Prognostic Significance of Cell of Origin Subclassification in Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5081-5081
Author(s):  
Muath Dawod ◽  
Juan Gomez-Gelvez ◽  
Ahmad Mattour ◽  
Kedar V. Inamdar ◽  
Nalini Janakiraman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Free Survival ◽  
Large B Cell Lymphoma

Abstract Abstract 5081 Background: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that has been divided into three different prognostic subgroups: Germinal Center B cell-like (GC), Activated B cell-like (ABC) and type 3 according to gene expression profile using cDNA. Immunohistochemistry (IHC) has been used as surrogate to identify these cell-of-origin subgroups. Data about the prognostic value of IHC has been conflicting. Patients and methods: In this retrospective study, we reviewed the charts of 252 patients diagnosed with DLBCL at Henry Ford Hospital from 1999 to 2012. We excluded patients with HIV, transformed lymphomas and unavailable samples. Data was collected on a total of 157 patients. The following data was gathered: age, sex, race, IPI score, disease stage, hemoglobin, white blood and platelet counts, best response achieved and dates of treatment start, relapse, death or last follow up. Tissue microarray slides with the following IHC stains (CD10, MUM1, Bcl6) were prepared and reviewed when needed. Using Hans Algorithm, samples were divided into two major groups (GC-like and non-GC-like). 3-year progression free and overall survivals were compared between all subgroups using a log-rank test. Continuous variables were reported as median and range, and compared using Wilcoxon rank-sum tests. Categorical variables were reported as median and range, and compared using Chi-square tests. Statistical significance was set at p<0. 05. Results: Eighty patients (51%) were classified as GC-like, and 77 patients (49%) as non-GC-like. GC-like subgroup had a significantly longer 3-year progression free survival (90% vs 74%, P=0. 024), as compared with the non-GC-like subgroup. There was a trend toward longer overall survival but it didn't reach statistical significance (74% vs 67%, P=0. 161). For all patients, IPI stands as a strong prognostic index with 3-year overall survival of (85% and 46%, P=<. 001) in patients with low IPI (0 to 2) and high IPI (3 to 5) respectively. Interestingly, in patients with low IPI, cell of origin stands as a prognostic factor with 3-year progression free survival of (96% and 81%, P=0. 032) in GC-like and non-GC-like groups respectively. While in patients with high IPI, there was no significant difference in progression free survival in cell-of-origin subgroups. Conclusion: Cell of origin subclassification as determined by IHC surrogate markers predict for better progression free survival in GC-like subgroup but not for overall survival. While this prognostic value was maintained in patients with low IPI, there was no prognostic significance in patients with high IPI. IPI is still a valuable prognostic tool in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

2020 ◽  
Author(s):  
Hsu-Chih Chien ◽  
Deborah Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Chunyang Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Electronic Health Record Data ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2817-2817 ◽  
Author(s):  
Kerry J. Savage ◽  
Mukesh Chhanabhai ◽  
Nicholas Voss ◽  
Shenkier Tamara ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07

Significance of c-myc Rearrangements in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2030-2030
Author(s):  
Philip Bierman ◽  
Fausto Loberiza ◽  
Bhavana Dave ◽  
Warren Sanger ◽  
R. Gregory Bociek ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Overall Survival Rates

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.

