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1
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Lin H, Zhou K, Peng Z, Liang L, Cao J, Mei J. Surgery and chemotherapy cannot improve the survival of patients with early-stage mucosa-associated lymphoid tissue derived primary pulmonary lymphoma. Front Oncol 2022; 12:965727. [PMID: 36081547 PMCID: PMC9446888 DOI: 10.3389/fonc.2022.965727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/18/2022] [Indexed: 11/13/2022] Open
Abstract
Background To date, there is no treatment consensus on mucosa-associated lymphoid tissue (MALT) derived primary pulmonary lymphoma (PPL). Methods We identified patients with early-stage MALT-type PPL from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program database. The patients were divided into four groups according to treatment modalities: None of surgery or chemotherapy (None) group, Surgery alone group, Chemotherapy alone (Chemo alone) group, and Surgery plus chemotherapy (Surgery + chemo) group. Overall survival (OS) and cancer-specific survival (CSS) were study endpoints. We performed Cox regression analyses, propensity score-matched analyses (PSM) and Kaplan-Meier (KM) survival curves to compare the survival among different groups. Results A total of 953 patients were included in our analysis with 302, 403, 175, and 73 cases in the None, Surgery alone, Chemo alone, and Surgery + chemo groups, respectively. In this cohort, the estimated 3-year, 5-year and 10-year OS rates were 86.95%, 78.91%, and 55.89%, respectively. Meanwhile, the estimated 3-year, 5-year and 10-year CSS rates were 96.71%, 93.73%, and 86.84%, respectively. Multivariate Cox regression analyses demonstrated that increasing age, tumors located in the lower lobe, and stage II were significant predictors of poorer OS while increasing age and tumors located in the bilateral lungs were associated with lower CSS. After PSM analyses, the KM survival curves showed no significant differences in OS or CSS among the four groups. Conclusion Early-stage MALT-type PPL is indolent in nature. Neither surgery, chemotherapy nor a combination of surgery and chemotherapy can improve OS and CSS, suggesting that “watch and wait” may be a reasonable alternative.
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Affiliation(s)
- Huahang Lin
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Ke Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Zhiyu Peng
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Linchuan Liang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Jie Cao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
| | - Jiandong Mei
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
- Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China
- *Correspondence: Jiandong Mei,
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2
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Chung HU, Son JH. Ocular adnexal mucosa-associated lymphoid tissue lymphoma: a narrative review. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2022; 39:3-11. [PMID: 34521183 PMCID: PMC8895963 DOI: 10.12701/yujm.2021.01263] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/01/2021] [Accepted: 08/12/2021] [Indexed: 12/02/2022]
Abstract
Lymphoma is the most common primary tumor of the orbit, accounting for 55% of all orbital malignancies. When divided into histopathological subtypes, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises the largest proportion. Clinical manifestations are unspecific, but in patients with slow-growing painless orbital mass, or red conjunctival lesion suggestive of 'salmon patch', ocular adnexa lymphoma (OAL) should be suspected. Although the pathogenetic mechanism of ocular adnexal MALT lymphoma (OAML) is not yet fully understood, the relationship between OAML and Chlamydia psittaci has been hypothesized recently, similar to that between gastric MALT lymphoma and Helicobacter pylori. This suggests a new treatment option for OAML; bacterial eradication therapy with systemic antibiotics. Several other treatment methods for OAML have been introduced, but no treatment guidelines have been established yet. In this article, we summarize the current knowledge on the clinical features, pathogenesis, diagnostic methods, therapeutic strategies, and prognosis of OAML.
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Affiliation(s)
- Hyun Uk Chung
- Yeungnam Eye Center, Yeungnam University Hospital, Daegu, Korea
| | - Jun Hyuk Son
- Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea
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3
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Ramos CA. Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal). Hematology 2018. [DOI: 10.1016/b978-0-323-35762-3.00079-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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4
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Defrancesco I, Arcaini L. Overview on the management of non-gastric MALT lymphomas. Best Pract Res Clin Haematol 2017; 31:57-64. [PMID: 29452667 DOI: 10.1016/j.beha.2017.11.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 11/08/2017] [Accepted: 11/10/2017] [Indexed: 12/15/2022]
Abstract
Extranodal marginal zone B-cell lymphomas (EMZLs) of the mucosa-associated lymphoid tissue (MALT) are indolent lymphomas which can present at any extranodal site. The most frequent localizations (other than stomach) are ocular adnexa, salivary gland, skin, lung and thyroid. Chronic inflammation and antigenic stimulation are a potential risk for the development of MALT lymphomas. While Helicobacter Pylori (HP) is known to be associated with gastric MALT lymphoma and antibiotic therapy is effective in the setting of HP-positive, other microorganisms (such as Chlamydophila Psittaci, Campylobacter Jejiuni, Borrelia Burgdoferi) have been implicated in the pathogenesis of non-gastric MALT lymphomas. However, antibiotic therapy has not been extensively investigated for the non-gastric type, except for ocular adnexal MALT lymphoma, which could benefit from an upfront treatment with doxycycline. Surgery, radiotherapy, Rituximab alone or in combination with chemotherapy and "chemo-free" approaches, including lenalidomide, have shown efficacy in the treatment of non-gastric MALT lymphomas.
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Affiliation(s)
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
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5
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Long-term results of a phase 2 study of rituximab and bendamustine for mucosa-associated lymphoid tissue lymphoma. Blood 2017; 130:1772-1774. [DOI: 10.1182/blood-2017-07-795302] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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6
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Ma WL, Yao M, Liao SL, Tang JL, Wang YC, Kuo SH, Cheng AL. Chemotherapy alone is an alternative treatment in treating localized primary ocular adnexal lymphomas. Oncotarget 2017; 8:81329-81342. [PMID: 29113392 PMCID: PMC5655287 DOI: 10.18632/oncotarget.18500] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 05/29/2017] [Indexed: 12/25/2022] Open
Abstract
This study investigated the treatment efficacy and long-term adverse effects of various treatment modalities for primary ocular adnexal lymphomas (POALs). We retrospectively reviewed 107 patients who received first-line chemotherapy, radiotherapy, and other treatment modalities from 1990 to 2015. Nighty-three (87%) patients were diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma, with the orbit being the most common site (49 patients, 46%). Among 91 patients with stage I-IIE1 disease, 26 underwent chemotherapy, 34 underwent radiotherapy, and 31 received other treatment modalities. For chemotherapy, radiotherapy, and other treatment modalities, the 5-year event-free survival (EFS) rates were 90.0%, 89.7%, and 85.8% and the 5-year overall survival (OS) rates were 100%, 90.4%, and 87.5%, respectively. Moreover, among 80 patients with stage I-IIE1 MALT lymphoma, the complete remission, 5-year EFS and OS rates were not significantly different between patients receiving chemotherapy and those receiving radiotherapy. Among 16 patients with stage IIE2-IVE disease, the 5-year EFS rates for chemotherapy alone (n = 11) and combined radiotherapy and chemotherapy (n = 5) were 61.7% and 80%, respectively, whereas the 5-year OS rate for both groups was 80.0%. Neutropenia (15.2%) was the most common side effect in patients who received chemotherapy, whereas cataract (16.3%) was the most common late sequela in patients who received radiotherapy. Multivariate analysis revealed that old age (> 60 y) and an advanced stage (stage III/IV) were prognostic factors for poor OS. Our results indicate that chemotherapy yields satisfactory disease control and fewer side effects, and acts as an alternative therapy for patients with localized POALs.
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Affiliation(s)
- Wei-Li Ma
- Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming Yao
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shu-Lang Liao
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jih-Luh Tang
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yao-Ching Wang
- Department of Biomedical Imaging and Radiological Science, College of Health Care, China Medical University, Taichung, Taiwan
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
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7
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Raderer M, Kiesewetter B, Ferreri AJM. Clinicopathologic characteristics and treatment of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). CA Cancer J Clin 2016; 66:153-71. [PMID: 26773441 DOI: 10.3322/caac.21330] [Citation(s) in RCA: 170] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 7% to 8% of newly diagnosed lymphomas. Because of its association with infectious causes, such as Helicobacter pylori (HP) or Chlamydophila psittaci (CP), and autoimmune diseases, it has become the paradigm of an antigen-driven malignancy. MALT lymphoma usually displays an indolent course, and watch-and-wait strategies are justified initially in a certain percentage of patients. In patients with gastric MALT lymphoma or ocular adnexal MALT lymphoma, antibiotic therapy against HP or CP, respectively, is the first-line management of choice, resulting in lymphoma response rates from 75% to 80% after HP eradication and from 33% to 65% after antibiotic therapy for CP. In patients who have localized disease that is refractory to antibiotics, radiation is widely applied in various centers with excellent local control, whereas systemic therapies are increasingly being applied, at least in Europe, because of the potentially systemic nature of the disease. Therefore, the objective of this review is to briefly summarize the clinicopathologic characteristics of this distinct type of lymphoma along with current data on management strategies.
