Double and Triple Hit Diffuse Large B Cell Lymphomas and First Line Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4885-4885
Author(s):  
Michael V. Jaglal ◽  
Deniz Peker ◽  
Jianguo Tao ◽  
Jennifer L. Cultrera
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Treatment Regimen ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Cns Disease ◽  
Entire Cohort ◽  
First Line Therapy ◽  
Genetic Abnormalities

Abstract Abstract 4885 Background: B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL) or Burkitt like lymphoma is a high grade lymphoma, with a high proliferation index and a complex karyotype mostly involving MYC and BCL-2 genes, so called “double hit” as well as BCL-6 genes, so called “triple hit”. This high grade lymphoma shows an aggressive behavior for which the most appropriate therapeutic approach is not established. Methods: This was a single center retrospective review of patients with a confirmed diagnosis of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL from 2006 to 2012. The definitive diagnosis in all cases was based on morphological and phenotypic features, and genetic abnormalities involving MYC, BCL-2, and BCL-6. Clinicopathological data was extracted including age, gender, primary disease location, phenotypic subtype, genetic abnormalities by FISH, IPI scores, treatment regimens and survival data. Descriptive statistical analyses were utilized. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data were analyzed using SPSS version 19.0 statistical software. Results: 31 patients with “Double or Triple Hit” lymphomas were identified between 2006 and 2012. The age range at diagnosis was 33–87 years with median age of 71. 23 of 31 patients (74 %) were ≥ 60 years old. Male to female ratio was 1.58:1 (19:12). The median ECOG PS was 1. No patients had HIV. A majority of patients presented with extranodal disease 21 out of 31 patients and only 10 patients presented with nodal disease. The mean overall survival of the entire cohort was 28 months with ranges 3 to 40 months. 20 of 31 patients (65%) are currently alive. RCHOP was the most utilized treatment regimen in the cohort of alive patients 13 out of 20 patients (65%). Patients who presented with CNS disease had a worse prognosis when compared to the entire cohort with a mean overall survival of 13 months versus non CNS disease overall survival was 32 months (p=0.014). In patients treated with RCHOP for first line therapy the overall survival was 33 months versus 17 months for non RCHOP regimens first line (p=.048). The non RCHOP regimens included Hyper CVAD, ESHAP, and RICE. Conclusions: RCHOP was the most utilized treatment regimen in the cohort of alive patients. The treatment regimen with the best efficacy in this retrospective study was RCHOP in first line treatment of “Double or Triple Hit” lymphomas. CNS disease is associated with worse prognosis in patients with “Double or Triple Hit” lymphomas in this retrospective study. Disclosures: No relevant conflicts of interest to declare.

A review of clinicopathologic characteristics, therapy, and outcomes of 22 patients with aggressive B-cell lymphoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21123-e21123
Author(s):  
Michael Jaglal ◽  
Deniz Peker ◽  
Celeste M. Bello ◽  
Bijal D. Shah ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Proliferation Index ◽  
High Grade ◽  
Female Ratio ◽  
Cns Disease ◽  
Entire Cohort ◽  
Genetic Abnormalities ◽  
Worse Prognosis

e21123 Background: B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL) or Burkitt like lymphoma is a high grade lymphoma that is associated with a high proliferation index and a complex karyotype mostly involving MYC and BCL-2 genes, so called “double hit” as well as BCL-6 or CYCLIND1 genes, so called “triple hit”. This high grade lymphoma shows an aggressive behavior for which the most appropriate therapeutic approach is yet to be established. Methods: This was a single center retrospective review of pts with a confirmed diagnosis of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL from 2006 to 2011. The definitive diagnosis in all cases was based on morphological and phenotypic features, and genetic abnormalities involving MYC, BCL-2, BCL-6, and or CYCLIND1. Clinicopathological data was extracted including age, gender, primary disease location, phenotypic subtype, genetic abnormalities by FISH, IPI scores, treatment regimens and survival data . Descriptive statistical analyses were utilized. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data were analyzed using SPSS version 20.0 statistical software. Results: 22 pts with "Double or Triple Hit" lymphomas were identified between 2006 and 2011. The age range at diagnosis was 33-87 years with median age of 66. 16 of 22 pts (73%) were ≥ 60 years old. Male to female ratio was 1.75 :1 (14:8). The median ECOG PS was 1. No pts had HIV. A majority of pts presented with extranodal disease 17 with only 5 pts presenting with nodal disease. The median survival of the entire cohort was 9 months with ranges 32 to 2 months. 16 of 22 pts (73%) are currently alive. In the cohort of pts that are currently alive, 10 was treated with RCHOP and 6 with RHyperCVAD. Pts who presented with CNS disease had a worse prognosis when compared to the entire cohort with a median overall survival of 6.5 months (p=0.016). Conclusions: RCHOP was the most utilized treatment regimen in the cohort of  alive patients. CNS disease is associated with worse prognosis in patients with "Double or Triple Hit" lymphomas.

