Role of Rituximab in the Treatment of Splenic Marginal Zone Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4694-4694
Author(s):  
Saaib Al Shehadat ◽  
Martin A. Bast ◽  
Gene Sehi ◽  
Greory R. Bociek ◽  
Anne Kessinger ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Complete Remission ◽  
Lymph Nodes ◽  
Marginal Zone ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Cytotoxic Agents ◽  
Aggressive Lymphoma ◽  
Splenic Marginal Zone Lymphoma

Abstract Background: Splenic marginal zone lymphoma (SMZL) is a rare malignancy accounting for less than 1% of all lymphomas. The tumor involves the spleen, splenic hilar lymph nodes, bone marrow, and often the peripheral blood. The peripheral lymph nodes are not typically enlarged. Patients typically have circulating neoplastic cells characterized by cytoplasmic projections, round or oval nuclei and clumped chromatin. The lymphoma cells express CD19, CD20, and CD22 but not usually CD5, CD10, CD23, CD25, CD43, CD103 or cyclin D1. The tumor may be surprisingly resistant to chemotherapy that would ordinarily be effective for chronic lymphocytic leukemia. For patients needing treatment, splenectomy is the usual first treatment, which may be followed by prolonged remission. The best approach for patients following splenectomy is not clear. Methods: The characteristics of seven patients with SMZL who progressed after splenectomy are shown in the table. Six of the seven patients received rituximab therapy alone or in combination with other cytotoxic agents. One patient was ineligible for rituximab therapy due to hepatitis C. Results: One patient who relapsed 16 months after splenectomy to diffuse large B cell lymphoma (DLBCL) achieved a complete remission after 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and then electively underwent autologous peripheral stem cell transplantation. His remission persisted 72+ months later. The two patients who received rituximab in combination with other cytotoxic agents 2 months after splenectomy (one had CNOP/cyclophosphamide, mitoxantrone, vincristine, and prednisone; and one had CVP/cyclophosphamide, vincristine, prednisone) remained in remission 52+ months. One patient with anemia refractory to splenectomy responded to 4 cycles of rituximab. One patient who developed anemia and monoclonal gammopathy post splenectomy received 8 weekly cycles of rituximab. Although anemia improved there was no objective response. One patient’s disease transformed to DLBCL 18 months post splenectomy, and did not respond to 8 cycles of rituximab. Conclusion: These results suggest that SMZL in patients who relapsed after splenectomy transforms to aggressive lymphoma more commonly than several thought. Most patients respond to rituximab containing regimens and may achieve a prolonged remission. More studies are warranted to investigate whether rituximab therapy shortly after splenectomy provides better progression free survival than treatment after relapse. Patients’ Characteristics 1 2 3 4 5 6* 7 F: female, CR: complete remission, M: male, P: progression, PR: partial remission, * Hepatitis C. Age 62 33 53 53 67 55 67 Sex M M F F F M F Year 1997 1998 2000 2001 2001 2001 2002 CD20 + + + + + + + DLBCL Transformation + - - - - - + Rituximab # of Cycles 6 8 4 4 6 0 8 Concurrent Chemotherapy CHOP CNOP - Fludarabine CVP CHOP - Response CR CR CR PR CR CR P Follow up (Months) 72+ 61+ 49+ 50+ 50+ 52+ 0

Outcomes In Splenic Marginal Zone Lymphoma: Analysis Of 108 Patients Treated In British Columbia (BC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4369-4369
Author(s):  
Katharine He Xing ◽  
Amrit Kahlon ◽  
Joseph M. Connors ◽  
Brian Skinnider ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
British Columbia ◽  
Hepatitis C ◽  
Research Funding ◽  
Marginal Zone ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Transformation Rate ◽  
Splenic Marginal Zone Lymphoma ◽  
First Line