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Affiliation(s)
- Markus Raderer
- Programme Director for Extranodal Lymphomas, Department of Internal Medicine I, Division of Oncology, Medical University Vienna, Vienna, Austria
| | - Barbara Kiesewetter
- Resident-in-Training, Department of Internal Medicine I, Division of Oncology, Medical University Vienna, Vienna, Austria
| | - Andrés J M Ferreri
- Director, Unit of Lymphoid Malignancies, Division of Onco-Hematological Medicine, Department of Onco-Hematology, National Institute for Research and Treatment, San Raffaele Scientific Institute, Milano, Italy
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8
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Borie R, Wislez M, Antoine M, Copie-Bergman C, Thieblemont C, Cadranel J. Pulmonary mucosa-associated lymphoid tissue lymphoma revisited. Eur Respir J 2016; 47:1244-60. [PMID: 26797028 DOI: 10.1183/13993003.01701-2015] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 11/23/2015] [Indexed: 12/22/2022]
Abstract
This general review sought to clarify the pathophysiological, diagnostic, prognostic, and therapeutic features of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.MALT lymphoma is the most common pulmonary B-cell lymphoma, which usually occurs in the context of acquired MALT. The disease is slow-growing with an asymptomatic chronic alveolar opacity visible on radiography. Diagnosis requires tissue samples that should be retrieved using minimally invasive techniques, such as bronchoscopy or computed tomography-guided biopsies. The pathophysiology includes cytogenetic abnormalities and autoimmune diseases, whereas an association with a chronic pulmonary infection is still suspected but not yet demonstrated. Disease prognosis is typically excellent and the current available treatments are discussed in this review, including the decision not to treat, surgery, and single- or double-agent chemotherapy.
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Affiliation(s)
- Raphael Borie
- Service de Pneumologie A, Centre de compétences maladies pulmonaires rares, AP-HP, Hôpital Bichat, Paris, France
| | - Marie Wislez
- Service de Pneumologie, Centre de compétences maladies pulmonaires rares, AP-HP, Hôpital Tenon, Paris, France GRC-THERANOSCAN, Université P&M Curie, Université Paris 6, Paris, France
| | - Martine Antoine
- GRC-THERANOSCAN, Université P&M Curie, Université Paris 6, Paris, France Service d'Anatomie pathologique, AP-HP, Hôpital Tenon, Paris, France
| | | | - Catherine Thieblemont
- Service d'Hémato-oncologie, AP-HP, Hôpital Saint-Louis, Université Diderot, Sorbonne Paris Cité, Paris, France
| | - Jacques Cadranel
- Service de Pneumologie, Centre de compétences maladies pulmonaires rares, AP-HP, Hôpital Tenon, Paris, France GRC-THERANOSCAN, Université P&M Curie, Université Paris 6, Paris, France
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9
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Kiesewetter B, Ferreri AJM, Raderer M. Chemoimmunotherapy for Mucosa-Associated Lymphoid Tissue-Type Lymphoma: A Review of the Literature. Oncologist 2015; 20:915-25. [PMID: 26156327 PMCID: PMC4524756 DOI: 10.1634/theoncologist.2015-0109] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 04/13/2015] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Biological treatments, chemoimmunotherapy, and radiotherapy are associated with excellent disease control in both gastric and extragastric mucosa-associated lymphoid tissue (MALT) lymphomas. Systemic treatment approaches with both oral and i.v. agents are being increasingly studied, not only for patients with disseminated MALT lymphoma, but also for those with localized disease. To date, however, recommendations for the use of available systemic modalities have not been clearly defined. MATERIALS AND METHODS The present report reviews the current data on systemic treatment options for patients with MALT lymphoma and provides recommendations for their use in everyday practice. RESULTS Different chemotherapeutic agents, including anthracyclines, alkylators, and purine analogs, have been successfully tested in patients with MALT lymphoma. Reducing side effects while maintaining efficacy should be the main goal in treating these indolent lymphomas. From the data from the largest trial performed to date, the combination of chlorambucil plus rituximab (R) appears to be active as first-line treatment. Similarly, R-bendamustine also seems to be highly effective, but a longer follow-up period is needed. R-monotherapy results in lower remission rates, but seems a suitable option for less fit patients. New immunotherapeutic agents such as lenalidomide (with or without rituximab) or clarithromycin show solid activity but have not yet been validated in larger collectives. CONCLUSION Patients with MALT lymphoma should be treated within prospective trials to further define optimal therapeutic strategies. Systemic treatment is a reasonable option with potentially curative intent in everyday practice. Based on the efficacy and safety data from available studies, the present review provides recommendations for the use of systemic strategies.
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Affiliation(s)
- Barbara Kiesewetter
- Division of Oncology, Department of Internal Medicine I, Medical University Vienna, Vienna, Austria; Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy
| | - Andrés J M Ferreri
- Division of Oncology, Department of Internal Medicine I, Medical University Vienna, Vienna, Austria; Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy
| | - Markus Raderer
- Division of Oncology, Department of Internal Medicine I, Medical University Vienna, Vienna, Austria; Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy
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10
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Sammassimo S, Pruneri G, Andreola G, Montoro J, Steffanoni S, Nowakowski GS, Gandini S, Negri M, Habermann TM, Raderer M, Li ZM, Zinzani PL, Adam P, Zucca E, Martinelli G. A retrospective international study on primary extranodal marginal zone lymphoma of the lung (BALT lymphoma) on behalf of International Extranodal Lymphoma Study Group (IELSG). Hematol Oncol 2015; 34:177-183. [PMID: 26152851 DOI: 10.1002/hon.2243] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 05/21/2015] [Accepted: 05/31/2015] [Indexed: 11/10/2022]
Abstract
Primary lymphoma of the lung is a rare entity. Clinical features, optimal treatment, role of surgery and outcomes are not well defined, and the follow-up is variable in published data. Clinical data of 205 patients who were confirmed to have bronchus mucosa-associated lymphoid tissue lymphoma from December 1986 to December 2011 in 17 different centres worldwide were evaluated. Fifty-five per cent of the patients were female. The median age at diagnosis was 62 (range 28-88) years. Only 9% had a history of exposure to toxic substances, while about 45% of the patients had a history of smoking. Ten per cent of the patients had autoimmune disease at presentation, and 19% patients had a reported preexisting lung disease. Treatment modalities included surgery alone in 63 patients (30%), radiotherapy in 3 (2%), antibiotics in 1 (1%) and systemic treatment in 128 (62%). Patients receiving a local approach, mainly surgical resection, experienced significantly improved progression-free survival (p = 0.003) versus those receiving a systemic treatment. There were no other significant differences among treatment modalities. The survival data confirm the indolent nature of the disease. Local therapy (surgery or radiotherapy) results in long-term disease-free survival for patients with localized disease. Systemic treatment, including alkylating-containing regimens, can be reserved to patients in relapse after incomplete surgical excision or for patients with advanced disease. Copyright © 2015 John Wiley & Sons, Ltd.
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Affiliation(s)
- Simona Sammassimo
- Haematoncology Division, European Institute of Oncology, Milan, Italy
| | | | - Giovanna Andreola
- Haematoncology Division, European Institute of Oncology, Milan, Italy
| | - Juan Montoro
- Haematoncology Division, European Institute of Oncology, Milan, Italy
| | - Sara Steffanoni
- Haematoncology Division, European Institute of Oncology, Milan, Italy
| | | | - Sara Gandini
- Epidemiology and Biostatistics Department, European Institute of Oncology, Milan, Italy
| | - Mara Negri
- Haematoncology Division, European Institute of Oncology, Milan, Italy
| | | | | | - Zhi-Ming Li
- Sun Yat-Sen University Cancer Center, Guangzhou, China
| | | | - Patrick Adam
- Pathologisches Institut der Universität, Würzburg, Germany
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Abstract
Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) is an indolent lymphoma arising in extranodal sites. Several infectious agents and autoimmune disorders have been implicated in its pathogenesis. The stomach represents the most common and best-studied organ involved by MALT lymphoma and its development is strongly associated with Helicobacter pylori (Hp) infection. MALT lymphomas are characterized by an indolent clinical course and excellent survival in most cases, independently of the treatment delivered. Recent progress in the knowledge of the etiology and the cellular and molecular pathological events related to MALT lymphomas allowed us to improve our clinical understanding of this disease entity and to better define treatment strategies.