Poor Outcomes Among Patients Failing Dose-Adjusted EPOCH in Aggressive Lymphoma: A Collaborative, Retrospective Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1518-1518 ◽  
Author(s):  
Jackie Vandermeer ◽  
Allison M Winter ◽  
Ajay K. Gopal ◽  
Ryan D. Cassaday ◽  
Brian T. Hill ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Salvage Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy

Abstract Introduction Among patients with aggressive B-NHL who fail RCHOP, about half respond to standard salvage regimens and may proceed to curative-intent, transplant-based therapy. However, whether pts failing more intensive regimens such as dose-adjusted, infusional EPOCH benefit from standard salvage regimens is unclear. We hypothesized that such patients comprise a higher-risk cohort, facing inferior response rates and outcomes using standard salvage regimens. We undertook a collaborative study to assess response rates and survival among pts failing EPOCH for aggressive B-NHL, to inform patient management and design of clinical trials in this setting. Methods Pharmacy records and institutional databases were queried, identifying pts receiving EPOCH over the last 10 years at the University of Washington/SCCA and the Cleveland Clinic Foundation, for combined analysis. Under IRB approval, patient characteristics, histology, outcome with EPOCH, time to EPOCH failure, response to salvage, and overall survival were analyzed. Diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, B-cell-lymphoma unclassifiable, HIV-associated B cell lymphoma, and transformed B cell non-Hodgkin lymphoma were included. Pts receiving <2 cycles EPOCH, or who had inadequate follow-up (<3 months), were excluded. Failure of EPOCH was defined as failure to respond or progression during therapy, need for initiation of salvage therapy, or death during therapy of any cause. Adverse events or treatment change due to toxicity were not included in the definition of failure. JMP 11 was used to generate kaplan-meier survival estimates. Results 124 pts with aggressive B-NHL receiving EPOCH were identified. 54 had not relapsed, and among 70 remaining da-EPOCH failures, 37 met the above inclusion criteria. Median age was 55. 27% were female, and 23 received EPOCH as first-line therapy. All but 3 received rituximab with EPOCH. Histologies were primarily DLBCL in 22/37 (60%) and BCL-U in 12/37 (32%) carrying a MYC translocation; most of these harbored additional translocations in BCL2 and/or BCL6 (10/12). However, data regarding MYC rearrangement was not available for all pts. 2 had HIV-associated B-NHL and 3 had PMBCL. With 18 months follow up, the median time to EPOCH failure was 5 months. Only 3 EPOCH failures occurred late (>12 months). Median OS from the date of EPOCH failure was 10 months (Figure 1). Those receiving EPOCH as first-line therapy (23) had a median OS of 14 months from EPOCH failure, as opposed to 4 months for those receiving EPOCH as salvage therapy (log-rank p=.01). Salvage chemotherapy regimens after EPOCH were diverse, and generally ineffective; 6/28 (21%) regimens produced a response (Table 1). Among patients failing EPOCH within a year, platinum-containing salvage (RICE/RDHAP) was effective in only 2/13 patients (15%). 9 patients did not receive any salvage, most of whom died or proceeded to palliative measures and/or hospice care. Conclusions A relatively low overall response rate (21%) was observed in this retrospective analysis of patients failing EPOCH. Analogous to early RCHOP failure in the CORAL study, those failing EPOCH within a year may face inferior outcomes with platinum-based salvage therapy. While combined from two institutions, our data represent a modest sample size and require confirmation. If verified, examination of mechanisms of resistance to EPOCH, and selecting EPOCH failures for clinical trials of novel targeted therapies and transplant-based approaches, may prove critical. Table 1. Salvage Therapy for REPOCH failures Regimen: response/total number treated Notes Response to any salvage: 6/28 (21%) Some patients received more than 1 chemo salvage; responses were tabulated per regimen. RICE: 4/12 2/3 alive post transplant(1 auto 1 allo; 1 declined transplant and survived; 1 died) RDHAP: 1/6 Gemcitabine-based: 0/5 HyperCVAD (Part A and/or B): 1/5 Survivor had CNS only relapse, received regimen B and transplant 9- received no systemic treatmen; most died or proceeded to palliative measures and/or hospice Figure 1. Figure 1. Disclosures Gopal: Gilead: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Emergent/Abbott: Research Funding; Sanofi-Aventis: Honoraria; Seattle Genetics: Consultancy, Honoraria; BioMarin: Research Funding; Piramal: Research Funding; Janssen: Consultancy; Millenium: Honoraria, Research Funding; BMS: Research Funding; Merck: Research Funding. Hill:Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Till:Roche/Genentech: Research Funding; Pfizer: Research Funding.

