcelona Spain
| | - Blanca Gonzalez-Farre
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Department of Pathology; Hospital Clínic; University of Barcelona; Barcelona Spain
| | - Patricia Pérez-Galan
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
| | - Anna Esteve-Codina
- CNAG-CRG; Centre for Genomic Regulation (CRG); Barcelona Institute of Science and Technology (BIST); Barcelona Spain
- Universitat Pompeu Fabra (UPF); Barcelona Spain
| | - Marc Dabad
- CNAG-CRG; Centre for Genomic Regulation (CRG); Barcelona Institute of Science and Technology (BIST); Barcelona Spain
- Universitat Pompeu Fabra (UPF); Barcelona Spain
| | - Simon Heath
- CNAG-CRG; Centre for Genomic Regulation (CRG); Barcelona Institute of Science and Technology (BIST); Barcelona Spain
- Universitat Pompeu Fabra (UPF); Barcelona Spain
| | - Marta Gut
- CNAG-CRG; Centre for Genomic Regulation (CRG); Barcelona Institute of Science and Technology (BIST); Barcelona Spain
- Universitat Pompeu Fabra (UPF); Barcelona Spain
| | - Mattia Bosio
- Barcelona Supercomputing Center; Barcelona Spain
| | - Pau Bellot
- Department of Signal Theory and Communications; Technical University of Catalonia UPC; Barcelona Spain
| | - Philippe Salembier
- Department of Signal Theory and Communications; Technical University of Catalonia UPC; Barcelona Spain
| | - Albert Oliveras
- Department of Signal Theory and Communications; Technical University of Catalonia UPC; Barcelona Spain
| | - Irma Slavutsky
- Laboratorio de Genética de Neoplasias Linfoides; Instituto de Medicina Experimental; CONICET-Academia Nacional de Medicina; Buenos Aires Argentina
| | - Laura Magnano
- Department of Haematology; Hospital Clínic of Barcelona; Barcelona Spain
| | - Heike Horn
- Dr. M. Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart and University of Tübingen; Stuttgart Germany
| | | | - German Ott
- Department of Clinical Pathology; Robert-Bosch Krankenhaus; Stuttgart Germany
| | - Marta Aymerich
- Haematopathology Unit; Department of Pathology; Hospital Clínic; IDIBAPS; Barcelona Spain
| | | | - Pedro Jares
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Department of Pathology; Hospital Clínic; University of Barcelona; Barcelona Spain
| | - José I. Martín-Subero
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Barcelona Spain
| | - Elías Campo
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Barcelona Spain
- Haematopathology Unit; Department of Pathology; Hospital Clínic; IDIBAPS; Barcelona Spain
| | - Luis Hernández
- Lymphoid Neoplasm Programme; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC); Barcelona Spain
| |
Collapse
|
|
28
|
Lockmer S, Østenstad B, Hagberg H, Holte H, Johansson AS, Wahlin BE, Wader KF, Steen CB, Meyer P, Maisenhølder M, Smedby KE, Brown P, Kimby E. Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up. J Clin Oncol 2018; 36:JCO1800262. [PMID: 30285560 DOI: 10.1200/jco.18.00262] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024] Open
Abstract
PURPOSE For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. METHODS Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations. RESULTS At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%. CONCLUSION Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.
Collapse
Affiliation(s)
- Sandra Lockmer
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Bjørn Østenstad
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Hans Hagberg
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Harald Holte
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Ann-Sofie Johansson
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Björn Engelbrekt Wahlin
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Karin Fahl Wader
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Chloé Beate Steen
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Peter Meyer
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Martin Maisenhølder
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Karin Ekström Smedby
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Peter Brown
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| | - Eva Kimby
- Sandra Lockmer, Björn Engelbrekt Wahlin, Karin Ekström Smedby, and Eva Kimby, Karolinska Institutet; Sandra Lockmer, Björn Engelbrekt Wahlin, and Karin Ekström Smedby, Karolinska University Hospital, Stockholm; Hans Hagberg, Academic Hospital, Uppsala; Ann-Sofie Johansson, Norrlands University Hospital, Umeå, Sweden; Bjørn Østenstad and Harald Holte, Oslo University Hospital; Chloé Beate Steen, University of Oslo, Oslo; Karin Fahl Wader, St Olavs Hospital, Trondheim; Peter Meyer, Stavanger University Hospital, Stavanger; Martin Maisenhølder, University Hospital of Northern Norway, Tromsø, Norway; and Peter Brown, Rigshospitalet, Copenhagen, Denmark
| |
Collapse
|
|
29
|
miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels. Blood 2018; 132:2389-2400. [PMID: 30213873 DOI: 10.1182/blood-2018-06-855502] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 09/05/2018] [Indexed: 12/12/2022] Open
Abstract
Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable clinical course. An unfavorable event in its course is histological transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma. Recent studies show that genetic aberrations of MYC or its overexpression are associated with FL transformation (tFL). However, the precise molecular mechanisms underlying tFL are unclear. Here we performed the first profiling of expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5 miRNAs as being differentially expressed. We focused on one of these miRNAs, namely miR-150, which was uniformly downmodulated in all examined tFLs (∼3.5-fold), and observed that high levels of MYC are responsible for repressing miR-150 in tFL by binding in its upstream region. This MYC-mediated repression of miR-150 in B cells is not dependent on LIN28A/B proteins, which influence the maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also demonstrated that low miR-150 levels in tFL lead to upregulation of its target, namely FOXP1 protein, which is a known positive regulator of cell survival, as well as B-cell receptor and NF-κB signaling in malignant B cells. We revealed that low levels of miR-150 and high levels of its target, FOXP1, are associated with shorter overall survival in FL and suggest that miR-150 could serve as a good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall, our study demonstrates the role of the MYC/miR-150/FOXP1 axis in malignant B cells as a determinant of FL aggressiveness and its high-grade transformation.