The Impact of Activated Akt Expression On Clinical Outcome in Diffuse Large B-Cell Lymphoma: A Clinicopathological Study of 99 Cases.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2676-2676
Author(s):  
Jung Yong Hong ◽  
Moon Ki Choi ◽  
Young Saing Kim ◽  
Chi Hoon Maeng ◽  
Su Jin Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Clinical Impact ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 2676 Purpose Akt is a serine/threonine kinase that plays a central role in cell proliferation and growth. To define clinical impact of Akt expression in diffuse large B-cell lymphoma(DLBCL), we investigated the expression of phospho-Akt(p-Akt) in DLBCL and analyzed clinical impact of p-Akt expression on patient survival. Methods We evaluated the p-Akt expression in 99 DLBCL patients using tissue microarray(TMA) technology. Results Positive p-Akt expression was observed in 15.2% of the patients and significantly associated with elevated lactic dehydrogenase level (P = .044). Kaplan-Meier survival analysis showed that the patients with positive p-Akt expression showed substantially poorer overall survival (p-Akt+ vs p-Akt- 25.3 months [95% confidence interval(CI), 14.4–36.2 months] vs 192.6 months [95% CI, 131.3–253.9 months], P < .001) and progression-free survival (p-Akt+ vs p-Akt- 13.6 months[95% CI, 14.4–36.2 months] vs 134.5 months [95% CI, 131.3–253.9 months], P < .001), respectively. Multivariate Cox regression analysis revealed that patients with DLBCL with p-Akt positivity showed poorer overall survival with 3.2 fold (95% CI, 1.6–6.8, P = .002) risk for death compared to patients with DLBCL with p-Akt negativity. Conclusion Positive expression of p-Akt in DLBCL patients is associated with poorer overall and progression-free survival. Expression of p-Akt may act as an independent poor prognostic factor and might be a novel therapeutic target for DLBCL. Disclosures: No relevant conflicts of interest to declare.

Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8040-8040 ◽  
Author(s):  
K. Fu ◽  
K. D. Perry ◽  
L. M. Smith ◽  
C. P. Hans ◽  
T. C. Greiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8040 Background: Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subgroups, i.e. germinal center B-cell (GCB) and activated B-cell (ABC) DLBCL, which were initially characterized by gene expression profiling and subsequently validated by immunostaining. Bcl-2 has also been identified as a prognostic indicator in the ABC subgroup. However, with the addition of rituximab (R) to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Methods: We studied 119 cases of de novo DLBCL including 70 cases treated with R-CHOP and 49 cases treated with CHOP. The cases were assigned to either the GCB or non-GCB subgroups using the methodology described by Hans et al (Blood 2004; 103:275). Characteristics of the patients were compared using the Chi-square test. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan Meier method and compared with the log-rank test. Results: The median age of the 119 patients was 67 years, ranging from 20 to 90 years, and there were 62 males and 57 females. The clinical characteristics of patients treated with CHOP versus R-CHOP, including the IPI, were comparable. R-CHOP was more effective than CHOP with improved 5-year EFS (63% vs 41%, p=0.013) and OS (78% vs 47%, p<0.001). In both patient groups treated with R-CHOP or CHOP, the GCB subgroup had a significantly better 5-year EFS and OS compared to the non-GCB subgroup (OS: 91% vs 64% for R-CHOP, p=0.0073; 67% vs 31% for CHOP, p=0.034, respectively). Additionally, both the GCB and non-GCB subgroups treated with R-CHOP had a significantly improved OS compared to their respective subgroups receiving CHOP alone (GCB, p=0.015; non-GCB, p=0.019). Bcl-2 expression was not a significant predictor in either the GCB or non-GCB subgroups treated with R-CHOP (OS, GCB: p=0.32; non-GCB: p=0.43). Conclusions: In this retrospective study, we demonstrate that subclassification based on the cell of origin continues to have prognostic significance in patients with DLBCL treated with R-CHOP. Addition of rituximab to CHOP improves the overall survival of patients with DLBCL in both the GCB and non-GCB subgroups. No significant financial relationships to disclose.

FCgammaRIIa Polymorphism Is Not Associated with Overall Response, Progression Free Survival and Overall Survival In Diffuse Large B-Cell Lymphoma Treated with Rituximab