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12
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Kiesewetter B, Raderer M. Mucosa-associated lymphoid tissue lymphoma: a perspective on current and future therapeutic strategies. Expert Opin Orphan Drugs 2015. [DOI: 10.1517/21678707.2015.1034270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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13
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Abstract
Marginal zone lymphomas (MZL) represent around 8 % of all non-Hodgkin lymphomas. During the last decades a number of studies have addressed the mechanisms underlying the disease development. Extranodal MZL lymphoma usually arises in mucosal sites where lymphocytes are not normally present from a background of either autoimmune processes, such as Hashimoto thyroiditis or Sjögren syndrome or chronic infectious conditions. In the context of a persistent antigenic stimulation, successive genetic abnormalities can progressively hit a B-cell clone among the reactive B-cells of the chronic inflammatory tissue and give rise to a MALT lymphoma. The best evidence of an etiopathogenetic link is available for the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, a successful eradication of this micro-organism with antibiotics can be followed by gastric MALT lymphoma regression in more than 2/3 of cases. Other microbial agents have been implicated in the pathogenesis of MZL arising in the skin (Borrelia burgdorferi), in the ocular adnexa (Chlamydophila psittaci), and in the small intestine (Campylobacter jejuni). The prevalence of hepatitis C virus (HCV) has also been reported higher in MZL patients (particularly of the splenic type) than in the control population, suggesting a possible causative role of the virus. In non-gastric MALT lymphoma and in splenic MZL the role of the antimicrobial therapy is, however, less clear. This review summarizes the recent advances in Marginal Zone Lymphomas, addressing the critical points in their diagnosis, staging and clinical management.
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14
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Salar A, Domingo-Domenech E, Panizo C, Nicolás C, Bargay J, Muntañola A, Canales M, Bello JL, Sancho JM, Tomás JF, Rodríguez MJ, Peñalver FJ, Grande C, Sánchez-Blanco JJ, Palomera L, Arranz R, Conde E, García M, García JF, Caballero D, Montalbán C. First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial. LANCET HAEMATOLOGY 2014; 1:e104-11. [DOI: 10.1016/s2352-3026(14)00021-0] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 10/27/2014] [Indexed: 12/14/2022]
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15
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Zinzani PL, Pellegrini C, Broccoli A, Gandolfi L, Stefoni V, Casadei B, Maglie R, Argnani L, Pileri S. Fludarabine-Mitoxantrone-Rituximab regimen in untreated indolent non-follicular non-Hodgkin's lymphoma: experience on 143 patients. Hematol Oncol 2014; 33:141-6. [DOI: 10.1002/hon.2151] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 06/04/2014] [Indexed: 11/05/2022]
Affiliation(s)
- Pier Luigi Zinzani
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Cinzia Pellegrini
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Alessandro Broccoli
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Letizia Gandolfi
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Vittorio Stefoni
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Beatrice Casadei
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Roberto Maglie
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Lisa Argnani
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
| | - Stefano Pileri
- Institute of Hematology ‘L. e A. Seràgnoli’; University of Bologna; Bologna Italy
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16
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Conconi A, Raderer M, Franceschetti S, Devizzi L, Ferreri AJM, Magagnoli M, Arcaini L, Zinzani PL, Martinelli G, Vitolo U, Kiesewetter B, Porro E, Stathis A, Gaidano G, Cavalli F, Zucca E. Clinical activity of everolimus in relapsed/refractory marginal zone B-cell lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group. Br J Haematol 2014; 166:69-76. [DOI: 10.1111/bjh.12845] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Accepted: 01/27/2014] [Indexed: 12/29/2022]
Affiliation(s)
- Annarita Conconi
- Division of Haematology; Department of Translational Medicine; Amedeo Avogadro University of Eastern Piedmont; AOU Maggiore della Carità; Novara Italy
- Haematology Unit; Department of Internal Medicine; Ospedale degli Infermi; Biella Italy
| | - Markus Raderer
- Division of Oncology; Department of Internal Medicine I; Medical University of Vienna; Vienna Austria
| | - Silvia Franceschetti
- Division of Haematology; Department of Translational Medicine; Amedeo Avogadro University of Eastern Piedmont; AOU Maggiore della Carità; Novara Italy
| | - Liliana Devizzi
- Medical Oncology; Fondazione IRCCS Istituto Nazionale Tumori; Milan Italy
| | - Andrés J. M. Ferreri
- Unit of Lymphoid Malignancies; Department of Onco-Haematology; San Raffaele Scientific Institute; Milan Italy
| | - Massimo Magagnoli
- Department of Medical Oncology and Haematology; Istituto Clinico Humanitas; Rozzano Milan Italy
| | - Luca Arcaini
- Department of Molecular Medicine; University of Pavia; Pavia Italy
- Department of Haematology Oncology; Fondazione IRCCS Policlinico San Matteo; Pavia Italy
| | - Pier Luigi Zinzani
- Institute of Haematology “L. e A. Seràgnoli”; University of Bologna; Bologna Italy
| | | | - Umberto Vitolo
- Haematology 2; San Giovanni Battista Hospital and University; Torino Italy
| | - Barbara Kiesewetter
- Division of Oncology; Department of Internal Medicine I; Medical University of Vienna; Vienna Austria
| | - Elena Porro
- Lymphoma Unit; IOSI - Oncology Institute of Southern Switzerland; Ospedale San Giovanni; Bellinzona Switzerland
| | - Anastasios Stathis
- Lymphoma Unit; IOSI - Oncology Institute of Southern Switzerland; Ospedale San Giovanni; Bellinzona Switzerland
| | - Gianluca Gaidano
- Division of Haematology; Department of Translational Medicine; Amedeo Avogadro University of Eastern Piedmont; AOU Maggiore della Carità; Novara Italy
| | - Franco Cavalli
- Lymphoma Unit; IOSI - Oncology Institute of Southern Switzerland; Ospedale San Giovanni; Bellinzona Switzerland
| | - Emanuele Zucca
- Lymphoma Unit; IOSI - Oncology Institute of Southern Switzerland; Ospedale San Giovanni; Bellinzona Switzerland
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17
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Vanazzi A, Grana C, Crosta C, Pruneri G, Rizzo S, Radice D, Pinto A, Calabrese L, Paganelli G, Martinelli G. Efficacy of ⁹⁰Yttrium-ibritumomab tiuxetan in relapsed/refractory extranodal marginal-zone lymphoma. Hematol Oncol 2013; 32:10-5. [PMID: 23696416 DOI: 10.1002/hon.2078] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 04/12/2013] [Accepted: 04/15/2013] [Indexed: 11/07/2022]
Abstract
We evaluated clinical activity of ⁹⁰Yttrium-ibritumomab (⁹⁰Y-ibritumomab) tiuxetan in extranodal marginal-zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal-zone lymphoma--arisen at any extranodal site--received ⁹⁰Y-ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. ⁹⁰Y-ibritumomab tiuxetan seems to be active in patients with extranodal marginal-zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients.
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Affiliation(s)
- Anna Vanazzi
- Hematoncology Division, European Institute of Oncology, Milan, Italy
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18
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Helicobacter pylori infection, chronic inflammation, and genomic transformations in gastric MALT lymphoma. Mediators Inflamm 2013; 2013:523170. [PMID: 23606792 PMCID: PMC3625579 DOI: 10.1155/2013/523170] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2013] [Accepted: 02/11/2013] [Indexed: 12/13/2022] Open
Abstract
Nowadays, it is believed that the main role in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma plays Helicobacter pylori infection. This world-wide distributed bacteria is in charge of most cases of not only upper gastrointestinal tract disorders but also some of extragastric problems. Constant stimulation of the immune system causes a B-lymphocytes proliferation, which is considered to be responsible for the neoplastic transformation. On the other hand, there are 10%–20% of patients who do not respond to Helicobacter pylori eradication treatment. This group has often a chromosome translocation, which suggests that there is another unknown, so far, pathogenetic mechanism of MALT lymphoma. Majority of genetic abnormalities are connected with nuclear factor-κB (NF-κB) pathway, which activates the uncontrolled proliferation of neoplastic cells. Translocations already described in studies are t(11;18)(q21;q21), which is the most common, t(14;18)(q32;q21), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). This non-Hodgkin's lymphoma is an indolent type originated outside lymph nodes. In more than 50% of cases, it occurs in the stomach. Occasionally, it can be found in salivary and thyroid gland, lung, breast, bladder, skin, or any other place in the human body. This paper is a review of the current knowledge on etiology, pathogenesis, treatment, and follow-up of gastric MALT lymphoma.
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19
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Abstract
Abstract
Indolent B-cell lymphomas that are supposed to derive from the marginal zone (marginal zone lymphomas [MZLs]) include 3 specific entities: extranodal marginal zone lymphoma (EMZL) or mucosa-associated lymphatic tissue (MALT) lymphoma, splenic MZL (SMZL), and nodal MZL (NMZL). The clinical and molecular characteristics are different for each entity, with some shared phenotypic and genetic features. EMZL is the most common entity, accounting for approximately 70% of all MZLs. These neoplasms can arise at virtually any extranodal site and are commonly associated with chronic antigenic stimulation either as a result of infection (eg, Helicobacter pylori in the stomach) or autoimmune disease (eg, Sjögren syndrome and salivary glands). Several chromosomal translocations were also identified in EMZL, accounting in the aggregate for approximately one-third of all cases. SMZL accounts for approximately 20% of all MZLs. Patients typically present with an enlarged spleen and involvement of abdominal lymph nodes and BM. Approximately 40%-50% of SMZLs are associated with deletions of chromosome 7q. NMZL is the less common entity, representing approximately 10% of all MZLs. Patients with NMZL, by definition, have lymph node–based disease without involvement of the spleen or extranodal sites. The molecular pathogenesis of NMZL is still unknown.