Collapse
|
|
30
|
Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis. LANCET HAEMATOLOGY 2018; 5:e359-e367. [PMID: 30078408 DOI: 10.1016/s2352-3026(18)30090-5] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/22/2018] [Accepted: 05/23/2018] [Indexed: 11/23/2022]
Abstract
BACKGROUND Histological transformation of follicular lymphoma to aggressive lymphoma is a serious event with a substantial effect on patient outcome. The aim of the Aristotle study was to assess the effect of rituximab on the risk of histological transformation and its outcome. METHODS 11 cooperative groups or institutions across Europe contributed data to this study. Eligible patients (≥18 years) had histologically confirmed follicular lymphoma grade 1, 2, or 3a, diagnosed between Jan 2, 1997, and Dec 20, 2013. Histological transformation was defined as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy. The primary endpoints were the cumulative hazard of histological transformation and survival after transformation. FINDINGS Information was available for 10 001 patients with follicular lymphoma, 8116 of whom were eligible for analysis. 509 histological transformations were reported. After a median follow-up of 87 months (range 1-221; 2·5-97·5th percentile 5-160), the 10-year cumulative hazard of histological transformation was 7·7% (95% CI 6·9-8·5). The 10-year cumulative hazard of histological transformation was 5·2% (95% CI 4·5-6·2) in patients who received rituximab and 8·7% (7·2-10·6) in those who did not (hazard ratio [HR] 0·73, 95% CI 0·58-0·90; p=0·004). The 10-year cumulative hazard of histological transformation was 5·9% (95% CI 5·0-7·0) for patients who received induction rituximab only and 3·6% (95% CI 2·3-5·5) for those treated with induction and maintenance rituximab (HR 0·55, 95% CI 0·37-0·81; p=0·003). This finding was confirmed in a multivariate analysis (p=0·016). 287 deaths were recorded in 509 patients with histological transformation, resulting in a 10-year survival after transformation of 32% (95% CI 26-38). Survival after transformation did not differ between patients not exposed to rituximab and those who received rituximab in induction only (HR 0·94, 95% CI 0·69-1·28; p=0·70), and those who received rituximab in induction and maintenance (0·96, 0·58-1·61; p=0·88). INTERPRETATION The risk of histological transformation as a first event can be significantly reduced by the use of rituximab. These findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituxumab. FUNDING Associazione Angela Serra per la Ricerca sul Cancro, European Lymphoma Institute, European Hematology Association Lymphoma Group, Fondazione Italiana Linfomi, Spanish Group of Lymphoma and Bone Marrow Transplantation.
Collapse
|
|
31
|
Casulo C, Nastoupil L, Fowler NH, Friedberg JW, Flowers CR. Unmet needs in the first-line treatment of follicular lymphoma. Ann Oncol 2018; 28:2094-2106. [PMID: 28430865 DOI: 10.1093/annonc/mdx189] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that ∼20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling. Prognostic methods to date have employed clinical parameters, genomic methods, and a wide assortment of biological and biochemical markers, but none so far has been able to adequately identify this high-risk population. Advances in the first-line treatment of FL with chemoimmunotherapy have led to a median progression-free survival (PFS) of approximately 7 years; creating a challenge in the development of clinical trials where PFS is a primary end point. A surrogate end point that accurately predicts PFS would allow for new treatments to reach patients with FL sooner, or lessen toxicity, time, and expense to those patients requiring little to no therapy. Quality of response to treatment may predict PFS and overall survival in FL; as such complete response rates, either alone or in conjunction with PET imaging or minimal residual disease negativity, are being studied as surrogates, with complete response at 30 months after induction providing the strongest surrogacy evidence to date. A better understanding of how to optimize quality of life in the context of this chronic illness is another important focus deserving of further study. Ongoing efforts to address these important unmet needs are herein discussed.