Abstract Introduction Splenic marginal zone lymphoma (SMZL) is uncommon and accounts for less than 1% of all non-Hodgkin lymphomas. The optimal treatment for SMZL is unknown. We describe the outcome of 108 patients with SMZL treated in British Columbia. Methods All patients with SMZL diagnosed between 1985 and June 2012 were identified in the BC Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Overall survival (OS) was measured from time of diagnosis to death or last follow-up. Progression-free survival (PFS) was measured from the date of diagnosis to the date of lymphoma recurrence or transformation, or death. Time to transformation (TTT) was calculated from date of diagnosis to date of transformation to aggressive lymphoma. Results 108 patients were identified with a diagnosis of SMZL. Baseline patient characteristics: median age 67 years (range 30-88), male 41%, stage IV 98%, B symptoms 17%, performance status ≥2 22%, splenomegaly 93%, bone marrow involvement 93%, peripheral blood involvement 87%. Hepatitis C serology was positive in 5 of 60 patients with available data. As initial treatment, 53 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 with a rituximab-containing regimen), 2 received antiviral therapy for hepatitis C, and 15 were observed. Of the 43 patients who had splenectomy alone, 9 subsequently received chemotherapy upon progression, 1 had excision for a soft tissue mass, and 4 transformed to diffuse large B cell lymphoma (DLBCL). Of the 38 who received chemotherapy first line, 6 subsequently received combined chemotherapy and splenectomy, 1 splenectomy alone, 4 chemotherapy alone, and 7 transformed to DLBCL. Neither of the 2 patients who received antivirals had further progression. With a median follow-up of 7 years (range 3 months to 18 years) for living patients, the 5 and 10 year OS were 65% and 48%, respectively. The 5 and 10 year PFS were 38% and 18%, respectively. The 5 year OS for patients who had a splenectomy as their first-line therapy compared to other treatments was 76% vs 53% (p=0.01); and the 5 year OS for patients who received chemotherapy alone as first-line compared to other treatments was 52% vs 72% (p=0.04). There was no difference in outcomes between those treated with rituximab containing chemotherapy as first line compared to other treatments (p=0.65). The 5 and 10 year PFS after first-line splenectomy were 52% and 18%, respectively. A total of 14 patients transformed to DLBCL with a median TTT of 3.2 years (range 6 months to 11.9 years). The 5, 10, 15 year rates of transformation were 9%, 21% and 35%, respectively. Conclusions Splenectomy remains a reasonable treatment option for patients with SMZL. Patients selected for splenectomy as initial management of symptomatic disease experience improved outcomes. The transformation rate in SMZL is similar to that of other indolent lymphomas. Disclosures: Connors: F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Skinnider:Roche Canada: Research Funding. Gascoyne:Roche Canada: Research Funding. Sehn:Roche Canada: Research Funding. Savage:Roche Canada: Research Funding. Slack:Roche Canada: Research Funding. Shenkier:Roche Canada: Research Funding. Klasa:Roche Canada: Research Funding. Gerrie:Roche Canada: Research Funding. Villa:Roche Canada: Research Funding.

Splenic Marginal Zone Lymphoma Shows a Distinct Pattern of DNA Copy Number Aberrations That Correlates with Tumor Characteristics and Predicts Disease Outcome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2422-2422
Author(s):  
Jose A. Martinez-Climent ◽  
Cristina Robledo ◽  
Manuela Mollejo ◽  
Anton Parker ◽  
Juan L. Garcia ◽  
...  
Keyword(s):  
B Cell ◽  
Copy Number ◽  
Marginal Zone ◽  
Array Cgh ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Genomic Aberrations ◽  
7Q Deletion