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5078-5078
Author(s):  
Marcelo Bellesso ◽  
Sergio Paulo Bydlowski ◽  
Renata Oliveira Costa ◽  
Felipe Vieira Rodrigues Maciel ◽  
Debora Levy ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Free Survival ◽  
Overall Response ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 5078 Background: Low-affinity receptor for the Fcγ region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab′)2 Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP). Methods: Here we analyzed the role of specific polymorphism of activating FcγRIIA in 64 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR), Progression Free Survival (PFS) and Overall Survival (OS) using a polymerase chain reaction-restriction fragment length polymorphism method. Results: The median age of the patients was 48.6 years. Out of the 64 patients (32%), were stage III-IV and 27 (42.5%) had more than 2 factors of the International Prognostic Index. Fity-six (89%) had CR and 7 (9.5%) had refractory disease (RD). Seven (11%) of the patients presented relapses. Deaths occurred in 6 (9.3%) patients with follow up of 19,5 months (range 21,3-50,1). The distribution of FcγRIIA polymorphism genotypes was: 15 (23,4%) HH, 30(46,9%) HR and 19(29,7%) RR, while considering only two groups (HH and R allele (HR and RR) was 15 (23,4%) and 49 (76,6%). There were no statistically significant differences in the genotypes groups according prognostic factors. In addition, there were not differences between response rate and FcγRIIA genotypes polymorphism: the CR in HH and HR/ RR were respectively 80% and 89%, p=0,377. It was not found differences regarding FcγRIIa. HH genotype presented a median PFS and OS. Thus, PFS HH genotype presented a median PFS 20,96 ± 10,49 months versus HR/RR median PFS 12,03 ± 7,71 months, p = 0,765, and OS 23,26 ± 10,42 months versus HR/ RR median OS 12,7 ± 7,42 months, p =0,98. Conclusions: Contrary to recent report we showed that FcγRIIA polymorphism is not associated to overall response, PFS and OS in patients with DLBCL treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Is Interim/Mid-Treatment PET (interim PET, i-PET) Scan Predictive of Outcome in Diffuse Large B-Cell Lymphoma?.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2675-2675
Author(s):  
Dushyant Verma ◽  
Amol Takalkar ◽  
Runhua Shi ◽  
Glenn M. Mills ◽  
Srikanth Paladugu ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Free Survival ◽  
Interim Pet ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2675 Background: Initial treatment of diffuse large B-cell lymphoma (DLBCL) involves 6–8 cycles of chemo-immunotherapy and may be curative in 60–65% of patients. However, in the remaining patients, subsequent therapies appear inadequate for long lasting remission. A strategy to improve patient outcomes could involve early identification of patients who do not respond to treatment as expected and then employing different/aggressive treatment modalities in these patients. PET scan done during mid-treatment (interim PET, i-PET) may help identify these patients early. However, the value of i-PET in DLBCL is not established as there is controversy about its prognostic value and studies are ongoing to evaluate its benefit. Aims: To determine predictive value of i-PET on progression-free survival (PFS), overall survival (OS) in DLBCL patients. Methods: We performed retrospective analysis of DLBCL patients treated at LSU Health Shreveport, LA, between Jan 2002 – July 2012. All patients were treated with R-CHOP chemotherapy. PET-CT was performed at baseline at time of diagnosis, after 2 to 4 courses (i-PET) and at the end of therapy (final PET, f-PET). Results: Forty-four patients were evaluable for analysis. The median age was 55 years (range 21–84), 32 (73%) were males. Ann-arbor staging showed 5 patients each in stage I and II, 11 patients in stage III, 23 in stage IV, and the median IPI score was 3. Median time to i-PET was after 3 cycles of chemotherapy, and median days to i-PET after chemotherapy were 16. The median follow-up duration from start of chemotherapy was 23 months (range 4 – 89). The PET results were as follows: i-PET negative 30 (68%), i-PET positive 14 (32%) patients. Final PET results were: f-PET negative 33 (75%), f-PET positive 11 (25%) patients. The 3-year PFS was 96.3% and 35.7% for i-PET negative versus positive patients respectively (p<0.001), and the 3-year PFS for f-PET negative versus positive patients was 78.9%% versus 30.0% respectively (p<0.001). The 3-year OS was 79.4% and 62.6% for i-PET negative versus positive patients respectively (p=0.3306). The 3-year OS was 79.9% and 58.7% for f-PET negative versus positive patients respectively (p=0.021). Conclusion: Interim/mid-treatment PET (i-PET) scan is predictive of progression free survival but not overall survival for DLBCL patients. A final PET (f-PET) scan is predictive of progression free survival as well as overall survival for DLBCL patients. Larger prospective studies are needed to confirm these findings and could also look into the biology of i-PET positive patients by gene expressing profiling (GEP) and evaluate the role of novel agents in modifying the disease course. Disclosures: No relevant conflicts of interest to declare.