Collapse
Affiliation(s)
- C Casulo
- Department of Medicine, Hematology/Oncology, WIlmot Cancer Institute, University of Rochester Medical Center, Rochester, New York
| | - L Nastoupil
- Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston
| | - N H Fowler
- Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston
| | - J W Friedberg
- Department of Medicine, Hematology/Oncology, WIlmot Cancer Institute, University of Rochester Medical Center, Rochester, New York
| | - C R Flowers
- Department of Bone Marrow and Stem Cell Transplantation, Winship Cancer Institute, Emory University, Atlanta, USA
| |
Collapse
|
|
32
|
Minoia C, Zucca E, Conconi A. Novel acquisitions on biology and management of transformed follicular lymphoma. Hematol Oncol 2018; 36:617-623. [PMID: 29602222 DOI: 10.1002/hon.2508] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 02/07/2018] [Accepted: 02/08/2018] [Indexed: 11/07/2022]
Abstract
Follicular lymphoma (FL) generally has an indolent clinical course, but in some patients, a histological transformation (HT) into aggressive entities may take place and often lead to a poorer survival. The rituximab era has seen an improved outcome of FL, including those with HT. The current treatment strategies for transformed FL are based on immunochemotherapy for the cases with HT at the time of diagnosis or as the first event after watchful waiting. Patients transforming after prior treatment of FL usually benefit from autologous stem cell transplant. Unfortunately, early assessment of the transformation risk remains elusive. Recent studies delved the mechanisms of HT, showing that this is a complex process, resulting from a number of epigenetic and genetic lesions occurring in the tumour cell population as well as progressive changes in the tumour microenvironment. This novel knowledge has prompted clinical investigations on a variety of new therapeutic strategies.
Collapse
Affiliation(s)
- Carla Minoia
- Hematology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.,Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
| | - Emanuele Zucca
- Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.,Institute of Oncology Research (IOR), Bellinzona, Switzerland
| | - Annarita Conconi
- Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland.,Hematology Division, Ospedale degli Infermi, Biella, Italy
| |
Collapse
|
|
33
|
Link BK. Transformation of follicular lymphoma – Why does it happen and can it be prevented? Best Pract Res Clin Haematol 2018; 31:49-56. [DOI: 10.1016/j.beha.2017.10.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 10/23/2017] [Indexed: 02/02/2023]
|
|
34
|
Magnano L, Balagué O, Dlouhy I, Rovira J, Karube K, Pinyol M, Rivas-Delgado A, Costa D, Martínez-Trillos A, González-Farre B, Martínez-Pozo A, Giné E, Colomer D, Delgado J, Villamor N, Campo E, López-Guillermo A. Clinicobiological features and prognostic impact of diffuse large B-cell lymphoma component in the outcome of patients with previously untreated follicular lymphoma. Ann Oncol 2017; 28:2799-2805. [PMID: 29045517 DOI: 10.1093/annonc/mdx407] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023] Open
Abstract
BACKGROUND The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. PATIENTS AND METHODS All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. RESULTS The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. CONCLUSIONS The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.
Collapse
MESH Headings
- Aged
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Case-Control Studies
- Female
- Follow-Up Studies
- Humans
- Lymphoma, Follicular/complications
- Lymphoma, Follicular/drug therapy
- Lymphoma, Follicular/mortality
- Lymphoma, Follicular/pathology
- Lymphoma, Large B-Cell, Diffuse/complications
- Lymphoma, Large B-Cell, Diffuse/drug therapy
- Lymphoma, Large B-Cell, Diffuse/mortality
- Lymphoma, Large B-Cell, Diffuse/pathology
- Male
- Neoplasm Recurrence, Local/complications
- Neoplasm Recurrence, Local/drug therapy
- Neoplasm Recurrence, Local/mortality
- Neoplasm Recurrence, Local/pathology
- Prognosis
- Survival Rate
Collapse
Affiliation(s)
- L Magnano
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; Hematopathology Unit, Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona;; CIBERONC, Barcelona
| | - O Balagué
- CIBERONC, Barcelona;; Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - I Dlouhy
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona
| | - J Rovira
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona
| | - K Karube
- Department of Pathology and Cell Biology, Graduate School of Medicine, University of the Ryukyus;; Faculty of Medicine, University of the Ryukyus, Japan
| | - M Pinyol
- CIBERONC, Barcelona;; Genomics Unit, IDIBAPS, Barcelona, Spain
| | - A Rivas-Delgado
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona
| | - D Costa
- Hematopathology Unit, Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona;; CIBERONC, Barcelona
| | - A Martínez-Trillos
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona
| | - B González-Farre
- CIBERONC, Barcelona;; Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - A Martínez-Pozo
- CIBERONC, Barcelona;; Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - E Giné
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona
| | - D Colomer
- Hematopathology Unit, Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona;; CIBERONC, Barcelona
| | - J Delgado
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona
| | - N Villamor
- Hematopathology Unit, Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona;; CIBERONC, Barcelona
| | - E Campo
- Hematopathology Unit, Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona;; CIBERONC, Barcelona
| | - A López-Guillermo
- Department of Hematology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona;; CIBERONC, Barcelona;.