Abstract Splenic marginal zone lymphoma (SMZL) is an indolent B cell malignancy whose diagnosis is based on lymphocyte morphology, immunophenotype and marrow and/or splenic histology. Unlike other lymphomas, there is not a common chromosomal translocation specific for SMZL, and genetic prognostic factors are poorly defined. To investigate the pattern of genomic aberrations in SMZL, we applied comparative genomic hybridization to BAC microarrays (array CGH) to a well characterized series of 75 SMZL specimens. We applied two different 1 Mb-resolution BAC arrays: UCSF HumArray 3.2 and a novel array CGH platform developed at Univ. of Salamanca. These arrays allowed us to detect DNA copy number changes across the genome with high accuracy in 67 of 75 patient samples. Data were compared with our previous array CGH studies of 170 samples from different B-cell lymphoma subgroups. FISH studies for IGH, IGK and IGL translocations and 7q deletion were performed on tissue microarrays in 24 cases. Of the 67 samples, 19 (28%) showed a normal genomic profile. The median number of genomic aberrations per tumor was 2.2 (1.3 gains and 0.9 losses), which was lower than the rates detected in other lymphoma subgroups (diffuse large cell lymphoma, 6.4; mantle cell lymphoma, 6; follicular lymphoma, 4.5) and comparable to MALT lymphomas (2 abnormalities per tumor). SMZL cells showed a genomic pattern characterized by gain of chromosomes 3q24-q29 (18%), 6p (9%), 12q (9%), and 18q (4%) and loss of 7q32 (34%), 8p21-p23 (13%), 17p13 (10%) at P53 locus and 6q21-q27 (9%). Notably, no alterations of the P16/ARF (9p21) or MYC loci (8q24) were detected. Correlation of array CGH data with conventional cytogenetics, FISH and LOH studies revealed a high concordance. Detailed mapping of 7q deletions delineated a consensus region of loss of 3 Mb in 7q32. This 7q deletion was almost exclusive to SMZL, being observed in only 5 of 170 non-SMZL B-cell lymphomas (p=0.0000001). Four cases presented IG-translocation. Mutation of IGH was observed in 62% and correlated with a complex karyotype (61 vs. 13%; p=0,0008) whereas unmutated IGH correlated with the deletion of 7q (56 vs. 23%; p=0,01). Among the various genomic abnormalities, only the deletion of 8p or the presence of a complex karyotype correlated with inferior overall survival (OS) (median OS, 58 vs. 110 months, p=0,004; and 60 vs. 105 months, p=0,01; respectively). In summary, array CGH has defined a pattern of genomic aberrations in SMZL that differs from other B-cell lymphoma subgroups and that may predict overall survival. Because the deletion of 7q32 is the most distinctive genetic marker in SMZL, the identification of a putative tumor suppressor gene inactivated within the region of deletion seems mandatory.

Splenectomy Is Still a Valid Option For Splenic Marginal Zone Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5129-5129
Author(s):  
Alessandro Pulsoni ◽  
Pasqualina D'Urso ◽  
Gianna Maria D'Elia ◽  
Giorgia Annechini ◽  
Caterina Stefanizzi ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Spleen Size ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Introduction Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoma characterized by splenomegaly, frequent moderate lymphocytosis with or without villous morphology and possible involvement of various organs, especially the bone marrow (BM). Diagnosis is classically based on the spleen histology, but it can be made on the BM biopsy, based on the typical intrasinusoidal cell infiltration pattern and immunohistochemistry. Different therapeutic options are available, but to date there are no conclusive comparative data. Patients and methods We retrospectively analyzed 83 consecutive patients with a diagnosis of SMZL observed at our Institution between 1999 and 2013. The diagnosis was based on the BM biopsy in 79 patients; the BM was negative in 4 patients. Diagnosis was histologically confirmed on the spleen in 27 patients who underwent splenectomy. Patients presented a median age of 72.5 years (range 38-84); 43 were males. The median spleen size at diagnosis was 145 mm, ranging from 100 to 300 mm. The majority of patients were stage IV at diagnosis for BM infiltration (95%); B symptoms were present in 4 of them (4.8%). Forty-two patients (50.6%) had a lymphocytosis at diagnosis and 13 (15.6%) presented an IPI score higher than 3. Thirty-five of them (42%) had a MZL BM infiltration superior to 30% of the total bone cellularity. Forty-two patients (50.6%) underwent a watch and wait policy (WW), while 41 (49.4%) were treated within 6 months from diagnosis, mainly because of symptomatic splenomegaly; in these patients, treatment consisted of splenectomy, chemotherapy or chemotherapy plus immunotherapy with Rituximab. The features of patients submitted to WW with respect to patients treated at diagnosis were comparable for the various parameters mentioned above, except for spleen size (higher in patients treated at presentation) and lymphocyte count (higher in patients who were observed). After a median follow-up of 64 months, the overall median survival was 96%. Among the 42 WW patients, 18 (42.8%) are still untreated after a median follow-up of 57.5 months, while 24 (57.2%) have required therapy; the median treatment-free interval in these patients was 25.5 months. Concerning the 41 patients who underwent treatment at diagnosis, after a median follow-up of 50 months, 13 (31.7%) have required a subsequent second-line treatment. The interval between first-line approach and re-treatment in patients treated at diagnosis was 30 months. Overall, 27 patients were treated with splenectomy only (either at diagnosis or after a WW period): only 6 of them (22%) had a subsequent progression after a median latency of 42 months; 26 were treated with chemotherapy alone (alkylating agents in the majority of them, combination therapy in a minority): 15 of them (60%) had a subsequent relapse or progression after a median of 9 months; 12 patients received a Rituximab-containing regimen: of these, only 2 (16%) have so far required a second-line therapy after 10 and 26 months respectively. Conclusions The WW policy is a valid option for asymptomatic patients: in these patients, after 4.5 years from diagnosis more than 40% is still untreated. In patients requiring treatment, splenectomy alone is followed in the majority of patients by a long period of good disease control: only 22% required a second-line therapy after 3.5 years. The addiction of Rituximab to chemotherapy seems to reduce the probability of relapse and to prolong the response duration. However, these preliminary data need to be confirmed by larger studies. Disclosures: No relevant conflicts of interest to declare.

