scholarly journals LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2423-2427 ◽  
Author(s):  
C Bastard ◽  
C Deweindt ◽  
JP Kerckaert ◽  
B Lenormand ◽  
A Rossi ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Frequent Event

Abstract We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.

scholarly journals LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2423-2427 ◽  
Author(s):  
C Bastard ◽  
C Deweindt ◽  
JP Kerckaert ◽  
B Lenormand ◽  
A Rossi ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Frequent Event

We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.

scholarly journals Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin’s lymphoma

2021 ◽  
Vol 9 (2) ◽  
pp. e002097
Author(s):  
Kathryn Lurain ◽  
Ramya Ramaswami ◽  
Ralph Mangusan ◽  
Anaida Widell ◽  
Irene Ekwede ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hiv And Aids ◽  
Hodgkin's Lymphoma ◽  
People Living With Hiv ◽  
Oncogenic Viruses ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

BackgroundNon-Hodgkin’s lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.MethodsWe conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.ResultsWe identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1–21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2–3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.ConclusionsTreatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

scholarly journals Case of extranodal non-hodgkins lymphoma involving the endometrium and the ovaries: a rare case report

2017 ◽  
Vol 6 (9) ◽  
pp. 4131 ◽  
Author(s):  
Lakshmi Manjeera Malempati ◽  
Neetha Nandan ◽  
Sagarika Babu
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Female Genital Tract ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Western World ◽  
Non Hodgkin’S Lymphoma ◽  
Uterine Neoplasm ◽  
Non Hodgkin's Lymphoma ◽  
Large B Cell

Non-Hodgkin’s lymphoma(NHL) is most commonly encountered during childhood and rarely among the adults. Primary malignant lymphoma in the female genital tract are rare Moreover they present with non-specific symptoms and hence there may be delay in the diagnosis. It is difficult to distinguish this condition from the more common uterine neoplasm such as uterine fibroids or sarcoma. Diffuse large B-cell lymphoma (DLBCL) is most commonly seen among the cases of NHL, contributing to among one third of NHL in the western world. DLBCL is common in elderly population. A 69-year-old postmenopausal woman who came with watery discharge since, 15 days was evaluated clinically and radiologically and was found to have thickened endometrium and enlarged ovaries, for which endometrial biopsy was taken that showed non-secretory endometrium with atrophic changes. Tumor markers found to be normal. TAH+BSO was done and the histopathology showed Non-Hodgkin’s lymphoma, diffuse large B cell type of the endometrium and both ovaries which was confirmed by immune histochemical marker study. PET-CT was done that showed metabolically active para aortic and common iliac lymph nodes thereby she was diagnosed with stage II (Ann Arbor Staging) non-Hodgkin’s lymphoma, hence she received 6 cycles of R-CHOP. As evident in our case, non-Hodgkin’s Lymphoma of the endometrium and the ovaries being an extremely rare condition, high-degree of suspicion is required for its prompt diagnosis and treatment.

CERA (Continuous Erythropoietin Receptor Activator): Dose-Response Trial of Subcutaneous (SC) Administration Once Every 3 Weeks (Q3W) to Patients with Aggressive Non-Hodgkin’s Lymphoma and Anemia Receiving Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4225-4225 ◽  
Author(s):  
Anders Osterborg ◽  
Andrzej Hellmann ◽  
Stephen Couban
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Dose Response ◽  
Combination Chemotherapy ◽  
Hodgkin’S Lymphoma ◽  
Transferrin Saturation ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract CERA is an erythropoiesis-stimulating agent (ESA) acting differently at the receptor level with a prolonged half-life. In this ongoing, multicenter, randomized, open-label, Phase II dose-response study, CERA was administered subcutaneously in a Q3W schedule to 93 transfusion-independent patients with aggressive (intermediate or high grade) B-cell non-Hodgkin’s lymphoma (NHL) and anemia receiving combination chemotherapy. Eligible patients met the following inclusion criteria: age ≥18 years, hemoglobin (Hb) <11 g/dL, combination chemotherapy scheduled to be administered throughout the 12-week treatment period, life expectancy >6 months, and Eastern Cooperative Oncology Group (ECOG) performance status grade 0–2. Major exclusion criteria included transferrin saturation <20% and platelet count <50 x 109/L. No patient had received an ESA in the 8 weeks prior to the first dose of CERA. Patients were randomized to receive CERA 2.1 μg/kg (n=31), 4.2 μg/kg (n=30), or 6.3 μg/kg (n=32) administered once every 3 weeks for 12 weeks. The primary efficacy variable was time-adjusted average change in Hb from baseline during 12 weeks, until end of initial treatment (last observed value before dose change or transfusion). Enrollment has been completed; the treatment phase of the trial is nearing conclusion. Demographics show similar baseline characteristics in all three patient subgroups [mean age: 62.9 years (2.1 μg/kg); 59.1 years (4.2 μg/kg); 64.3 years (6.3 μg/kg)]. Diffuse large B-cell lymphoma was the most common lymphoma in all three subgroups (87%, 70%, and 84% of patients in the 2.1, 4.2, and 6.3 μg/kg subgroups, respectively). To date, the majority of patients receive an anthracycline-containing chemotherapy regimen, either standard CHOP or CHOP plus rituximab. Preliminary efficacy and safety results will be presented. Ongoing assessments have indicated a safety profile consistent with that seen in patients with aggressive NHL and anemia receiving chemotherapy. This Phase II trial will help further characterize the ability of CERA to safely correct anemia when administered at an extended dosing interval (Q3W) to patients with aggressive NHL receiving chemotherapy.