| |
Collapse
|
|
35
|
Fischer T, Zing NPC, Chiattone CS, Federico M, Luminari S. Transformed follicular lymphoma. Ann Hematol 2017; 97:17-29. [PMID: 29043381 DOI: 10.1007/s00277-017-3151-2] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 10/05/2017] [Indexed: 12/01/2022]
Abstract
Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment. Although t-FL is considered a devastating complication, as it is associated with treatment-refractory disease and a dismal outcome, recent data in the rituximab era have suggested that not only is the prognosis less severe than reported in the previous literature but the risk of transformation is also lower. Thus, this study aimed to review the most recent research on t-FL in an attempt to better understand the clinical meaning of transformation from FL to diffuse large B cell lymphoma (DLBCL) and the impact of current treatment strategies on the curability of this intriguing subentity of lymphoma.
Collapse
Affiliation(s)
- Thais Fischer
- Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil
| | | | | | | | - Stefano Luminari
- University of Modena and Reggio Emilia, Modena, Italy. .,Hematology Unit, Azienda Unità Sanitaria Locale IRCCS, Arcispedale Santa Maria Nuova IRCCS, viale Risorgimento n°80 42123, Reggio Emilia, Italy.
| |
Collapse
|
|
36
|
Sorigue M, Sancho JM. Current prognostic and predictive factors in follicular lymphoma. Ann Hematol 2017; 97:209-227. [PMID: 29032510 DOI: 10.1007/s00277-017-3154-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 10/09/2017] [Indexed: 12/27/2022]
Abstract
Follicular lymphoma (FL) is generally considered an indolent disorder. With modern day treatments, long remissions are often achieved both in the front-line and relapsed setting. However, a subset of patients has a more aggressive course and a worse outcome. Their identification is the main purpose of modern day prognostic tools. In this review, we attempt to summarize the evidence concerning prognostic and predictive factors in FL, including (1) pre-treatment factors, from baseline clinical characteristics and imaging tests to histological grade, the microenvironment and genomic abnormalities; (2) post-treatment factors, i.e., depth of response, measured both by imaging tests and minimal residual disease; (3) factors at relapse and duration of response; and (4) prognostic factors in histological transformation. We conclude that, despite the existence of numerous tools, the availability of some of them is still limited; they generally suffer from notable downsides, and most have unproven predictive value, thus having scarce bearing on the choice of regimen at present. However, with the technological and scientific developments of the last few years, the potential for these prognostic factors is promising, particularly in combination, which will probably, in time, help guide therapeutic decisions.
Collapse
MESH Headings
- Antineoplastic Combined Chemotherapy Protocols
- Bone Marrow/drug effects
- Bone Marrow/metabolism
- Bone Marrow/pathology
- Chromosomes, Human, Pair 14/chemistry
- Chromosomes, Human, Pair 18/chemistry
- Clinical Trials as Topic
- Disease-Free Survival
- Humans
- Lymphoma, Follicular/diagnostic imaging
- Lymphoma, Follicular/drug therapy
- Lymphoma, Follicular/genetics
- Lymphoma, Follicular/mortality
- Mutation
- Neoplasm Grading
- Neoplasm, Residual/diagnostic imaging
- Neoplasm, Residual/drug therapy
- Neoplasm, Residual/genetics
- Neoplasm, Residual/mortality
- Positron-Emission Tomography
- Prognosis
- Recurrence
- Risk Factors
- Translocation, Genetic
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
Collapse
Affiliation(s)
- Marc Sorigue
- Department of Hematology, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Ctra. Canyet, 08916, Badalona, Spain.
| | - Juan-Manuel Sancho
- Department of Hematology, ICO-Hospital Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autònoma de Barcelona, Ctra. Canyet, 08916, Badalona, Spain
| |
Collapse
|
|
37
|
Alonso-Álvarez S, Magnano L, Alcoceba M, Andrade-Campos M, Espinosa-Lara N, Rodríguez G, Mercadal S, Carro I, Sancho JM, Moreno M, Salar A, García-Pallarols F, Arranz R, Cannata J, Terol MJ, Teruel AI, Rodríguez A, Jiménez-Ubieto A, González de Villambrosia S, Bello JL, López L, Monsalvo S, Novelli S, de Cabo E, Infante MS, Pardal E, García-Álvarez M, Delgado J, González M, Martín A, López-Guillermo A, Caballero MD. Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group. Br J Haematol 2017; 178:699-708. [PMID: 28782811 DOI: 10.1111/bjh.14831] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 05/05/2017] [Indexed: 11/28/2022]
Abstract
The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.