Additional Two Cycles of Rituximab Improves the Prognosis of Low-Risk NCCN-IPI Diffuse Large B-Cell Lymphoma Patients Responded to R-CHOP Regimen

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2733-2733
Author(s):  
Pengpeng Xu ◽  
Huijuan Zhong ◽  
Weili Zhao
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Chop Regimen ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas with a relapse/refractory rate of 30-40% under the current standard Rituximab plus cyclophophamide, adrimycin, vincristine and prednisone (R-CHOP21) treatment. As mechanism of action, Rituximab can target the B-cell receptor (BCR) and NF-ĸB signaling pathways, of which activating gene mutations are most frequently identified in activated B-cell-like (ABC) subtype of DLBCL and associated with increased disease relapse of the patients. The aim of our study was to investigate the clinical efficacy of additional two cycles of Rituximab maintenance (RM) in DLBCL and its relation with mutational status involved in BCR/NF-ĸB cascade. Methods: We retrospectively analyzed a total of 534 de novo DLBCL patients after 6 cycles of R-CHOP21 regimen in our institution from December 1998 to December 2012. Among 413 patients achieved complete response (CR), 211 patients received additional 2 cycles of RM in a intent-to-treat manner and 202 patients underwent observation (OBS). The remaining 121 patients were primarly refractory to R-CHOP regimen. All the patients were classified according to IPI and NCCN-IPI as previously described. Immunohistochemistry for germinal center B-cell (GCB) or non-GCB subgroups were determined by Hans classification. The mutational status of BCR/NF-ĸB-associated genes (mainly as CD79A, CD79B, MYD88, and CARD11) were detected in tumor samples of 124 patients (48 cases, 43 cases and 33 cases in the RM, OBS and Refractory group, respectively). Results: No significant difference of clincial and biological characteristics were found between the RM and OBS group, including age, gender, Ann Arbor stage, ECOG score, number of extranodal involvements, serum lactic dehydrogenase level, B symptoms, IPI and NCCN-IPI risk group, and GCB/non-GCB ratio. With a median follow-up of 36.5 months, the 3-year progrssion free survival (PFS) was 79.9% and 73.6% (P=0.123), and the 3-year overall survival (OS) was 91.0% and 87.4% (P=0.149) in RM and OBS group, respectively. According to NCCN-IPI, remarkable improvement of 3-year PFS and OS was observed in low-risk patients of the RM group (100% and 100%), comparing with those of the OBS group (82.5% and 88.2%, P=0.003 and 0.027 respectively, Figure 1). Similarly, male patients with low-risk IPI could also benefit from additional 2 cycles of Rituximab with a 3-year PFS of 100% in RM vs 84.4% in OBS (P=0.006). Overall, BCR/NF-ĸB mutations were detected in 46/124 patients (37.1%), including 20/48 (41.7%), 13/43(30.2%) and 13/33 (39.4%) patients in RM, OBS and Refractory group, respectively. However, MYD88 mutations were more frequently observed in the Refractory group than in the RM/OBS group (18/33 vs 6/91, P<0.001, Table 1). Mutations are not prognostic indicators for PFS or OS in general, but interestingly, those mutation-bearing patients showed a tendency of improved disease prognosis in the RM group compared with that of the OBS group (3-year PFS 85.5% vs 70.0%, P=0.091, 3-year OS 94.7% vs 71.6%, P=0.059, Figure 2). Conclusion: Low-risk NCCI-IPI patients with DLBCL responded to R-CHOP regimen benefit from additional two cycles of RM. As a potential target of Rituximab, BCR/NF-ĸB-associated mutations reflected disease resistance to Rituximab. Whether prolonged administration of Rituximab could improve the prognosis of the patients with these mutations warrants further investigation. Table 1. The distribution of BCR/NF-κB-associated mutations in patients with DLBCL Mutated gene Refractory (N=33) CR (N=91) Additional 2R (N=48) Observation (N=43) P value CD79a 1 (3.0%) 0 (0%) 0 (0%) 0.595a CD79b 5 (15.1%) 10 (20.8%) 6 (13.9%) 0.750 a MYD88 18 (54.5%) 3 (6.0%) 3 (6.9%) <0.001b CARD11 1 (3.0%) 7 (14.0%) 4 (9.3%) 0.244a a: No significantly difference was found between Refractory group and CR group. b: Significantly difference was found between Refractory group and CR group (p<0.05). Figure 1. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients according to low-risk NCCN-IPI. Figure 1. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients according to low-risk NCCN-IPI. Figure 2. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients with BCR/NF-ĸB-associated mutations. Figure 2. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients with BCR/NF-ĸB-associated mutations. Disclosures No relevant conflicts of interest to declare.