Preclinical Safety and Efficacy of Two Novel Immunotoxins Consisting of Ranpirnase (Rap) Fused to an Internalizing Anti-CD74 Humanized IgG4 Antibody in Human Non-Hodgkin’s Lymphoma Xenografts.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 346-346 ◽  
Author(s):  
Puja Sapra ◽  
Chien-Hsing Chang ◽  
Sailaja Vanama ◽  
Sharon Singh ◽  
Hans J. Hansen ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Specific Binding ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Therapeutic Effects ◽  
Single Chain ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Recombinant Immunotoxins

Abstract Rap, an amphibian ribonuclease, is a single-chain protein of 104 amino acids that kills cells by degrading t-RNA upon internalization. CD74 is a rapidly internalizing type-II transmembrane chaperone molecule associated with HLA-DR, and has high expression on hematological malignancies including B-cell non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). We have constructed and evaluated two novel immunotoxins, 2L-Rap-hLL1-γ 4P and 2L-Rap(N69Q)-hLL1-γ 4P, each composed of two Rap molecules fused to hLL1, an internalizing anti-CD74 humanized monoclonal antibody. The Rap gene was inserted at the N-terminus of the light chain in the expression vector of hLL1 and expressed in NS0 mouse myeloma cells. To reduce unwanted cytotoxicity, the CH1, CH2, CH3 and the hinge regions of the γ 1 chain of hLL1 were replaced with those of γ 4. Additionally, the serine residue in the hinge region was converted to proline to prevent the formation of IgG4 half-molecules. Noting that Rap contains a potential N-glycosylation site at the 69th residue of asparagine(N69), a variant of Rap, referred to as Rap(N69Q), was constructed by changing N to Q (glutamine) and this variant was used to make 2L-Rap(N69Q)-hLL1-γ 4P. Purified recombinant immunotoxins were shown to be a single peak by SE-HPLC and their MW determined by MALDI-TOF to be 177,150, which is in agreement with the MW of one IgG (150,000) plus two Rap molecules (24,000). In vitro, both immunotoxins retained RNase activity, specific binding to CD74, and were significantly more potent against CD74-positive NHL and MM cell lines (Daudi, Raji and MC/CAR) than naked hLL1 or non-specific control immunotoxin, 2L-Rap(N69Q)-hRS7(immunotoxin against EGP-1). In Raji and Daudi Burkitt’s lymphoma xenograft models, treatment with a single 5- to 50-μg dose of 2L-Rap-hLL1-γ 4P, given as early or delayed treatment, resulted in cures of most animals. Additionally, treatment with a single 15-μg dose of 2L-Rap(N69Q)-hLL1-γ 4P 1-day post injection of cells resulted in 100% cures. Treatment with 2L-Rap-hLL1-γ 4P or 2L-Rap(N69Q)-hLL1-γ 4P was significantly better than all controls, including saline, naked hLL1 and non-specific immunotoxin. The maximum tolerated dose of 2L-Rap-hLL1-γ 4P or 2L-Rap(N69Q)-hLL1-γ 4P in SCID or BALB/c mice was 50 μg/mouse and the dose-limiting toxicity was hepatic. In our preliminary studies, we have observed that treating animals with NSAID’s, such as indomethacin, can ameliorate the hepatoxicity of 2L-Rap-hLL1-γ 4P. All animals that were injected with 100 μg/mouse 2L-Rap-hLL1-γ 4P alone died with a median survival time of 7 days; however, animals treated with 1.25mg/kg indomethacin prior and post-treatment of 2L-Rap-hLL1-γ 4P survived the duration of study (day 40). Experiments to determine the possible causes of liver toxicity produced by 2L-Rap-hLL1-γ 4P and to determine the MTD of Rap-immunotoxins in mice after treatment with indomethacin are ongoing. In conclusion, we have constructed two CD74-targeted novel recombinant immunotoxins containing Rap molecules that have demonstrated curative therapeutic effects in animal models of human B-cell lymphoma, and thus could be potential therapeutics for CD74-postive lymphomas and myelomas.