Collapse
Affiliation(s)
- Sara Alonso-Álvarez
- Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Laura Magnano
- Hospital Clinic of Barcelona, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Miguel Alcoceba
- Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO).,CIBERONC, Spain
| | - Marcio Andrade-Campos
- Hospital Universitario Miguel Servet de Zaragoza - CIBERER, IIS-Aragón (ISCIII), Zaragoza, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Natalia Espinosa-Lara
- Hospital Universitario Miguel Servet de Zaragoza - CIBERER, IIS-Aragón (ISCIII), Zaragoza, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Guillermo Rodríguez
- Hospital Virgen del Rocío Sevilla, Sevilla, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Santiago Mercadal
- Instituto Catalán de Oncología (ICO) Duran i Reynals, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Itziar Carro
- Instituto Catalán de Oncología (ICO) Duran i Reynals, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Juan M Sancho
- Instituto Catalán de Oncología (ICO-IJC) German Trias i Pujol, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Miriam Moreno
- Instituto Catalán de Oncología (ICO-IJC) German Trias i Pujol, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Antonio Salar
- Hospital del Mar, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Francesc García-Pallarols
- Hospital del Mar, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Reyes Arranz
- Hospital La Princesa, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Jimena Cannata
- Hospital La Princesa, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - María José Terol
- Hospital Clínico, Valencia, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Ana I Teruel
- Hospital Clínico, Valencia, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Antonia Rodríguez
- Hospital 12 de Octubre, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Ana Jiménez-Ubieto
- Hospital 12 de Octubre, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Sonia González de Villambrosia
- Hospital Marqués de Valdecilla, Santander, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - José L Bello
- Hospital Universitario de Santiago de Compostela, Santiago de Compostela, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Lourdes López
- Hospital MD Anderson, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Silvia Monsalvo
- Hospital Fundación Jiménez Díaz, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Silvana Novelli
- Hospital Sant Pau, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Erik de Cabo
- Hospital del Bierzo, Ponferrada, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - María S Infante
- Hospital Infanta Leonor, Madrid, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Emilia Pardal
- Hospital Virgen del Puerto, Plasencia, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - María García-Álvarez
- Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO)
| | - Julio Delgado
- Hospital Clinic of Barcelona, Barcelona, Spain.,CIBERONC, Spain
| | - Marcos González
- Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO).,CIBERONC, Spain
| | - Alejandro Martín
- Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO).,CIBERONC, Spain
| | - Armando López-Guillermo
- Hospital Clinic of Barcelona, Barcelona, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO).,CIBERONC, Spain
| | - María D Caballero
- Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.,Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea (GELTAMO).,CIBERONC, Spain
| |
Collapse
|
|
38
|
Can histologic transformation of follicular lymphoma be predicted and prevented? Blood 2017; 130:258-266. [DOI: 10.1182/blood-2017-03-691345] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 04/06/2017] [Indexed: 12/28/2022] Open
Abstract
Abstract
Transformation to aggressive lymphoma is a critical event in the clinical course of follicular lymphoma (FL) patients. Yet, it is a challenge to reliably predict transformation at the time of diagnosis. Understanding the risk of transformation would be useful for guiding and monitoring patients, as well as for evaluating novel treatment strategies that could potentially prevent transformation. Herein, we review the contribution of clinical, pathological, and genetic risk factors to transformation. Patients with multiple clinical high-risk factors are at elevated risk of transformation but we are currently lacking a prognostic index that would specifically address transformation rather than disease progression or overall survival. From the biological standpoint, multiple studies have correlated individual biomarkers with transformation. However, accurate prediction of this event is currently hampered by our limited knowledge of the evolutionary pathways leading to transformation, as well as the scarcity of comprehensive, large-scale studies that assess both the genomic landscape of alterations within tumor cells and the composition of the microenvironment. Liquid biopsies hold great promise for achieving precision medicine. Indeed, mutations detected within circulating tumor DNA may be a better reflection of the inherent intratumoral heterogeneity than the biopsy of a single site. Last, we will assess whether evidence exists in the literature that transformation might be prevented altogether, based on the choice of therapy for FL.