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20
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Lévy M, Copie-Bergman C, Amiot A, Dupuis J, Baleur YL, Belhadj K, Hémery F, Sobhani I, Delfau-Larue MH, Leroy K, Haioun C, Delchier JC. Rituximab and chlorambucil versus rituximab alone in gastric mucosa-associated lymphoid tissue lymphoma according to t(11;18) status: a monocentric non-randomized observational study. Leuk Lymphoma 2012; 54:940-4. [DOI: 10.3109/10428194.2012.729832] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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21
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Joshi M, Sheikh H, Abbi K, Long S, Sharma K, Tulchinsky M, Epner E. Marginal zone lymphoma: old, new, targeted, and epigenetic therapies. Ther Adv Hematol 2012; 3:275-90. [PMID: 23616915 PMCID: PMC3627321 DOI: 10.1177/2040620712453595] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Marginal zone lymphoma (MZL) is an indolent B-cell lymphoma arising from marginal zone B-cells present in lymph nodes and extranodal tissues. MZL comprises 5-17% of all non-Hodgkin's lymphomas in adults. The World Health Organization categorizes MZL into three distinct types based on their site of impact: (1) splenic marginal zone lymphoma (SMZL); (2) nodal marginal zone lymphoma (NMZL); (3) extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, which can be subdivided into gastric and nongastric. The subgroups of MZL share some common features but are different in their biology and behavior. Owing to the rarity of MZL there are few randomized trials available comparing various treatment options and therefore treatment is controversial, lacking standard guidelines. Treatment should be patient tailored and can range from a 'watchful waiting' approach for asymptomatic patients without cytopenias to surgery or localized radiation therapy. Rituximab in combination with chemotherapy has resulted in longer failure-free survival than chemotherapy alone in patients with SMZL. Helicobacter pylori positive gastric MALT shows a good response rate to triple antibiotic therapy. Newer therapies such as bendamustine, everolimus, lenalidomide, vorinostat and phosphoinositide 3-kinase inhibitors are in clinical trials for patients with relapsed or refractory MZL and have shown promising results. We are presently conducting clinical trials testing the efficacy of the epigenetic activity of cladribine as a hypomethylating agent in combination with the histone deacetylase inhibitor (HDACi) vorinostat and rituximab in patients with MZL. Further studies with the newer agents should be done both in newly diagnosed or relapsed/refractory MZL to streamline the care and to avoid the use of toxic chemotherapies as initial treatment.
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Affiliation(s)
- Monika Joshi
- The Hematology-Oncology and Biostatistics Divisions of the Penn State Milton S Hershey Medical Center, Hershey, PA, USA
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22
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de Boer JP, Raderer M, van Tinteren H, Aleman BMP, Boot H, de Jong D. Treatment of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with fludarabine: effect on tumor microenvironment. Leuk Lymphoma 2011; 52:2262-9. [PMID: 21848361 DOI: 10.3109/10428194.2011.607527] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Gastric Helicobacter pylori (HP) positive extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) develops during chronic antigenic stimulation with specific T-cell help. Chemotherapy that acts both on the malignant B-cells and on T-cells in the microenvironment, i.e. nucleoside analogs, might therefore be an attractive treatment. In 14 patients with gastric MALT lymphoma treated with fludarabine, alterations in T-cell subsets were studied in subsequent peripheral blood samples and in gastric biopsies. Treatment with fludarabine resulted in a steep decrease in T-cell subsets in peripheral blood samples. By contrast no decrease in T-cell populations was observed in subsequent gastric biopsy samples and a moderate increase was observed in relative infiltration with CD3 +, CD4 + and CD8 + cells. In addition an increase in density of FOXP3 + cells (i.e. Tregs) was seen (p = 0.047). These alterations in different T-cell subsets were not observed in gastric biopsy samples of patients treated with HP-eradication only.
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Affiliation(s)
- Jan-Paul de Boer
- Department of Medical Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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23
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Phase II trial of rituximab plus CVP combination chemotherapy for advanced stage marginal zone lymphoma as a first-line therapy: Consortium for Improving Survival of Lymphoma (CISL) study. Ann Hematol 2011; 91:543-51. [PMID: 21922208 DOI: 10.1007/s00277-011-1337-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2011] [Accepted: 09/01/2011] [Indexed: 12/14/2022]
Abstract
We conducted a multicenter, phase II trial to investigate the efficacy and safety of rituximab plus CVP (R-CVP) combination therapy for patients with previously untreated stage III or IV marginal zone lymphoma (MZL). The treatment consisted of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2) and vincristine 1.4 mg/m(2) (maximum 2.0 mg) being given intravenously on day 1 and oral prednisolone 100 mg on days 1-5. The treatment was repeated every 3 weeks and this was continued for six or eight cycles. Forty-two patients were enrolled from 13 institutes in Korea. Among them, two patients were dropped after the first and second cycles of chemotherapy, respectively, without evaluation. The 40 patients received a total of 287 cycles of R-CVP chemotherapy. The overall response rate was 88% (95% CI, 77-98%) with 24 complete responses (60%). The median duration of response was 28.3 months. After a median follow-up of 38.2 months, the estimated 3-year progression-free survival and overall survival were 59% and 95%, respectively. There were 30/287 cycles (11%) and 5/287 cycles (2%) of grade 3 or 4 neutropenia and febrile neutropenia, respectively. The R-CVP regimen can be an effective and tolerable first-line immunochemotherapy regimen for advanced stage MZL.
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24
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Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJM, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E. Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol 2010; 22:689-695. [PMID: 20810546 DOI: 10.1093/annonc/mdq416] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy. PATIENTS AND METHODS Thirty-two patients with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m(2) i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles. RESULTS Median age was 63 years (range, 37-82 years). Median number of prior therapies was 2 (range, 1-4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression. CONCLUSION Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.
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Affiliation(s)
- A Conconi
- Department of Clinical and Experimental Medicine, Division of Hematology, AOU Maggiore della Carità, Amedeo Avogadro University of Eastern Piedmont, Novara.
| | - G Martinelli
- Division of Hematology-Oncology, European Institute of Oncology, Milan, Italy
| | | | - P L Zinzani
- Institute of Hematology and Medical Oncology 'L. e A. Seràgnoli', University of Bologna, Bologna
| | - A J M Ferreri
- Unit of Lymphoid Malignancies, Medical Oncology Unit, Department of Oncology, San Raffaele H Scientific Institute, Milan
| | - L Rigacci
- Department of Hematology, Careggi Hospital and University of Florence, Florence
| | - L Devizzi
- Cristina Gandini Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan
| | - U Vitolo
- SC Ematologia II, Azienda Ospedaliera e Universitaria San Giovanni Battista, Turin
| | - S Luminari
- Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy
| | - F Cavalli
- IOSI-Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - E Zucca
- IOSI-Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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25
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Lévy M, Copie-Bergman C, Molinier-Frenkel V, Riou A, Haioun C, Gaulard P, Delfau-Larue MH, Sobhani I, Leroy K, Delchier JC. Treatment of t(11;18)-positive gastric mucosa-associated lymphoid tissue lymphoma with rituximab and chlorambucil: clinical, histological, and molecular follow-up. Leuk Lymphoma 2009; 51:284-90. [DOI: 10.3109/10428190903431820] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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26
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Oh SY, Kim WS, Kim SJ, Kim JS, Kim SH, Lee DH, Won JH, Hwang IG, Kim MK, Lee SI, Kim JG, Yang DH, Kang HJ, Choi CW, Park J, Choi YJ, Kim HJ, Kwon JH, Suh C, Kim HJ. Relapsed or refractory nongastric marginal zone B-cell lymphoma: multicenter retrospective analysis of 92 cases. Am J Hematol 2009; 84:826-9. [PMID: 19890833 DOI: 10.1002/ajh.21557] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Over its long survival duration, marginal zone B-cell lymphoma (MZL) routinely involves frequent relapses. In this study, we conducted a retrospective analysis to identify the clinical features and outcomes of relapsed or refractory MZL. From 1995 to 2008, a total of 92 patients with relapsed MZL were retrospectively analyzed. The median age of our subjects was 53.5 years (range: 23-82 years). The most common primary sites of involvement were the orbit and ocular adnexa (28.3%) followed by the lymph node and lymphatic organs (23.9%), and multiple mucosa-associated lymphoid tissue (MALT) sites (13.0%). The median time to relapse from initial diagnosis was 25.5 months. Of the 53 patients with Stage I or II at diagnosis, 42 patients (79.2%) evidenced locoregional recurrence. Among these locoregional relapsed patients, 27 patients achieved CR (54.1%) or PR (18.9%). In addition to the 39 patients initially in advanced Stage III or IV, a total of 50 patients were in advanced stage at relapse. Among those patients with advanced stage at relapse, 44 patients were treated. The overall response rate was 54.5% (24 patients), with 18 CRs and 6 PRs. The median time to progression (TTP) was 34.1 months (95% CI: 11.3-56.9 months) and the estimated 5-year overall survival (OS) was 84.3%. The majority of them was controlled well with salvage treatment, and could achieve prolonged survival. However, patients' refractory to initial therapy and advanced relapse evidenced shorter TTP and OS. Thus, we need to consider more aggressive treatment in cases of refractory MZL or advanced relapsed MZL.