scholarly journals Clinical Characteristics and Treatment Outcomes in Patients Diagnosed with Primary Mediastinal Large B-Cell Lymphoma at Princess Margaret Cancer Centre from 1994-2012

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4447-4447
Author(s):  
Anna M. Dyszkiewicz-Korpanty ◽  
Manjula Maganti ◽  
David C. Hodgson ◽  
John G. Kuruvilla ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Current Therapy ◽  
Second Line ◽  
First Line ◽  
Cancer Centre ◽  
Line Chemotherapy

Abstract Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare clinical entity representing less than 2-4% of Non-Hodgkin lymphomas. PMBCL typically occurs in young adults, more often in females, with early stage disease usually limited to the antero-superior mediastinum. PMBCL tends to have a more locally aggressive clinical course with a substantial percentage of patients with primary refractory disease or early relapse. Patients with primary refractory or relapsed disease have a lower probability response to second-line therapy and proceeding to autologous stem cell transplant (ASCT). The optimum chemotherapy regimen and role of radiation are currently the subject of debate; for this reason we evaluated our experience using a uniform treatment policy of combined modality therapy (CMT), including factors that influence patient outcomes. Methods: We analysed 88 patients (median age 35, range 15-64) diagnosed with PMBCL, treated at Princess Margaret Cancer Centre from 1994-2012. Data on stage, clinical prognostic factors, pathologic characteristics (including presence of sclerosis) treatment and outcome were retrieved from a prospective lymphoma database and pathology reports. Statistical analysis was performed to assess the overall survival (OS) and progression free survival (PFS) at 5 years; PFS events were progressive disease (PD), relapse or death from any cause. Patient characteristics are shown in Table 1 Results: All patients received treatment with curative intent. In the majority of patients first-line chemotherapy was cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP, 47 patients) or CHOP + rituximab (R-CHOP, 38 patients) (average number of cycles = 6); standard involved field consolidative radiation was given to 68/83 patients (82%), with a median dose of 35 Gy, usually in 20 fractions. Following the first line treatment, 38 patients achieved CR (complete response), 33 patients had PR (partial response), PD occurred in 18 patients, 10 patients with initial response relapsed. 28/88 patients with PD or relapse received second line chemotherapy (cisplatin-based or Mini-BEAM) and 6/28 went on to ASCT. Twenty one of 88 (24 %) patients died from progressive lymphoma, 2/88 died of other causes. Overall survival (OS) at five years was 72.4%, and five year PFS in was 67.7%. We observed significantly inferior five year-OS and PFS in men by univariate analysis (p=0.019; OS= 51.9% vs 80.2% in women and p=0.022; PFS= 47.6 % vs 75.2% in women, respectively); The presence of sclerosis on tumor biopsy also resulted in inferior OS and PFS (OS= 60.4% vs 89.3 %, p=0.0045; PFS= 56.1% vs 81.7%, p=0.013, respectively);PFS and OS in patients treated with R-CHOP was superior to patients who received chemotherapy without Rituximab( PFS of 84.2% vs 55.8%, p= 0.0099 and OS of 89.2% vs 61.9%, p= 0.012). In multivariate analysis, male gender and tumor pathology (PMBCL with sclerosis) were predictive of inferior OS (p=0.018 and p= 0.022, respectively) and also, inferior PFS (p= 0.0499 and p= 0.024, respectively); age at diagnosis, stage and bulk did not have independent impact on OS or PFS. Conclusions: Current therapy with R-CHOP and radiation result in excellent PFS and OS. The reasons for adverse outcomes in males in our cohort and pathological correlates of extensive sclerosis are being explored. Table 1. Patient characteristics at presentation (n=88) Variable N (%) Females 62(70.4) Stage I 39(44.3) Stage II 42(47.7) Stage III-IV 8(9.1) B symptoms 27(30.7) Elevated LDH 44(50) Bulk > 10 cm 60 (68.2) Extranodal disease 37 (42) Disclosures Kukreti: Celgene: Honoraria. Porwit:Beckman-Coulter: Speakers Bureau.