Collapse
|
|
39
|
Mendez M, Torrente M, Provencio M. Follicular lymphomas and their transformation: Past and current research. Expert Rev Hematol 2017; 10:515-524. [PMID: 28480766 DOI: 10.1080/17474086.2017.1326812] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). Histological transformation (HT) refers to the evolution of a clinically indolent NHL to a clinically aggressive one, defined as those lymphomas in which survival is limited to a few months when untreated. Areas covered: HT is associated with rapid progression of lymphadenopathy, infiltration of extranodal sites, development of systemic symptoms, and elevated serum level of lactate dehydrogenase (LDH). It is frequently related to a poor prognosis, and the median survival after transformation is less than 2 years. Transformation to diffuse large B cell lymphoma (DLBCL) in patients with FL occurs at an annual rate of approximately 3% for the first 15 years, after which the risk of HT falls for reasons that remain unclear. Expert commentary: Although it has long been assumed that transformation reflects the emergence of an aggressive subclone of cells from the primary FL, recent studies suggest that FL transformation might also arise by divergent evolution from a more immature common progenitor cell. Studies on genomic changes and DNA sequencing have shed some light onto the process of transformation. Nowadays, we know that HT is a complex process where several molecular pathways are involved.
Collapse
Affiliation(s)
- Miriam Mendez
- a Medical Oncology Department , Hospital Universitario Puerta de Hierro-Majadahonda , Madrid , Spain
| | - Maria Torrente
- a Medical Oncology Department , Hospital Universitario Puerta de Hierro-Majadahonda , Madrid , Spain
| | - Mariano Provencio
- a Medical Oncology Department , Hospital Universitario Puerta de Hierro-Majadahonda , Madrid , Spain
| |
Collapse
|
|
40
|
Bischin AM, Dorer R, Aboulafia DM. Transformation of Follicular Lymphoma to a High-Grade B-Cell Lymphoma With MYC and BCL2 Translocations and Overlapping Features of Burkitt Lymphoma and Acute Lymphoblastic Leukemia: A Case Report and Literature Review. Clin Med Insights Blood Disord 2017; 10:1179545X17692544. [PMID: 28579851 PMCID: PMC5428247 DOI: 10.1177/1179545x17692544] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 01/16/2017] [Indexed: 12/16/2022]
Abstract
Most commonly, histologic transformation (HT) from follicular lymphoma (FL) manifests as a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). Less frequently, HT may result in a high-grade B-cell lymphoma (HGBL) with MYC and B-cell lymphoma protein 2 (BCL2) and/or BCL6 gene rearrangements, also known as “double-hit” or “triple-hit” lymphomas. In the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms, the category B-cell lymphoma, unclassifiable was eliminated due to its vague criteria and limiting diagnostic benefit. Instead, the WHO introduced the HGBL category, characterized by MYC and BCL2 and/or BCL6 rearrangements. Cases that present as an intermediate phenotype of DLBCL and Burkitt lymphoma (BL) will fall within this HGBL category. Very rarely, HT results in both the intermediate DLBCL and BL phenotypes and exhibits lymphoblastic features, in which case the WHO recommends that this morphologic appearance should be noted. In comparison with de novo patients with DLBCL, NOS, those with MYC and BCL2 and/or BCL6 gene rearrangements have a worse prognosis. A 63-year-old woman presented with left neck adenopathy. Laboratory assessments, including complete blood count, complete metabolic panel, serum lactate dehydrogenase, and β2-microglobulin, were all normal. A whole-body computerized tomographic (CT) scan revealed diffuse adenopathy above and below the diaphragm. An excisional node biopsy showed grade 3A nodular FL. The Ki67 labeling index was 40% to 50%. A bone marrow biopsy showed a small focus of paratrabecular CD20+ lymphoid aggregates. She received 6 cycles of bendamustine (90 mg/m2 on days +1 and +2) and rituximab (375 mg/m2 on day +2), with each cycle delivered every 4 weeks. A follow-up CT scan at completion of therapy showed a partial response with resolution of axillary adenopathy and a dramatic shrinkage of the large retroperitoneal nodes. After 18 months, she had crampy abdominal pain in the absence of B symptoms. Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with CT (18F-FDG PET/CT) scan showed widespread adenopathy, diffuse splenic involvement, and substantial marrow involvement. Biopsy of a 2.4-cm right axillary node (SUVmax of 16.1) showed involvement by grade 3A FL with a predominant nodular pattern of growth. A bone marrow biopsy once again showed only a small focus of FL. She received idelalisib (150 mg twice daily) and rituximab (375 mg/m2, monthly) beginning May 2015. After 4 cycles, a repeat CT scan showed a complete radiographic response. Idelalisib was subsequently held while she received corticosteroids for immune-mediated colitis. A month later, she restarted idelalisib with a 50% dose reduction. After 2 weeks, she returned to clinic complaining of bilateral hip and low lumbar discomfort but no B symptoms. A restaging 18F-FDG PET/CT in January 2016 showed dramatic marrow uptake. A bone marrow aspirate showed sheets of tumor cells representing a spectrum from intermediate-sized cells with lymphoblastic features to very large atypical cells with multiple nucleoli. Two distinct histologies were present; one remained consistent with the patient’s known FL with a predominant nodular pattern and the other consistent with HT (the large atypical cells expressed PAX5, CD10, BCL2, and c-MYC and were negative for CD20, MPO, CD34, CD30, and BCL6). Focal areas showed faint, heterogeneous expression of terminal deoxynucleotidyl transferase best seen on the clot section. Ki67 proliferation index was high (4+/4). Fluorescence in situ hybridization analysis showed 2 populations with MYC amplification and/or rearrangement and no evidence of BCL6 rearrangement; a karyotype analysis showed a complex abnormal female karyotype with t(14;18) and multiple structural and numerical abnormalities. She started dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with concomitant prophylactic intrathecal methotrexate and cytarabine. She had but a short-lived response before dying in hospice from progressive lymphoma. Whether idelalisib could provide a microenvironment for selection of more aggressive clones needs to be addressed. Our patient’s clinical course is confounded by the incorporation of idelalisib while being further complicated by the complexity of HT and the mechanisms in which first-line chemotherapy regimens affect double-hit lymphoma.
