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1
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Carneiro AP, Reis CF, Morari EC, Maia YCP, Nascimento R, Bonatto JMC, de Souza MA, Goulart LR, Ward LS. A putative OTU domain-containing protein 1 deubiquitinating enzyme is differentially expressed in thyroid cancer and identifies less-aggressive tumours. Br J Cancer 2014; 111:551-8. [PMID: 24937664 PMCID: PMC4119988 DOI: 10.1038/bjc.2014.331] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Revised: 03/20/2014] [Accepted: 05/15/2014] [Indexed: 12/22/2022] Open
Abstract
Background: This study aimed to identify novel biomarkers for thyroid carcinoma diagnosis and prognosis. Methods: We have constructed a human single-chain variable fragment (scFv) antibody library that was selected against tumour thyroid cells using the BRASIL method (biopanning and rapid analysis of selective interactive ligands) and phage display technology. Results: One highly reactive clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was confirmed by ELISA, which was further tested against a tissue microarray that comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18 normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Conclusions: The strategy of screening and identifying a cell-surface-binding antibody against thyroid tissues was highly effective and resulted in a useful biomarker that recognises malignancy among thyroid nodules and may help identify lower-risk cases that can benefit from less-aggressive management.
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Affiliation(s)
- A P Carneiro
- Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), Campinas, SP, Brazil
| | - C F Reis
- Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), Campinas, SP, Brazil
| | - E C Morari
- Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), Campinas, SP, Brazil
| | - Y C P Maia
- Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry (Ingeb), Federal University of Uberlandia, Uberlandia, MG, Brazil
| | - R Nascimento
- Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry (Ingeb), Federal University of Uberlandia, Uberlandia, MG, Brazil
| | - J M C Bonatto
- Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, Brazil
| | - M A de Souza
- Laboratory of Molecular Biology, Federal University of Uberlandia, Institute of Biomedical Sciences, Uberlandia, MG, Brazil
| | - L R Goulart
- 1] Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry (Ingeb), Federal University of Uberlandia, Uberlandia, MG, Brazil [2] Department of Medical Microbiology and Immunology, University of California-Davis, Davis, CA, USA
| | - L S Ward
- Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences (FCM), University of Campinas (Unicamp), Campinas, SP, Brazil
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2
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Antibody phage display libraries: contributions to oncology. Int J Mol Sci 2012; 13:5420-5440. [PMID: 22754305 PMCID: PMC3382779 DOI: 10.3390/ijms13055420] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Revised: 04/05/2012] [Accepted: 04/24/2012] [Indexed: 12/16/2022] Open
Abstract
Since the advent of phage display technology, dating back to 1985, antibody libraries displayed on filamentous phage surfaces have been used to identify specific binders for many different purposes, including the recognition of tumors. Phage display represents a high-throughput technique for screening billions of random fusion antibodies against virtually any target on the surface or inside cancer cells, or even soluble markers found in patient serum. Many phage display derived binders targeting important tumor markers have been identified. Selection directed to tumoral cells’ surfaces lead to the identification of unknown tumoral markers. Also the improvement of methods that require smaller amounts of cells has opened the possibility to use this approach on patient samples. Robust techniques combining an antibody library displayed on the phage surface and protein microarray allowed the identification of auto antibodies recognized by patient sera. Many Ab molecules directly or indirectly targeting angiogenesis have been identified, and one of them, ramucirumab, has been tested in 27 phase I–III clinical trials in a broad array of cancers. Examples of such antibodies will be discussed here with emphasis on those used as probes for molecular imaging and other clinical trials.
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3
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Tsutsumi Y, Yamamoto Y, Tanaka J, Asaka M, Imamura M, Masauzi N. Prevention of hepatitis B virus reactivation under rituximab therapy. Immunotherapy 2011; 1:1053-61. [PMID: 20635919 DOI: 10.2217/imt.09.59] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Rituximab is a useful drug for the treatment of B-cell non-Hodgkin's lymphoma, and its use has been extended to other diseases such as idiopathic thrombocytopenic purpura and chronic rheumatoid arthritis. One serious complication associated with rituximab use is reactivation of hepatitis B virus, and the search for methods to prevent this occurrence has resulted in a rapid accumulation of knowledge in recent years. In this review, we will discuss case studies from our group, as well as other groups, and outline current knowledge on the topic together with issues that remain to be resolved.