BCL6 Rearrangement Detected by FISH Analysis Is a Poor Prognostic Factor in the “Non-Germinal Center Phenotype” of Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4620-4620
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Akihito Momoi ◽  
Toshiki Kitajima ◽  
Masutaka Higashimura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL), which is the most common type of adult non-Hodgkin lymphoma, is considered to be heterogeneous in cytogenetics, immunophenotype and clinical feature. As the results of gene expression profiling, DLBCL can be divided into prognostically significant 3 subgroups of germinal center B-like (GCB), activated B-like and type 3. Chromosomal translocations affecting the BCL6 locus at the 3q27 locus are common in DLBCL, however, the prognostic significance of BCL6 rearrangement is still controversial. Methods: Twenty-six cases of DLBCL were examined with interphase fluorescence in situ hybridization (FISH) on touch preparations of lymph nodes using LSI BCL6 dual color probes (Vysis) for the incidence of BCL6 rearrangement and immunohistochemistry on paraffin section using CD10, BCL6 and MUM1 for subclassfying “GCB phenotype” and “non-GCB phenotype”. The correlation of BCL6 rearrangement with survival was investigated in two subgroups of DLBCL. Results: Of the 26 DLBCL cases, 6 cases (23%) were considered GCB phenotype and 20 cases (77%) non-GCB phenotype. BCL6 rearrangements were detected in 2 of 6 cases (33%) with GCB phenotype and 9 of 20 (45%) with non-GCB phenotype (total 11/26, 42%). ALL 6 cases with the GCB phenotype achieved sustained complete remission after chemotherapy and are alive. On the other hand, complete remission rate was 22% for the cases with BCL6 rearrangement but 73% for the cases without BCL6 rearrangement in the non-GCB phenotype (p=0.069). BCL6 rearrangement had a significant adverse effect on progression free survival within the non-GCB phenotype (P=0.016), but there was no significant correlation between BCL6 rearrangement and overall survival. Conclusion: FISH-based technique of the BCL6 rearrangements using touch preparations of lymph nodes could be developed for the retrospective analysis on survival. BCL6 rearrangement showed a poor prognostic effect particular in the non-GCB subgroup of DLBCL. Overall survival Overall survival Progression free survival Progression free survival

Rituximab Improves Overall Survival In Patients Treated With CODOX-M/IVAC For Burkitt Lymphoma (BL) and B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and BL: A Single Center Experience and Review Of The Literature