Collapse
Affiliation(s)
- Alina M Bischin
- School of Medicine, University of Washington, Seattle, WA, USA
| | - Russell Dorer
- Department of Pathology, Virginia Mason Medical Center, Seattle, WA, USA
| | - David M Aboulafia
- Department of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA, USA.,Division of Hematology, School of Medicine, University of Washington, Seattle, WA, USA
| |
Collapse
|
|
41
|
Magnano L, Montoto S, González-Barca E, Briones J, Sancho JM, Muntañola A, Salar A, Besalduch J, Escoda L, Moreno C, Domingo-Domenech E, Estany C, Oriol A, Altés A, Pedro C, Gardella S, Asensio A, Vivancos P, Fernández de Sevilla A, Ribera JM, Colomer D, Campo E, López-Guillermo A. Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial. Ann Hematol 2017; 96:639-646. [DOI: 10.1007/s00277-017-2920-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 12/29/2016] [Indexed: 11/25/2022]
|
|
42
|
Gleeson M, Hawkes EA, Peckitt C, Wotherspoon A, Attygalle A, Sharma B, Du Y, Ethell M, Potter M, Dearden C, Horwich A, Chau I, Cunningham D. Outcomes for transformed follicular lymphoma in the rituximab era: the Royal Marsden experience 2003–2013. Leuk Lymphoma 2016; 58:1805-1813. [DOI: 10.1080/10428194.2016.1265114] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Mary Gleeson
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | - Eliza A. Hawkes
- Department of Oncology and Clinical Haematology, Austin Health, Heidelberg, Melbourne, Australia
- Eastern Health, Melbourne, Australia
| | - Clare Peckitt
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | | | - Ayoma Attygalle
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | | | - Yong Du
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | - Mark Ethell
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | - Mike Potter
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | - Claire Dearden
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | - Alan Horwich
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | - Ian Chau
- The Royal Marsden Hospital, London and Surrey, United Kingdom
| | | |
Collapse
|
|
43
|
|
|
44
|
Systemic Front Line Therapy of Follicular Lymphoma: When, to Whom and How. Mediterr J Hematol Infect Dis 2016; 8:e2016062. [PMID: 27872742 PMCID: PMC5111519 DOI: 10.4084/mjhid.2016.062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 11/04/2016] [Indexed: 02/06/2023] Open
Abstract
The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can’t be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of “naked” or “conjugated” anti-CD20 monoclonal antibodies as a single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role in the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs, and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.
Collapse
|
|
45
|
Yun S, Vincelette ND, Abraham I, Puvvada S, Anwer F. Outcome Comparison of Allogeneic versus Autologous Stem Cell Transplantation in Transformed Low-Grade Lymphoid Malignancies: A Systematic Review and Pooled Analysis of Comparative Studies. Acta Haematol 2016; 136:244-255. [PMID: 27802434 DOI: 10.1159/000449031] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 08/09/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND Some patients with low-grade lymphoid malignancies develop transformed disease, requiring stem cell transplantation (SCT). SCT outcomes in transformed low-grade lymphoid malignancies may differ from those of nontransformed disease or other aggressive non-Hodgkin lymphomas. We conducted a pooled analysis of the clinical outcomes of allogeneic versus high-dose therapy (HDT) with autologous SCT in adult patients with transformed low-grade lymphoid malignancies. METHODS A PubMed, EMBASE, and Cochrane search yielded 4 comparative studies reporting allogeneic versus HDT with autologous SCT outcomes in adults (age ≥18) with transformed low-grade lymphoid malignancies, including follicular, chronic/small lymphocytic, and marginal zone lymphoma. Risk ratio (RR) and 95% CI were calculated using random-effects models. RESULTS Rates for overall survival (OS) were 51.0 versus 69.5% (RR = 1.55, 95% CI 1.19-2.02, p = 0.001), rates of relapse were 37.3 versus 35.3% (RR = 1.04, 95% CI 0.70-1.55, p = 0.84), and rates of transplant-related mortality (TRM) were 33.3 versus 7.2% (RR = 4.52, 95% CI 2.75-7.43, p < 0.00001) for allogeneic versus autologous SCT. Previous rituximab treatment, reduced intensity conditioning regimen prior to SCT, or original pathology had no prognostic impact. CONCLUSION HDT followed by autologous SCT was associated with lower TRM and a better OS, but there was no difference in relapse versus allogeneic SCT. Autologous SCT may be the better therapeutic option, considering the second chance of allogeneic SCT in the case of relapse.