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Affiliation(s)
- Yutaka Tsutsumi
- Department of Internal Medicine, Hakodate Municipal Hospital 1-10-1, Minato-cho, Hakodate 041-8680, Japan.
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Vega MI, Huerta-Yepez S, Martinez-Paniagua M, Martinez-Miguel B, Hernandez-Pando R, González-Bonilla CR, Chinn P, Hanna N, Hariharan K, Jazirehi AR, Bonavida B. Rituximab-mediated cell signaling and chemo/immuno-sensitization of drug-resistant B-NHL is independent of its Fc functions. Clin Cancer Res 2009; 15:6582-94. [PMID: 19861448 DOI: 10.1158/1078-0432.ccr-09-1234] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined with chemotherapy, is used in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab binds to CD20 and inhibits intracellular survival/growth pathways leading to chemo/immunosensitization of tumor cells in vitro. The contribution of rituximab Fc-FcR interaction in signaling is not known. This study examined the role of Fc-FcR interactions in rituximab-induced signaling using rituximab (Fab')(2) fragments as well as rituximab devoid of the CH2 Fc-binding domain (CH2(-)). EXPERIMENTAL DESIGN Rituximab (CH2(-)) and rituximab (Fab')(2) were tested for their activity on B-NHL cell lines. Cell signaling and sensitization to chemotherapy and immunotherapy were examined. The in vitro studies were validated in mice bearing tumor xenografts. RESULTS Although the modified antibodies were defective in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity functions, they retained all other biological activities such as inhibition of cell proliferation, induction of cell aggregation, and apoptosis induction. In addition, similar to rituximab, the modified antibodies inhibited the activity of cell survival/growth pathways and their associated transcription factors (e.g., NF-kappaB, YY1, SP-1), and signal transducers and activators of transcription 3 (STAT-3), and downregulated the expression of antiapoptotic gene products, such as Bcl-2/Bcl(xl), which regulate drug resistance. The modified antibodies, similar to rituximab, sensitized resistant B-NHL cells to both CDDP and Fas ligand-induced apoptosis. Furthermore, treatment of nude mice bearing Raji tumor cell xenografts with the combination of rituximab (Fab')(2) or rituximab and CDDP resulted in similar and significant inhibition of tumor growth. CONCLUSION These findings reveal that rituximab-mediated inhibition of intracellular signaling pathways and leading to chemo/immuno-sensitization of resistant B-NHL is Fc independent.
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Affiliation(s)
- Mario I Vega
- Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1747, USA
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5
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Schöllkopf C, Kjeldsen L, Bjerrum OW, Mourits-Andersen HT, Nielsen JL, Christensen BE, Jensen BA, Pedersen BB, Taaning EB, Klausen TW, Birgens H. Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma 2009; 47:253-60. [PMID: 16321854 DOI: 10.1080/10428190500286481] [Citation(s) in RCA: 99] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Chronic cold agglutinin disease (CAD) is an acquired autoimmune hemolytic anemia. Previous therapeutic modalities, including alkylating cytostatics, interferon and prednisolone, have been disappointing. However, several case reports and small-scaled studies have demonstrated promising results after treatment with rituximab. We performed a phase II multicentre trial to investigate the effect of rituximab in CAD, including 20 patients studied from October 2002 until April 2003. Thirteen patients had idiopathic CAD and seven patients had CAD associated with a malignant B-cell lymphoproliferative disease. Rituximab was given in doses of 375 mg/m(2) at days 1, 8, 15 and 22. Sixteen patients were followed up for at least 48 weeks. Four patients were excluded after 8, 16, 23 and 28 weeks for reasons unrelated to CAD. Nine patients (45%) responded to the treatment, one with complete response (CR), and eight with partial response. Eight patients relapsed, one patient was still in remission at the end of follow-up. There were no serious rituximab-related side-effects. Our study confirms previous findings of a favourable effect of rituximab in patients with CAD. However, few patients will obtain CR and, in most patients, the effect will be transient.