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Affiliation(s)
- Sung Yong Oh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea
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27
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Ferreri AJM, Dolcetti R, Magnino S, Doglioni C, Ponzoni M. Chlamydial infection: the link with ocular adnexal lymphomas. Nat Rev Clin Oncol 2009; 6:658-69. [PMID: 19806147 DOI: 10.1038/nrclinonc.2009.147] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chlamydiae are obligate intracellular bacteria that grow in eukaryotic cells and cause a wide spectrum of diseases. They can establish persistent infections, are mitogenic in vitro, promote polyclonal cell proliferation in vivo and induce resistance to apoptosis in infected cells-properties that might contribute to tumorigenesis. In fact, Chlamydophila psittaci (Cp) has been linked to the development and maintenance of ocular adnexal marginal zone B-cell lymphoma (OAMZL). In this indolent malignancy, Cp is transported by monocytes and macrophages and causes both local and systemic infection. Cp elementary bodies are viable and infectious in the conjunctiva and peripheral blood of patients with OAMZL. Bacterial eradication with antibiotic therapy is often followed by lymphoma regression. Despite recent advances in the understanding of this bacterium-lymphoma association, several questions remain unanswered. For instance, prevalence variations among different geographical areas and related diagnostic and therapeutic implications remain a major investigational issue. We will focus on clinical and therapeutic implications of chlamydial infections in patients with lymphomas and summarize the current knowledge on the association between Cp infection and OAMZL. Available data on the epidemiology, biology and pathogenesis of this association are analyzed and new investigative and clinical approaches are discussed.
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Affiliation(s)
- Andrés J M Ferreri
- Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy.
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28
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Oh SY, Kim WS, Lee DH, Kim SJ, Kim SH, Ryoo BY, Kang HJ, Choi YJ, Chung JS, Kim HJ, Suh C. Phase II study of gemcitabine for treatment of patients with advanced stage marginal zone B-cell lymphoma: Consortium for Improving Survival of Lymphoma (CISL) trial. Invest New Drugs 2009; 28:171-7. [PMID: 19421710 DOI: 10.1007/s10637-009-9260-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2009] [Accepted: 04/17/2009] [Indexed: 01/11/2023]
Abstract
BACKGROUND Therapeutic approaches to marginal zone B-cell lymphoma (MZL) continue to evolve. Localized MZL responds favorably to local treatments, including surgery and/or local radiation therapy. However, MZL manifests as a disseminated disease in one-third of the cases at diagnosis. Moreover, relapses involving distant sites after local therapy have been reported previously. Therefore, the search for effective forms of systemic therapy is a critical issue. We conducted this multi-center, phase II trial to assess the efficacy and safety of gemcitabine single chemotherapy for patients with stage III/IV MZL. METHODS Patients received gemcitabine 1250 mg/m(2) on days 1 and 8 of each cycle. The treatment was repeated every 3 weeks and continued for 6 cycles until disease progression, withdrawal due to toxicity, or withdrawal of consent. RESULTS Between Sep. 2006 and Sep. 2008, a total of 16 patients were enrolled (with informed consent) into this trial from 6 institutes in Korea. Among these patients, 4 patients dropped out without evaluation. The median age of the 12 (9 males, 3 females) evaluated patients was 62 (range 25-73) years. Seven patients (58%) evidenced involvement of extranodal sites. All patients received previous treatment for MZL. The patients received a total of 69 cycles of gemcitabine chemotherapy (range 3-6 [median 6] cycles/person). There were 2 PR (17%; 95% Confidence Interval [CI], 0.0-41%), 9 SD (75%), and 1 PD (8%). There were 8/69 cycles (12%) of grade 3/4 neutropenia. Non-hematologic toxicities were mild and tolerable. There were 5 cycles (8%) of delayed chemotherapy (median 1 week) owing to neutropenia. Dose reduction was required in 12 cycles. However, no treatment-related death occurred in this study. The median TTP was 10.2 months (95% CI, 5.3-15.1). As the response rate in stage I did not justify progressing to stage II (> or = 8/15), this study had to be discontinued, in accordance with the established protocols. CONCLUSION Gemcitabine as a single agent, in this dosage and at this schedule, evidenced minimal clinical activity in cases of advanced MZL.
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Affiliation(s)
- Sung Yong Oh
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea
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Orciuolo E, Buda G, Sordi E, Baraté C, Galimberti S, Ciancia E, Petrini M. 2CdA chemotherapy and rituximab in the treatment of marginal zone lymphoma. Leuk Res 2009; 34:184-9. [PMID: 19414190 DOI: 10.1016/j.leukres.2009.04.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2009] [Revised: 04/04/2009] [Accepted: 04/04/2009] [Indexed: 02/07/2023]
Abstract
Standard chemotherapic approach for MZL is missing. We are presenting our monocenter experience with 2CdA+/-rituximab. Patients received 2CdA, 5mg/m(2), weekly, for 6 weeks. Patients receiving rituximab underwent to antibody administration in association with 2CdA, or after the end of chemotherapy. Global ORR was 89.3%, with 53.6% CR, with 60 months of median of TTF. 2CdA and rituximab led to 96.5% ORR, with 60.3% CR, while 2CdA alone to 73.1% ORR, with 38.5% CR. TTF median was reached at 35 months with 2CdA alone; not reached yet in the combination arm. Considering subgroups of MZL, combination therapy has a more favorable outcome in SMZL and NMZL, while MALT does not differ. However, all subgroups present a delayed relapse. Considering minimal residual disease (MRD), adding of rituximab converted 65.0% to negativity versus 15.4% of 2CdA alone, with TTF in positive patients reached after 34 months; not reached yet in negatives. Concomitant use of rituximab with 2CdA allowed an ORR of 98.0%, with 68% CR and 56.3% of MRD conversion, while consequent use 100%, 54.6%, and 70.8%, respectively. TTF does not differ. 2CdA therapy is effective in the treatment of MZL. Adding rituximab allows increasing ORR and CR, prolonging TTF.
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Affiliation(s)
- Enrico Orciuolo
- Department of Oncology, Transplants and Advanced Technologies, Haematology Section, University of Pisa, Ospedale S. Chiara, Via Roma 56, 56126 Pisa, Italy.
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Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica 2009; 94:738-42. [PMID: 19336742 DOI: 10.3324/haematol.2008.001537] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
We have performed a phase II study to evaluate bortezomib in patients with MALT-lymphoma. Sixteen patients entered the trial, 4 had gastric MALT-lymphoma, 7 of the ocular adnexa, one of the colon, and 2 of the parotid, and one patient each the lung and the breast. Bortezomib was given at 1.5 mg/m(2) days 1, 4, 8 and 11; repeated every 21 days. The overall response rate was 80% (13/16); 7 patients achieved complete remission (43%), 6 partial response (37%) and 3 stable disease. After a median follow-up of 23 months (range; 8-26), all patients are alive and 4 have relapsed. Fifteen patients required dose reductions due to either neuropathy (7 patients) or diarrhea (8 patients). Bortezomib appears to be active in patients with MALT-lymphoma. However, an unexpectedly high rate of toxicities was seen, warranting assessment of combination schedules with bortezomib at a lower dose than given in our study.
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Affiliation(s)
- Marlene Troch
- Department of Internal Medicine I, Division of Oncology, Medical University Vienna, Waehringer Guertel 18-20, Vienna, Austria
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Robak T, Korycka A, Lech-Maranda E, Robak P. Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules 2009; 14:1183-226. [PMID: 19325518 PMCID: PMC6253893 DOI: 10.3390/molecules14031183] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2009] [Revised: 02/27/2009] [Accepted: 03/10/2009] [Indexed: 01/29/2023] Open
Abstract
For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs) plays an important role. Three of them: pentostatin (DCF), cladribine (2-CdA) and fludarabine (FA) were approved by Food and Drug Administration (FDA) for the treatment of hematological malignancies. Recently three novel PNAs: clofarabine (CAFdA), nelarabine (ara-G) and forodesine (immucillin H, BCX-1777) have been synthesized and introduced into preclinical studies and clinical trials. These agents seem to be useful mainly for the treatment of human T-cell proliferative disorders and they are currently undergoing clinical trials in lymphoid malignancies. However, there are also several studies suggesting the role of these drugs in B-cell malignancies. This review will summarize current knowledge concerning the mechanism of action, pharmacologic properties, clinical activity and toxicity of PNAs accepted for use in clinical practice, as well as new agents available for clinical trials.