Clinical Features and Prognostic Relevance of Ovarian Involvement in Non-Hodgkin's Lymphoma: a Consortium for Improving Survival of Lymphoma (CISL) Report.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4999-4999
Author(s):  
Jina Yoon ◽  
Seok Jin Kim ◽  
Jong Ho Won ◽  
Chul Won Choi ◽  
Hyeon-Seok Eom ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Disseminated Disease ◽  
Ovarian Involvement

Abstract Abstract 4999 Introduction Ovary can be involved as a primary ovarian lymphoma or secondarily involved by disseminated disease of non-Hodgkin's lymphoma. However, ovarian involvement is an extremely rare event in non-Hodgkin's lymphoma. Thus, it clinical features and prognostic relevance has rarely been addressed, and most publications refer to a single or a few cases. Thus, we retrospectively analyzed patients with ovarian involvement Patients and methods 32 patients with ovarian involvement were assembled from 8 hospitals affiliated with the CISL (Consortium for Improving Survival of Lymphoma), a Korean lymphoma study group. Primary ovarian involvement was defined as a lymphoma confined to ovary with or without involvement of adjacent lymph nodes and contiguous organs. Secondary ovarian lymphoma was defined as a secondary involvement of ovary in disseminated disease of lymphoma at initial diagnosis. Results Twelve patients had primary ovarian lymphoma (37.5%) while twenty patients (62.5%) had secondary ovarian involvement by systemic disease. The clinical manifestations of ovarian involvement were similar to that of other ovarian tumors, namely an abdominal pain (31%), abdominal distension (19%) or lower abdominal palpable mass (16%). Pathological review according to the WHO classification showed that the most common histological subtype was diffuse large B-cell lymphoma (DLBCL, 75.0%, 24/32), and the frequency of other subtypes was as follows: Burkitt lymphoma (BL, 12.5%, 4/32), lymphoblastic lymphoma (6.3%, 2/32), marginal zone B-cell lymphoma (MZL, 3.1%, 1/32), peripheral T-cell lymphoma, unspecified (PTCL-U, 3.1%, 1/32). The median age (43 years, range 18-80) was younger than that of previously reported other organs such as uterus or prostate. The presence of B symptoms was only observed in 31.3%, and the performance status was good (84.4% of patients had less than grade II of ECOG performance status). The cases involving two or more than two extranodal sites were 68.8% while cases with elevated level of serum LDH were 59.4%. Thus, 59.4% of patients had the low or low-intermediate score of IPI score. Bilateral ovarian involvement was found in 12/32 (38%) while unilateral involvement was 20/32 (63%, 9 right and 11 left side. Three patients showed the involvement of central nervous system (CNS) at diagnosis (3/32, 9.4%). These three patients had DLBCL histology and unfavorable parameters including stage IV, high IPI score and bone marrow BM involvement. Thus, the initial CNS involvement might be associated with advanced stage of lymphoma not with ovarian involvement itself. Surgical removal of involved ovary was performed in 20 patients (62%), and then they were treated with systemic chemotherapy. Twelve patients (38%) were treated with chemotherapy alone. The comparison of outcomes according to the treatment modalities showed the outcomes of chemotherapy-based treatment versus surgery-based treatment were not significantly different (2 year overall survival; 66% vs. 68%). With a median follow-up of 25 months (range 3-185), 13 patients (40.6%) relapsed. Two patients were relapsed in single lesion and 11 were relapsed in multiple lesions. The majority relapsed at various extranodal sites (11/13, 84.6%) and only 2 cases relapsed at nodal sites. Most common relapse site was CNS (4 cases among 13 cases of relapse, 31%). All CNS relapsed patients had DLBCL histology. Ovarian relapse observed in one case that had been involved both ovary at the time of diagnosis. The 2 year overall survivals (OS) were 67% (95% CI: 50 to 83%) and the 2 year progression free survivals (PFS) were 61% (95% CI: 44 to 78%). In univariate analysis, high IPI score, 2 or more extranodal sites involvement and elevated LDH level were statistically significant parameters for lower PFS; moreover, 2 or more extranodal sites involvement and elevated LDH level associated with poor OS. Conclusion Ovarian involvement of non-Hodgkin's lymphoma showed a dismal prognosis despite active treatment. Therefore, more optimal treatment strategy should be warranted. Disclosures No relevant conflicts of interest to declare.