Collapse
Affiliation(s)
- Seongseok Yun
- Department of Hematology and Oncology, H. Lee Moffitt Cancer Center, Tampa, Fla., USA
| | | | | | | | | |
Collapse
|
|
46
|
Iwamuro M, Kondo E, Takata K, Yoshino T, Okada H. Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup. World J Gastroenterol 2016; 22:1674-83. [PMID: 26819532 PMCID: PMC4721998 DOI: 10.3748/wjg.v22.i4.1674] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/28/2015] [Accepted: 10/12/2015] [Indexed: 02/06/2023] Open
Abstract
Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease's endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis.
Collapse
|
|
47
|
Abstract
Abstract
Histologic transformation (HT) is a frequent event in the clinical course of patients with indolent lymphoma. Most of the available data in the literature comes from studies on transformation of follicular lymphoma (FL), as this is the most common indolent lymphoma; however, HT is also well documented following small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL), lymphoplasmacytic lymphoma (LPL), or marginal zone lymphoma (MZL), amongst other types of lymphoma, albeit most of the studies on transformation in these subtypes are case reports or short series. The outcome of patients with HT has traditionally been considered dismal with a median overall survival (OS) of around 1 year in most of the published studies. This prompted many authors to include stem cell transplant (SCT) as part of the treatment strategy for young and fit patients with HT. However, recent articles suggest that the outcome of patients with transformed lymphoma might be improving, questioning the need for such intensive therapies. The management of patients with HT is challenged by the heterogeneity of the population in terms of previous number and type of therapy lines and from their exclusion from prospective clinical trials. This review will examine whether the advent of new therapies has impacted on the prognosis of HT and on current treatment strategies.
Collapse
|
|
48
|
Cell of origin of transformed follicular lymphoma. Blood 2015; 126:2118-27. [PMID: 26307535 DOI: 10.1182/blood-2015-06-649905] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 08/20/2015] [Indexed: 01/10/2023] Open
Abstract
Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.
Collapse
|
|
49
|
Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS). Blood 2015; 126:851-7. [PMID: 26105149 DOI: 10.1182/blood-2015-01-621375] [Citation(s) in RCA: 156] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 06/07/2015] [Indexed: 11/20/2022] Open
Abstract
We assessed the incidence, prognostic features, and outcomes associated with transformation of follicular lymphoma (FL) among 2652 evaluable patients prospectively enrolled in the National LymphoCare Study. At a median follow-up of 6.8 years, 379/2652 (14.3%) patients transformed following the initial FL diagnosis, including 147 pathologically confirmed and 232 clinically suspected cases. Eastern Cancer Oncology Group performance status >1, extranodal sites >1, elevated lactate dehydrogenase, and B symptoms at diagnosis were associated with transformation risk. Relative to observation, patients initiating treatment at diagnosis had a reduced risk of transformation (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.46-0.75). The risk of transformation was similar in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone compared with rituximab, cyclophosphamide, vincristine, and prednisone (adjusted HR, 0.94; 95% CI, 0.62-1.42). Maintenance rituximab was associated with reduced transformation risk (HR, 0.67; 95% CI, 0.46-0.97). Five-year survival from diagnosis was significantly worse for patients with vs without transformation (75%, 95% CI, 70-79 vs 85%, 95% CI, 83-86). The median overall survival post-transformation was 5 years. Forty-seven patients with evidence of transformation at the time of diagnosis shared similar prognostic factors and survival rates to those without transformation. Improved outcomes for transformation in the modern era are suggested by this observational study. This trial is registered at www.clinicaltrials.gov as #NCT00097565.
Collapse
|
|
50
|
Gribben JG. XV. Clinical aspects of transformed lymphoma. Hematol Oncol 2015; 33 Suppl 1:80-3. [PMID: 26062061 DOI: 10.1002/hon.2223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- John G Gribben
- Barts Cancer Institute, St Bartholomew's Hospital, Queen Mary University of London, London, UK
| |
Collapse
|