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Affiliation(s)
- Tadeusz Robak
- Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, 93-510 Lodz, Ciolkowskiego 2 Str., Poland.
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Voulgarelis M, Moutsopoulos HM. Mucosa-associated lymphoid tissue lymphoma in Sjögren's syndrome: risks, management, and prognosis. Rheum Dis Clin North Am 2009; 34:921-33, viii. [PMID: 18984412 DOI: 10.1016/j.rdc.2008.08.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Sjögren's syndrome is a chronic inflammatory disease primarily affecting the exocrine glands. Its association with lymphoma is well documented, with salivary extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type being the most common and constituting a major disease complication. These neoplasms are antigen-stimulated B-cell lymphomas characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. This article presents a review of the literature and discusses the clinical, histopathologic, therapeutic, and prognostic aspects of these tumors in Sjögren's syndrome. In addition, it highlights the predictor markers of lymphoma development.
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Affiliation(s)
- Michael Voulgarelis
- Department of Pathophysiology, Medical School, National University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece.
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Tomita N, Kodaira T, Tachibana H, Nakamura T, Mizoguchi N, Takada A. Favorable outcomes of radiotherapy for early-stage mucosa-associated lymphoid tissue lymphoma. Radiother Oncol 2009; 90:231-5. [PMID: 19135751 DOI: 10.1016/j.radonc.2008.12.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2008] [Revised: 11/28/2008] [Accepted: 12/08/2008] [Indexed: 12/14/2022]
Abstract
PURPOSE The aim of this study was to evaluate the efficacy of radiation therapy (RT) for early-stage mucosa-associated lymphoid tissue (MALT) lymphoma. MATERIALS AND METHODS Patients with stage IotaE (n=48) and stage capital PE, CyrillicE (n=2) MALT lymphoma treated with RT were reviewed. The primary tumor originated in the stomach in 20 patients, in the orbit in 9 patients, in the conjunctiva or eyelid and the parotid glands in 6 patients each, and 9 patients in the others. The median total RT dose was 32Gy (range, 25.6-50Gy). The median follow-up time was 50 months. RESULTS Although disease did not recur in the RT field in any patient regardless of the total dose, disease recurred outside the RT field in the seven patients. As all recurrences were localized, salvage RT was performed for each recurrence and achieved complete response without recurrence in the field. The 5-year overall survival, local control, and progression-free survival rates were 96.6%, 100%, and 82.2%, respectively. CONCLUSIONS A total dose of 25-30Gy is appropriate for local control of MALT lymphoma. RT is also an effective salvage therapy in cases of localized recurrence.
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Affiliation(s)
- Natsuo Tomita
- Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
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Nakamura T, Ito T, Abe Y, Izutsu K, Gibo J, Itaba S, Kawabe K, Oono T, Igarashi H, Yamaguchi K, Ohshima K, Takayanagi R. Primary pancreatic low-grade mucosa-associated lymphoid tissue lymphoma presenting with multiple masses. Clin J Gastroenterol 2008; 1:168-173. [PMID: 26193698 DOI: 10.1007/s12328-008-0028-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2008] [Accepted: 08/04/2008] [Indexed: 12/13/2022]
Abstract
The case concerns a 55-year-old Japanese man with multiple pancreatic tumors that were incidentally detected by ultrasonography (US) in a routine medical examination. He consulted a doctor since either neuroendocrine tumors or metastases of small-cell lung carcinoma were suspected, because he had an abnormal shadow in the lung. Then he was transferred to our hospital. Imaging studies showed multiple pancreatic tumors of 3.0-cm diameter in the head, 1.0 cm in the body and 1.5 cm in the tail, respectively. Specimen by endoscopic ultrasonography fine-needle aspiration cytology (EUS-FNAC) revealed numerous B-cell lymphocytes, but a definite diagnosis of malignant lymphoma could not be obtained. Therefore, a segmental pancreatic body resection was performed to clarify the features of the tumor for appropriate therapy. Consequently, the final diagnosis was obtained as a low-grade B-cell lymphoma having a lymphoepithelial lesion, which indicated mucosa-associated lymphoid tissue (MALT) lymphoma. Radiation therapy with 31 Gy successfully resulted in complete remission. We report here for the first time on primary pancreatic low-grade MALT lymphoma presenting with multiple pancreatic masses.
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Affiliation(s)
- Taichi Nakamura
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tetsuhide Ito
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Yasunobu Abe
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kensaku Izutsu
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Junya Gibo
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Souichi Itaba
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Ken Kawabe
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Takamasa Oono
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hisato Igarashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Koji Yamaguchi
- Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kouichi Ohshima
- Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kurume University, Fukuoka, Japan
| | - Ryoichi Takayanagi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Stefanovic A, Morgensztern D, Fong T, Lossos IS. Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database. Leuk Lymphoma 2008; 49:1311-20. [PMID: 18604720 DOI: 10.1080/10428190802064933] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Pulmonary marginal zone lymphoma is a rare disease arising from bronchial-associated lymphoid tissue (BALT). There is limited information on clinical presentation, natural history and treatment of this type of lymphoma. We conducted a retrospective review of patients with biopsy-proven BALT lymphoma treated at our institution and patients from the surveillance epidemiology and end results (SEER) database. Twenty-one patients (median age 57) with disease stage IE (n = 10) and IV (n = 11), were treated at our institution. Initial management included observation (n = 4), surgery (n = 5), combination chemotherapy (n = 7), single-agent rituximab (n = 3) and radioimmunotherapy (n = 2). Complete remission was observed in 10, partial remission in 3, stable disease in 7, and disease progression in 1 patient. With a median follow-up of 20 months, Kaplan-Meier estimates for progression-free and overall survival (OS) at 80 months were 90% and 95%, respectively. We identified 326 patients (59% females and 41% males; median age 68 [30 to 85) with BALT lymphoma in the SEER database. Fifty-five per cent had stage IE, 10% stage IIE, 3% stage IIIE, and 22% stage IV disease. After a median follow-up of 35 months, median OS was 112 months, and disease-specific median survival was not reached. At 90 months, disease-specific survival was 85% (CI 77-92) with no significant differences in outcome between patients presenting with different stages. Our single institution experience and review of the SEER database, confirm the indolent features and favourable outcome of this rare disease.
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Affiliation(s)
- Alexandra Stefanovic
- Department of Medicine, Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
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Zucca E, Bertoni F, Stathis A, Cavalli F. Marginal Zone Lymphomas. Hematol Oncol Clin North Am 2008; 22:883-901, viii. [DOI: 10.1016/j.hoc.2008.07.011] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Delchier JC, Lévy M. Prise en charge clinique et thérapeutique du lymphome gastrique du MALT. ONCOLOGIE 2008. [DOI: 10.1007/s10269-008-0911-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Yamashita H, Nakagawa K, Asari T, Murakami N, Igaki H, Ohtomo K. Radiotherapy for 41 patients with stages I and II MALT lymphoma: a retrospective study. Radiother Oncol 2008; 87:412-7. [PMID: 18423914 DOI: 10.1016/j.radonc.2008.03.012] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2008] [Revised: 03/14/2008] [Accepted: 03/14/2008] [Indexed: 12/14/2022]
Abstract
PURPOSE Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following radiation therapy (RT) alone. PATIENTS AND METHODS Forty-one patients with Stages I (37) and II (4) disease were treated between 2000 and 2006. Patients with transformed MALT were excluded. The median age was 60 years (range, 25-86 years), male: female ratio 1:1. Presenting sites included stomach, 11; orbital adnexa, 21; thyroid, 1; other head and neck, 3; small bowel, 3; skin, 1; and rectum, 1. Thirty-five patients (85%) received RT-alone and 6 (15%) received antibiotics followed by RT. RT dose was 30Gy in 20 fractions (fr) in all 41 patients. Mean follow-up time was 32.0 months (range, 2.1-162 months). RESULTS A first complete response was achieved in all 41 patients. Only one patient died from bile duct carcinoma at 22 months from the start of irradiation for conjunctiva MALT lymphoma without recurrence of lymphoma. The other 40 patients were alive. Thirty-eight patients out of them were alive without recurrence. One patient with a duodenal lymphoma had a recurrence in non-irradiated distant sites at 1 month. Another patient with a bilateral eye lid lymphoma had a recurrence within radiation field at 41 months. The absolute local control rate with radiation was 98% (40/41 patients). CONCLUSION Localized MALT lymphomas have excellent prognosis following moderate-dose RT (30Gy/20fr).