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6
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Asfour IA, Fayek M, Raouf S, Soliman M, Hegab HM, El-Desoky H, Saleh R, Moussa MAR. The impact of high-dose sodium selenite therapy on Bcl-2 expression in adult non-Hodgkin's lymphoma patients: correlation with response and survival. Biol Trace Elem Res 2007; 120:1-10. [PMID: 17916949 DOI: 10.1007/s12011-007-0029-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2006] [Revised: 02/27/2007] [Accepted: 03/02/2007] [Indexed: 12/14/2022]
Abstract
The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the expression of Bcl-2 in patients with non-Hodgkin's lymphoma (NHL). Fifty patients with newly diagnosed NHL were randomly divided into two groups. Group A-I received standard chemotherapy whereas group A-II received adjuvant sodium selenite 0.2 mg kg-1 day-1 for 30 days in addition to chemotherapy. Enzyme-linked immunosorbent assay was used to assess Bcl-2 at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant decline of Bcl-2 level after therapy in group A-II (8.6 +/- 6.9 ng/ml vs 3 6.9 +/- 7.9 ng/ml, P < 0.05). Also, complete response reached 60% in group A-II compared to 40% in group A-I. Significant increase in CD4/CD8 ratio was noticed in group A-II compared to group A-I after therapy (1.45 +/- 0.36 vs 1.10 +/- 0.28 p 0.04). Overall survival time in months was significantly longer in complete remission patients in group A-II (21.87 +/- 1.41) compared to group A-I (19.70 +/- 1.95) (p = 0.01). It is concluded that sodium selenite administration at the dosage and duration chosen acts as a down regulator of Bcl-2 and improves clinical outcome.
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Affiliation(s)
- Inas A Asfour
- Clinical Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Ain Shams University Hospital, Cairo, Egypt
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7
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Goodlad JR, Batstone PJ, Hamilton DA, Kernohan NM, Levison DA, White JM. BCL2 gene abnormalities define distinct clinical subsets of follicular lymphoma. Histopathology 2006; 49:229-41. [PMID: 16918969 DOI: 10.1111/j.1365-2559.2006.02501.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
AIMS Follicular lymphoma (FL) arising primarily in the skin has recently been proposed as a distinct entity on the basis of a low incidence of t(14;18)(q32;q21) and bcl-2 expression, with a very high percentage of patients surviving more than 5 years. However, cases of t(14;18)(q32;q21)-positive primary cutaneous FL (PCFL) and examples of t(14;18)(q32;q21)-negative FL at nodal and other extranodal sites, are well documented. The aim of this study was to test the hypothesis that there is a subtype of FL lacking t(14;18)(q32;q21), which preferentially involves certain sites but is not restricted by anatomical location. METHODS AND RESULTS A cohort of 47 stage 1 FL was stratified according to the presence or absence of t(14;18)(q32;q21) using conventional cytogenetics, polymerase chain reaction and interphase fluorescence in situ hybridization. Compared with t(14;18)(q32;q21)-positive cases, FL lacking the translocation were less likely to express CD10 or bcl-2 (P<0.01), made up a significantly greater proportion of cases arising at extranodal sites (P<0.001) and had a significantly better overall and disease-specific 5-year survival (P<0.01). CONCLUSIONS These results support the concept of a subtype of FL lacking t(14;18)(q32;q21), characterized by low-intensity bcl-2 expression, a predilection for extranodal sites, particularly the skin, and a more favourable outcome than t(14;18)(q32;q21)-positive FL.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Chromosome Aberrations
- Chromosomes, Human, Pair 14/genetics
- Chromosomes, Human, Pair 18/genetics
- Female
- Genes, bcl-2
- Humans
- In Situ Hybridization, Fluorescence
- Lymphoma, Follicular/classification
- Lymphoma, Follicular/genetics
- Lymphoma, Follicular/mortality
- Male
- Middle Aged
- Neprilysin/biosynthesis
- Polymerase Chain Reaction
- Prognosis
- Proto-Oncogene Proteins c-bcl-2/biosynthesis
- Survival Analysis
- Translocation, Genetic
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Affiliation(s)
- J R Goodlad
- Department of Pathology, Western General Hospital, Edinburgh, and Division of Pathology and Neuroscience, University of Dundee, UK.