Deregulated PAX-5 Transcription From a TranslocatedIgH Promoter in Marginal Zone Lymphoma

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3865-3878 ◽  
Author(s):  
Aline M. Morrison ◽  
Ulrich Jäger ◽  
Andreas Chott ◽  
Michael Schebesta ◽  
Oskar A. Haas ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Marginal Zone ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Chain Gene ◽  
Splenic Marginal Zone Lymphoma ◽  
Derivative Chromosome ◽  
B Cell Differentiation ◽  
Loss Of Function

Abstract The PAX-5 gene codes for the transcription factor BSAP, which is expressed throughout B-cell development. Although loss-of-function mutation in the mouse showed an essential role forPax-5 in early B lymphopoiesis, gain-of-function mutations have implicated the human PAX-5 gene in the control of late B-cell differentiation. PAX-5 (on 9p13) has been involved together with the immunoglobulin heavy-chain (IgH) gene (on 14q32) in the recurring t(9;14)(p13;q32) translocation that is characteristic of small lymphocytic lymphoma with plasmacytoid differentiation. Here we have characterized a complex t(2;9;14)(p12;p13;q32) translocation present in a closely related non-Hodgkin’s lymphoma referred to as splenic marginal zone lymphoma (MZL). In this MZL-1 translocation, the two promoters of PAX-5 were replaced on the derivative chromosome 14 by an immunoglobulin switch Sμ promoter that was linked to the structural PAX-5 gene upstream of its translation initiation codon in exon 1B. Expression analyses confirmed thatPAX-5 transcription was upregulated due to efficient initiation at the Sμ promoter in the malignant B lymphocytes of patient MZL-1. For comparison we have analyzed PAX-5 expression in another B-cell lymphoma, KIS-1, indicating that transcription from the distalPAX-5 promoter was increased in this tumor in agreement with the previously characterized translocation of the immunoglobulin Eμ enhancer adjacent to PAX-5 exon 1A. In both lymphomas, the J-chain gene, which is thought to be under negative control by BSAP, was not expressed, whereas transcription of the putative target genep53 was unaffected by PAX-5 overexpression. Together these data indicate that the t(9;14)(p13;q32) translocation contributes to lymphoma formation as a regulatory mutation that leads to increasedPAX-5 expression in late B-cell differentiation due to promoter replacement or enhancer insertion.

Mortality and Transformation Risk-Factors in Hepatitis C Negative Splenic Marginal Zone Lymphoma

2019 ◽  
Vol 19 ◽  
pp. S311
Author(s):  
Sergio Brasil ◽  
Jamilla Cavalcante ◽  
Maria Purini ◽  
Roberto Paes ◽  
Rodolfo Cancado
Keyword(s):  
Risk Factors ◽  
Hepatitis C ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma
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