Outcome of Young Children with Non-Hodgkin's Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5106-5106
Author(s):  
Laura Rodriguez ◽  
Mohammed Zolaly ◽  
Sheila Weitzman ◽  
Ahmed Naqvi ◽  
Angela Punnet ◽  
...  
Keyword(s):  
Young Children ◽  
Hodgkin’S Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Organ Transplant ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Abstract 5106 Background: The incidence and biology of non-Hodgkin's lymphoma (NHL) vary according to age, and the outcome differs amongst children being less favorable in infants and adolescents. Objectives: To analyze the outcome and toxicity patterns of young children with NHL comparing patients aged < 10 years to those 10–18 years of age. Methods: A retrospective review of children ≤ 18 years of age diagnosed with NHL over a period of 13 years. Patients were treated according to different protocols and treatment subgroups included: Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), lymphoblastic lymphoma (LL), anaplastic large cell lymphoma (ALCL), and peripheral T-cell lymphoma (PTCL). Post-organ transplant lymphoproliferative disorder (PTLD) and immunodeficient patients were excluded. Results: From 01/1995 to 12/2008, 173 children with NHL were reviewed. Of these, 81 pts (47%) were <10 years of age, with BL (29 pts), DLBCL (5 pts), PTCL (6 pts), LL (27 pts), and ALCL (14 pts). The 10-year overall survival (OS) was 93. 6+2. 8% in patients aged < 10 years compared to 77. 3+7. 2 in patients 10–18 years of age (P=0. 02). The 10-year event-free survival (EFS) was 89. 4+3. 5% in patients aged < 10 years compared to 70+9. 3% in patients 10–18 years of age (P=0. 03). BL was the most common subtype in patients <10 years, with a 10-year EFS of 96. 4+3. 5% versus 82. 6+7. 9% in patients 10–18 years of age (P=0. 10). The most common subtype in patients 10–18 years of age was ALCL (36%), the 10-year EFS was 78. 5+8. 3 versus 92. 9+6. 9 in patients < 10 years (P=0. 29). Children 10–18 years of age were more likely to develop neurotoxicity (9. 7% vs 0%), gastrointestinal toxicity (30% vs 12%), and treatment-related mortality (4. 3% vs 2. 4%). Conclusions: Children < 10 years with NHL have better outcomes and less treatment-related toxicity than older children. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin's lymphoma: a British National Lymphoma Investigation Study

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 1046-1051 ◽  
Author(s):  
ME Hill ◽  
KA MacLennan ◽  
DC Cunningham ◽  
B Vaughan Hudson ◽  
M Burke ◽  
...  
Keyword(s):  
B Cell ◽  
Relapse Rate ◽  
Hodgkin’S Lymphoma ◽  
Prognostic Significance ◽  
Large Cell ◽  
Breakpoint Region ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Working Formulation

The Bcl-2 protein is capable of preventing apoptosis, and in vitro evidence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's lymphoma (NHL), but the clinical significance of these findings is controversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrangement in a large cohort of prospectively accrued patients with intermediate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in British National Lymphoma investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin blocks were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain reaction-based method, and for Bcl-2 expression using immunohistochemistry. Failure to achieve complete remission (CR), relapse, death from NHL, and deaths from all causes were used as end points to measure CR rate, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identified and tested for the bcl-2 MBR translocation, with 27 (17%) found to be positive; 153 of these patients were tested with immunocytochemistry, and 84 (55%) showed evidence of Bcl-2 expression. For patients who achieved CR from the initial treatment, the relapse rate was significantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the only factor significantly related to relapse rate in the subjects measured. The cause-specific survival for NHL in the series as a whole was significantly lower in patients with Bcl-2 expression than in those without. MBR status had no significant influence on any of the outcome measures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse.

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