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Tsutsumi Y, Kanamori H, Mori A, Tanaka J, Asaka M, Imamura M, Masauzi N. Reactivation of hepatitis B virus with rituximab. Expert Opin Drug Saf 2006; 4:599-608. [PMID: 15934864 DOI: 10.1517/14740338.4.3.599] [Citation(s) in RCA: 106] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Rituximab has become a useful drug for the treatment of non-Hodgkin's lymphoma (NHL) and such autoimmune diseases as idiopathic thrombocytopenic purpura and rheumatoid arthritis. When combined with cytotoxic agents, rituximab showed synergistic effects for the treatment of NHL. In such treatment, hepatitis B virus (HBV) reactivation is a crucial complication when patients are treated with immunosuppressive or chemotherapeutic agents. Despite its treatment efficacy, several studies have pointed out unusual viral infections after its administration that resulted in fatal hepatitis due to HBV reactivation. In the cases at the authors' institute, the authors analysed the kinetics of HBV antibodies, HBV-reactivation timing, and the prophylactic efficacy of lamivudine. The authors reviewed their cases and the previous literature to clarify the characteristics of HBV-reactivated patients who were administered rituximab.
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Affiliation(s)
- Yutaka Tsutsumi
- Department of Internal Medicine, Hakodate Municipal Hospital, Hakodate 041-8680, Japan.
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9
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Cronin DP, Harlan LC, Clegg LX, Stevens JL, Yuan G, Davis TA. Patterns of care in a population-based random sample of patients diagnosed with non-Hodgkin's lymphoma. Hematol Oncol 2006; 23:73-81. [PMID: 16170828 DOI: 10.1002/hon.747] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
New therapies have enhanced treatment of non-Hodgkin's lymphoma (NHL), but extent of treatment use in community practice is unknown. We conducted a population-based study of NHL patients diagnosed in 1999 with histologically confirmed NHL (n = 947) residing in areas covered by the Surveillance, Epidemiology, and End Results program. We performed analyses to study factors associated with receipt of chemotherapy, radiation, and rituximab, and examine factors associated with mortality. Most patients presented with B-cell lymphoma (n = 828). Approximately 20% of patients received no therapy, over 60% received chemotherapy, and 12% received rituximab, alone or in combination. Patients aged 75 +, and males were less likely to have received chemotherapy (p = 0.01). There were no significant associations between receipt of rituximab and the factors analyzed. Patients who presented with B-symptoms or unknown B-symptom status were less likely to receive radiation (OR = 0.32 and 0.47, respectively, p = 0.0002) than asymptomatic patients. Cause-specific and all-cause mortality were significantly associated with patient age, race/ethnicity, gender, marital status, co-morbid conditions, and histological subgroup. Hispanic and African-Americans, patients age 75 +, males, unmarried patients, or patients with B-symptoms had higher risk of death from NHL and all-cause (p < 0.01). This is the first population-based study examining therapy received for many histological subtypes of NHL.
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Affiliation(s)
- Deirdre P Cronin
- National Cancer Registry Ireland, Elm Court, Boreenmanna Rd., Cork, Ireland.
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Gokhale AS, Mayadev J, Pohlman B, Macklis RM. Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy. Int J Radiat Oncol Biol Phys 2005; 63:194-201. [PMID: 16111589 DOI: 10.1016/j.ijrobp.2005.01.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2004] [Revised: 01/11/2005] [Accepted: 01/12/2005] [Indexed: 11/13/2022]
Abstract
PURPOSE To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. METHODS AND MATERIALS Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. RESULTS Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of "bulky" (maximal diameter > or = 5 cm) disease displayed evidence of progression vs. 28% (26/93) of "nonbulky" disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. CONCLUSION We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.
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Affiliation(s)
- Abhay S Gokhale
- Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
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Hicks RJ, Mac Manus MP, Seymour JF. Initial Staging of Lymphoma With Positron Emission Tomography and Computed Tomography. Semin Nucl Med 2005; 35:165-75. [PMID: 16098290 DOI: 10.1053/j.semnuclmed.2005.02.003] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Lymphomas represent a diverse range of diseases with manifold presentations, outlook, and therapeutic approaches. Key to the modern management of lymphoma is accurate delineation of the extent of disease. The inability of computed tomography (CT) to identify the involvement of nonenlarged nodes and its relatively poor sensitivity in the detection of extra-nodal sites of involvement limit the performance of noninvasive staging techniques. Functional imaging techniques such as Ga-67 scintigraphy have been used for many years to improve the evaluation of patients with lymphoma. While providing complementary information to CT in many clinical settings, functional imaging has never had sufficient accuracy or localizing ability to seriously challenge conventional primary staging paradigms. (18)F-Fluorodeoxyglucose positron emission tomography (FDG PET), however, has been demonstrated to have both higher sensitivity and specificity than CT in many comparative series. Now that this technology also can be performed at the same time as structural imaging in the form of hybrid PET/CT devices, clinicians are rethinking the methods used to select, plan, and monitor therapy of lymphoma patients. In our institution, FDG PET/CT has become the preferred initial staging tool for patients with lymphoma.