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Affiliation(s)
- Hideomi Yamashita
- Department of Radiology, University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo, Japan
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Ferreri AJM, Dolcetti R, Du MQ, Doglioni C, Resti AG, Politi LS, De Conciliis C, Radford J, Bertoni F, Zucca E, Cavalli F, Ponzoni M. Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy. Ann Oncol 2007; 19:835-46. [PMID: 17986622 DOI: 10.1093/annonc/mdm513] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Non-Hodgkin's lymphomas constitute one half of malignancies arising in the orbit and the ocular adnexae. Mucosa-associated lymphoid tissue (MALT)-type lymphoma is the most common histological category in this anatomic region. The incidence of ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) is increasing and recent studies offered new relevant insights in molecular, pathogenetic and therapeutic issues on these neoplasms. A pathogenetic model of antigen-driven lymphoproliferation similar to that reported for Helicobacter pylori-related gastric MALT lymphomas has been hypothesized for OAML. This notion is supported by the association between OAML and Chlamydophila psittaci infection, an association that is of likely pathogenetic relevance and may influence both the biological behavior and the therapeutic management of these neoplasms. However, this association displays evident geographical variability indicating that other etiopathogenic agents could be involved. These recent acquisitions coupled with the occurrence of chromosomal translocations and other genetic alterations, as well as additional risk factors like autoimmune disorders have contributed to render OAML an exciting challenge for a broad group of physicians and scientists. OAML is an indolent and rarely lethal malignancy that, in selected patients, can be managed with observation alone. Lymphomatous lesions are frequently responsible for symptoms affecting patient's quality of life, requiring, therefore, immediate treatment. Several therapeutic strategies are available, often associated with relevant side-effects. However, the therapeutic choice in OAML is not supported by consolidated evidence due to the lack of prospective trials. In this review, we analyze the most relevant biological, molecular, pathological and clinical features of OAML and propose some therapeutic guidelines for patients affected by this malignancy.
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Affiliation(s)
- A J M Ferreri
- Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
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Ferreri AJM, Assanelli A, Crocchiolo R, Dognini GP, Giordano Resti A, Politi LS, Doglioni C, Caligaris Cappio F, Dolcetti R, Ponzoni M. Therapeutic management of ocular adnexal MALT lymphoma. Expert Opin Pharmacother 2007; 8:1073-83. [DOI: 10.1517/14656566.8.8.1073] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Ferreri AJM, Zucca E. Marginal-zone lymphoma. Crit Rev Oncol Hematol 2007; 63:245-56. [PMID: 17583528 DOI: 10.1016/j.critrevonc.2007.04.009] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2006] [Accepted: 04/11/2007] [Indexed: 02/07/2023] Open
Abstract
The term marginal-zone lymphoma (MZL) encompasses three closely related lymphoma subtypes, namely the "low-grade B-cell lymphoma of MALT type" currently named MALT lymphoma, the "nodal marginal-zone B-cell lymphoma" and a provisional entity in the REAL classification named "primary splenic MZL with or without villous lymphocytes". These entities display different characteristics, with evident clinical and biological variations according to the organ where the lymphoma arises. Marginal-zone B-cells are functionally heterogeneous and may differ with respect to the pattern of somatic hypermutation in their Ig variable genes. Sequence and mutation analysis of the rearranged Ig heavy chain variable genes and that somatic mutations pattern indicate that MZL may arise from different subsets of marginal-zone B-cells. Pathogenesis of these groups of lymphomas is correlated to chronic infections, like Helicobacter pylori, hepatitis C virus, Campylobacter jejuni, Chlamydia psittaci and Borrelia burgdorferi. Several therapeutic strategies against these malignancies exist. Surgical resection, radiotherapy and alkylating agent-based chemotherapy constitute standard approaches, while antimicrobial therapies, anti-CD20 therapy and new forms of immunotherapy constitute interesting experimental approaches. However, prospective trials on these malignancies are rare and universally accepted therapeutic guidelines do not exist. MZLs constitute an exciting investigational setting both from molecular and clinical points of view.
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Affiliation(s)
- Andrés J M Ferreri
- Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
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42
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Morgner A, Schmelz R, Thiede C, Stolte M, Miehlke S. Therapy of gastric mucosa associated lymphoid tissue lymphoma. World J Gastroenterol 2007; 13:3554-66. [PMID: 17659705 PMCID: PMC4146794 DOI: 10.3748/wjg.v13.i26.3554] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2007] [Revised: 04/03/2007] [Accepted: 04/26/2007] [Indexed: 02/06/2023] Open
Abstract
Gastric mucosa associated lymphoid tissue (MALT) lymphoma has recently been incorporated into the World Health Organization (WHO) lymphoma classification, termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been clearly shown to play a causative role in lymphomagenesis. Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas, especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma. Hence, the role of eradication therapy, surgery, chemotherapy and radiotherapy is critically analyzed. Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success.
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Affiliation(s)
- Andrea Morgner
- Medical Department I, University Hospital, Technical University Dresden, Germany.
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Isobe K, Kagami Y, Higuchi K, Kodaira T, Hasegawa M, Shikama N, Nakazawa M, Fukuda I, Nihei K, Ito K, Teshima T, Matsuno Y, Oguchi M. A multicenter phase II study of local radiation therapy for stage IEA mucosa-associated lymphoid tissue lymphomas: a preliminary report from the Japan Radiation Oncology Group (JAROG). Int J Radiat Oncol Biol Phys 2007; 69:1181-6. [PMID: 17601683 DOI: 10.1016/j.ijrobp.2007.04.029] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2007] [Revised: 04/17/2007] [Accepted: 04/18/2007] [Indexed: 11/22/2022]
Abstract
PURPOSE The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. METHODS AND MATERIALS The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. RESULTS Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. CONCLUSIONS This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.
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Affiliation(s)
- Koichi Isobe
- Department of Radiology, Chiba University Hospital, Chiba, Japan.
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Oh SY, Ryoo BY, Kim WS, Park YH, Kim K, Kim HJ, Kwon JM, Lee J, Ko YH, Ahn YC, Oh SJ, Lee SI, Kim HJ, Kwon HC, Bang SM, Kim JH, Park J, Lee SS, Kim HY, Park K. Nongastric marginal zone B-cell lymphoma: analysis of 247 cases. Am J Hematol 2007; 82:446-52. [PMID: 17266060 DOI: 10.1002/ajh.20874] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Nongastric marginal zone B-cell lymphoma (NG-MZL) is a relatively uncommon indolent lymphoma. From 1990 to 2005, a total of 247 patients with histologically confirmed NG-MZL were analyzed. Ann Arbor stage I/II disease was present in 78% (167 out of 215). One hundred eighty-six patients out of two hundred eight were categorized into the low/low-intermediate risk group (89%) according to International Prognostic Index (IPI). Eighty percent (172/215) were in low risk group according to Follicular Lymphoma International Prognostic Index (FLIPI). Complete and partial remissions (CR and PR) were achieved in 140 (92.7%) and 8 (5.3%) of the 151 stage I/II patients. Especially, radiation containing treatment achieved 96% CR rate (108 out of 113). In 38 patients with stage III/IV, CR and PR were achieved in 17 (44.7%) and 11 (26.3%), respectively. The estimated five-year overall survival (OS) and progression-free survival (PFS) were 93.8% and 70.1%, respectively. Although anthracycline-containing regimen could achieve higher CR rate, it did not improve PFS. Stage III/IV, low hemoglobin, poor performance status, high/high-intermediate IPI, poor risk FLIPI, and nodal MZL were poor prognostic factors for PFS. NG-MZL is an indolent disease. FLIPI has strong power to predict the prognosis of NG-MZL.
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Affiliation(s)
- Sung Yong Oh
- Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Arndt S, Veelken H, Schmitt-Gräff A, Aschendorff A, Maier W, Richter B. Multifocal extranodal mucosa-associated lymphoid tissue lymphoma affecting the larynx. Ann Otol Rhinol Laryngol 2007; 116:257-61. [PMID: 17491523 DOI: 10.1177/000348940711600406] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES Extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) accounts for about 7% to 8% of all B-cell lymphomas and 50% of all gastric lymphomas. Long-term localized growth is typical of MALT lymphoma. Multifocal manifestations are possible in advanced stages. MALT lymphoma of the larynx is a very rare disease; only 15 cases have been reported in the literature. METHODS We report a case of multifocal MALT lymphoma affecting the larynx associated with extraesophageal reflux, chronic laryngitis, and gastric Helicobacter pylori infection. The staging revealed a recurrent tumor of MALT lymphoma in the stomach and an involvement of the right conjunctiva. RESULTS Following recent reports on successful treatment of MALT lymphoma with antibiotics, initial empirical therapy with doxycycline calcium led to a subjective clinical symptom improvement but no objective response as assessed by laryngoscopy, magnetic resonance imaging of the larynx, and esophagogastroduodenal endoscopy. Because of the advanced stage and multiple extranodal manifestations of the MALT lymphoma, the patient received 3 cycles of chemoimmunotherapy according to the FCR protocol (fludarabine phosphate-cyclophosphamide-rituximab). No evidence of disease was observed after a 6-month follow-up. CONCLUSIONS In the rare diagnosis of MALT lymphoma of the larynx, comprehensive staging is indispensable to exclude multifocal involvement. In contrast to the treatment of primarily localized MALT lymphoma, multifocal disease warrants systemic therapy.