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5093-5093
Author(s):  
Anca Prica ◽  
Ariella Pratzer ◽  
Matthew C Cheung ◽  
Kim Thompson ◽  
Eugenia Piliotis ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Median Time ◽  
Burkitt Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background Dose-modified(dm) CODOX-M/IVAC is commonly used for Burkitt lymphoma (BL) and overlap aggressive B cell lymphomas (B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL, previously Burkitt-like lymphoma-BLL), with high cure rates, but significant toxicity. The concurrent use of rituximab with CODOX-M/IVAC is relatively new in both BL and BLL. Methods: We undertook this retrospective study of BL and BLL patients treated at a large quaternary care cancer center with dmCODOX-M/IVAC +/-rituximab(R) in order to a) determine ‘real-world' toxicity and survival rates, b) examine the effects of BL versus intermediate histology diagnoses, and c) evaluate the effects of rituximab (R) use. Patients diagnosed between January 2006-December 2012 as having either Burkitt lymphoma or atypical Burkitt/Burkitt-like lymphoma (WHO Classification 2001), or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and BL (WHO 2008) and who had received the dmCODOX-M/IVAC regimen,+/- R within 2 months of their diagnosis, were identified.  In May 2008, we adopted the practice of adding R 375 mg/m2 to dmCODOX-M/IVAC in non-HIV patients due to emerging data from other centers. In 2012, our approach to BLL was altered, by adding 1-4 cycles of R-CHOP after the dmCODOX-M/IVAC protocol completion, to maximize anthracycline and rituximab delivery. The primary outcomes of interest were 2-year overall (OS) and progression-free survival (PFS). Univariate and multivariable Cox proportional hazard models of OS and PFS were constructed.   Results: 31 patients with BL (n=21) or BLL (n=10) were included.  The median age was 45, and 90% were high risk. 94% of patients displayed a MYC translocation (t(8;14)) by FISH cytogenetics. Additionally, 8 (26%) patients were BCL2+ by immunohistochemistry (IHC). Three were also positive for the t(14;18) (double-hit lymphomas), and one was unknown.  Because of the diagnostic uncertainty (pending MYC status), 10 (32%) began treatment with chemotherapy other than dmCODOX-M/IVAC (mostly 1-2 cycles of CHOP+/-R). The median time from diagnosis to first chemotherapy was 13 days (1-58) and from first chemo to first HDMTX 10.5 days (0-57).  In total, 22 (71%) patients received at least one infusion of rituximab at some point during first line treatment with a median of 3 infusions (range 1-7). Five of 10 BLL patients (50%) received a median of 2 additional R-CHOP cycles (range 1-4). In the patients who received R-CHOP first vs. those who did not, the median time from diagnosis to the first chemotherapy was 9 days (range: 1-21) compared with 17 days (range: 0-58) (p=0.29).  Despite GCSF use, 24 patients (77%) experienced at least one episode of febrile neutropenia post dmCODOX-M and 12 patients (39%) post dmIVAC. The 2-year overall survival (OS) and progression-free survival (PFS) were 69% and 62%, respectively, with no differences between BL and BLL (Figure 1).  When BLL was separated by whether R-CHOP was given, there were still no differences in OS between BL, BLL (“no R-CHOP after”) and BLL (“R-CHOP after”) (2-yr OS 64% vs. 60% vs. 100%, p=0.38; Figure 1). Patients who received rituximab had superior OS (2-yr OS 86% vs. 33%, p=0.0013; Figure 1) compared with those that did not.  Starting with CHOP-R versus dmCODOX-M was associated with an OS benefit (2-yr OS 100% vs. 53%, p=0.009; Figure 1), despite no difference in OS whether time from diagnosis to first chemotherapy was ≥ or < 10 days (p=0.96) By multivariable analysis, rituximab use was significantly associated with improved OS (HR 0.15; 95%CI 0.04-0.56) and PFS (HR 0.05; 95%CI 0.01-0.32). Conclusion The addition of rituximab to dmCODOX-M/IVAC improves overall and progression free survival in both BL and BLL and is recommended.  BLL is a challenging histology to treat with inferior outcomes to DLBCL when treated similarly. The use of an aggressive regimen such as R-dmCODOX-M/IVAC in BLL can yield promising results that are comparable to BL. Disclosures: No relevant conflicts of interest to declare.

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