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Affiliation(s)
- Rodney J Hicks
- Centre for Molecular Imaging, Peter MacCallum Cancer Centre, 12 Cathedral Place, East Melbourne, Victoria 3002, Australia.
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Current Awareness in Hematological Oncology. Hematol Oncol 2005. [DOI: 10.1002/hon.720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Fulignati C, Pantaleo P, Cipriani G, Turrini M, Nicastro R, Mazzanti R, Neri B. An uncommon clinical presentation of retroperitoneal non-Hodgkin lymphoma successfully treated with chemotherapy: A case report. World J Gastroenterol 2005; 11:3151-5. [PMID: 15918208 PMCID: PMC4305858 DOI: 10.3748/wjg.v11.i20.3151] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We report the case of a patient affected by an extra-nodal non-Hodgkin lymphoma presenting as a unique, large retroperitoneal mass with an unusual clinical presentation mimicking gastric peptic or neoplastic disease. The patient was successfully treated with a first generation therapy, CHOP modified regimen (cyclophosphamide 600 mg/m2 intravenously on d 1, epirubicin 55 mg/m2 intravenously on d 1, vincristine 1.2 mg/m2 intravenously on d 1, prednisone 60 mg/m2 on d 1-5), and a complete response was achieved. The (18)F-fluorodeoxyglucose positron emission tomography was used to assess the therapy outcome. A brief review of literature is provided.
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Affiliation(s)
- Chiara Fulignati
- Department of Internal Medicine, Centre of Experimental and Clinical Oncology, University of Florence, School of Medicine, Viale Morgagni, 85, I-50134 Firenze, Italy
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Di Bella N, Reynolds C, Faragher D, Muscato J, Boehm KA, Asmar L. An open-label pilot study of pentostatin, mitoxantrone, and rituximab in patients with previously untreated, Stage III or IV, low-grade non-Hodgkin lymphoma. Cancer 2005; 103:978-84. [PMID: 15672388 DOI: 10.1002/cncr.20820] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND In a previous study, the authors demonstrated that the combination of pentostatin (P) and rituximab (R) was well tolerated and was active in patients with low-grade non-Hodgkin lymphoma (NHL). In the current study, mitoxantrone (M) was added to P + R to evaluate the toxicity and efficacy of this three-drug combination (PMR). METHODS Twenty-four previously untreated patients with histologically proven, Stage III or IV, low-grade NHL were registered between April and September, 2002. Patients received P (4 mg/m2), M (10 mg/m2), and R (375 mg/m2) every 28 days (M on Day 1; P and R on Days 1 and 8; in Cycle 1, R was given on Day 8 only). Eighty-three percent of patients had Stage IV disease, the median patient age was 62 years (range, 4-81 years), and the performance status was 0-2. RESULTS Responses included 9 patients who achieved complete remission (CR) (38%), 3 patients with unconfirmed CR (CRu) (12%), 8 patients who achieved partial remission (33%), and 4 patients who achieved stable disease (17%); the overall response rate (CR + CRu + PR) was 83%. PMR appeared to result in comparable activity in all histologies. The median response duration was 10.0 months (range, 3.5-15.1 months). Patients received a median of 5 cycles (range, 1-10 cycles). Eighteen patients (75%) required dose reduction or delay due to toxicity, mainly neutropenia (the administration of growth factors was not permitted). Three patients died (two patients died of disease progression, and one patient died from unrelated cardiopulmonary arrest). Grade > or = 3 drug-related toxicities included neutropenia (67%), leukopenia and febrile neutropenia (17% each), and sepsis (8%), and 38% of neutropenic episodes occurred in Cycles 1 and 2. CONCLUSIONS In this study, PMR was active and well-tolerated in patients with low-grade NHL, and the combination is deserving of further study.
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