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MESH Headings
- Adult
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Agents/therapeutic use
- Cyclophosphamide/therapeutic use
- Diagnosis, Differential
- Drug Therapy, Combination
- Endoscopy, Gastrointestinal
- Female
- Follow-Up Studies
- Humans
- Laryngeal Neoplasms/diagnosis
- Laryngeal Neoplasms/drug therapy
- Laryngeal Neoplasms/surgery
- Laryngoscopy
- Lymphoma, B-Cell, Marginal Zone/diagnosis
- Lymphoma, B-Cell, Marginal Zone/drug therapy
- Lymphoma, B-Cell, Marginal Zone/surgery
- Magnetic Resonance Imaging
- Rituximab
- Vidarabine Phosphate/analogs & derivatives
- Vidarabine Phosphate/therapeutic use
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Affiliation(s)
- Susan Arndt
- Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Freiburg, Germany
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Raderer M, Wohrer S, Streubel B, Drach J, Jager U, Turetschek K, Troch M, Puspok A, Zielinski CC, Chott A. Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone in patients with relapsed MALT lymphoma. Oncology 2007; 70:411-7. [PMID: 17220639 DOI: 10.1159/000098555] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2006] [Accepted: 10/14/2006] [Indexed: 12/12/2022]
Abstract
BACKGROUND Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far. Judging from the data obtained in various types of lymphoma, the activity of R appears to be enhanced by combination with chemotherapy. As no data on this topic exist for MALT lymphoma, we have retrospectively analysed our experience with R plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R-CHOP/R-CNOP) in patients with relapsed MALT lymphoma. PATIENTS AND METHODS A total of 26 patients were identified, 15 were administered R-CHOP while 11 patients were given R-CNOP due to age >65 years or pre-existing cardiac conditions. Cycles were repeated every 21 days, and restaging was performed after 4 cycles of therapy. In case of complete remission, 2 further cycles were administered for consolidation while patients achieving partial remission or stable disease after restaging were given 4 further courses. RESULTS A total of 170 cycles were administered to our patients (median 6, range 2-8). Twenty of the 26 patients (77%) achieved a complete remission and 6 (23%) a partial remission. Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia occurring in 5 patients. After a median follow-up of 19 months (range 10-45), all patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12 and 19 months after treatment. CONCLUSIONS Our data demonstrate a high activity of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.
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Affiliation(s)
- Markus Raderer
- Department of Internal Medicine I, University of Vienna, Vienna, Austria.
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Tsai HK, Li S, Ng AK, Silver B, Stevenson MA, Mauch PM. Role of radiation therapy in the treatment of stage I/II mucosa-associated lymphoid tissue lymphoma. Ann Oncol 2007; 18:672-8. [PMID: 17218489 DOI: 10.1093/annonc/mdl468] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Few large studies exist on the outcome of patients treated for stage I/II mucosa-associated lymphoid tissue (MALT) lymphoma. PATIENTS AND METHODS We retrospectively reviewed the records of 77 patients consecutively treated for stage I (n = 66) or II (n = 11) MALT lymphoma at our institution. Progression-free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS The median follow-up time was 61 months (range 2-177 months). Fifty-two patients (68%) received local radiation therapy (RT) alone, 17 (22%) had surgery followed by adjuvant RT, five (6%) had surgery alone, two (3%) had surgery and chemotherapy, and one patient had chemotherapy alone. The median RT dose was 30 Gy (range 18-40 Gy). The 5-year PFS, FFTF, and OS rates were 76%, 78%, and 91%, respectively. The 5-year PFS (79% versus 50%; P = 0.002) and FFTF (81% versus 50%; P = 0.0004) rates were higher for patients who received RT as compared with patients who did not. CONCLUSIONS The prognosis following treatment of stage I/II MALT lymphoma is excellent. RT improves PFS and FFTF and has an important role in the curative treatment of patients with localized disease.
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Affiliation(s)
- H K Tsai
- Harvard Radiation Oncology Program, 75 Francis Street, Boston, MA 02115, USA
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Papiris SA, Kalomenidis I, Malagari K, Kapotsis GE, Harhalakis N, Manali ED, Rontogianni D, Roussos C, Moutsopoulos HM. Extranodal marginal zone B-cell lymphoma of the lung in Sjögren's syndrome patients: Reappraisal of clinical, radiological, and pathology findings. Respir Med 2007; 101:84-92. [PMID: 16735112 DOI: 10.1016/j.rmed.2006.04.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2005] [Revised: 03/07/2006] [Accepted: 04/16/2006] [Indexed: 01/15/2023]
Abstract
BACKGROUND Primary Sjögren's syndrome (pSs) is an autoimmune rheumatic disease that may express in a small number of patients a spectrum of lymphoproliferative diseases. The aim of this study was to describe clinical, imaging and pathology features of the extranodal marginal zone B-cell lymphoma (MZCL) of the lung of mucosa-associated lymphoid tissue (MALT) type in patients with pSs. METHODS All patients (N=10) with biopsy proven MZCL of the lung of MALT type diagnosed in a tertiary teaching hospital during the last 7 years were studied. RESULTS Seven patients had pSs. Almost all patients presented an indolent clinical course, contrasting strongly with the spectacular radiological findings in both chest roentgenograms and computed tomography. Pathology infiltration patterns observed were either nodular, peribronchial-perivascular, alveolar, or interstitial. Immunohistochemical study in all cases showed B cell phenotypes. Immunoglobulin light chain restriction was demonstrated in all patients. Monoclonal IgM(kappa) was evident in 5/7, IgM(lambda) in 1/7 and IgG (kappa) in 1/7 of patients. CONCLUSIONS Lung MZCL associated with pSs are characterized by an important dissociation between clinical expression and radiological pattern. Clinical presentation and imaging features are not specific. Therefore, histologic documentation is mandatory to ensure diagnosis. Various chemotherapeutic agents in combination with rituximab lead to partial or complete remission in the majority of patients.
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MESH Headings
- B-Lymphocytes/pathology
- Biomarkers/analysis
- CD4-Positive T-Lymphocytes/pathology
- Female
- Humans
- Immunohistochemistry/methods
- Keratins/analysis
- Lung/diagnostic imaging
- Lung/pathology
- Lymphoma, B-Cell/complications
- Lymphoma, B-Cell/diagnostic imaging
- Lymphoma, B-Cell/pathology
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/diagnostic imaging
- Lymphoma, B-Cell, Marginal Zone/pathology
- Male
- Sjogren's Syndrome/complications
- Sjogren's Syndrome/diagnostic imaging
- Sjogren's Syndrome/pathology
- Tomography, X-Ray Computed
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Affiliation(s)
- Spyros A Papiris
- 2nd Pulmonary Department, Attikon University Hospital, 1 Rimini Street, 12462 Haidari, Athens, Greece.
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Ferrucci PF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years? Br J Haematol 2006; 136:521-38. [PMID: 17156403 DOI: 10.1111/j.1365-2141.2006.06444.x] [Citation(s) in RCA: 93] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Primary gastric (PG) lymphomas are generally non-Hodgkin lymphomas (NHL). They represent 5% of gastric malignancies and show an apparently increasing incidence worldwide. The most common histological subtypes are diffuse large B-cell and marginal zone B-cell NHL of the mucosa-associated lymphoid tissue (MALT)-type. Pathogenesis is often related to Helicobacter pylori infection (HPI). There is still no consensus on the optimal treatment for PG lymphoma. Nowadays surgery is limited to rare cases and radiotherapy--combined or not with chemotherapy--represents an effective therapeutic option ensuring long-term, organ-salvage benefits mainly in aggressive histological subtypes. Additionally, the description of MALT lymphomas has made the situation even more complex, because antibiotics alone can induce lasting remissions in those cases associated with HPI. Consequently, a global therapeutic approach to the cure of PG-NHL has completely changed over the last 10 years: innovative, conservative options to reduce treatment toxicity, thus preventing systemic relapses, have made their appearance and are on the rise.
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MESH Headings
- Helicobacter Infections/complications
- Helicobacter pylori
- Humans
- Lymphoma, B-Cell/diagnosis
- Lymphoma, B-Cell/etiology
- Lymphoma, B-Cell/therapy
- Lymphoma, B-Cell, Marginal Zone/diagnosis
- Lymphoma, B-Cell, Marginal Zone/etiology
- Lymphoma, B-Cell, Marginal Zone/therapy
- Lymphoma, Non-Hodgkin/diagnosis
- Lymphoma, Non-Hodgkin/etiology
- Lymphoma, Non-Hodgkin/therapy
- Stomach Neoplasms/diagnosis
- Stomach Neoplasms/etiology
- Stomach Neoplasms/therapy
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