The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial diffuse large B-cell lymphoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8566-8566
Author(s):  
Niels Murawski ◽  
Samira Zeynalova ◽  
Gerhard Held ◽  
Marita Ziepert ◽  
Barbara Kempf ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Multivariable Analysis ◽  
Cumulative Risk ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Cns Disease ◽  
Increased Risk

8566 Background: The role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement of aggressive B-cell lymphoma remains to be determined in the rituximab era. Methods: In a retrospective subgroup analysis of 9 consecutive prospective DSHNHL trials covering all DLBCL risk groups from 18 to 60 years of age, patients with and without craniofacial involvement were compared with respect to clinical presentation, event-free and overall survival. Results: 336 sites of extralymphatic craniofacial involvement were observed in 284/3840 (7.4%) patients (orbita: 30, paranasal sinuses: 90; main nasal cavity: 38, tongue: 26, remaining oral cavity: 99, salivary glands: 53). In a multivariable analysis adjusting for IPI risk factors the addition of rituximab improved EFS and OS in both patients with and without craniofacial involvement. The 141 responding patients who received radiotherapy to sites of craniofacial involvement had a similar 3-year event-free (79% vs 79%; p=0.835) and 3-year overall survival (88% vs. 85%; p=0.311) when compared with the 56 patients who did not receive radiotherapy. Without rituximab, the 2-year-rate of cumulative risk of CNS disease was increased in 205 patients with compared to 2586 patients without craniofacial involvement (4.2% vs. 2.8%; p=0.038), while this difference disappeared in patients who received CHOP(like) chemotherapy in combination with rituximab (1.7% in 77 patients with compared to 2.9% in 946 patients without craniofacial involvement; p=0.868). Of 85 patients with craniofacial involvement who received intrathecal prophylaxis with methotrexate, the 2-year-rate of cumulative risk of CNS disease was 4.3% compared to 2.3% in 189 patients who did not (p=0.995). Conclusions: Rituximab eliminates the increased risk for CNS disease in patients with craniofacial involvement. As a practical consequence intrathecal prophylaxis and radiotherapy to sites of craniofacial involvement should not be given any more.

Lymphoma Patients Secondary to Congenital and Acquired Immunodeficiency Syndroms in a Turkish Pediatric Oncology Center

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5445-5445
Author(s):  
Nurdan Tacyildiz ◽  
Gulsah Tanyildiz ◽  
Gulsan Yavuz ◽  
Emel Unal ◽  
Handan Dincaslan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Lymphoproliferative Syndrome

Abstract PURPOSE An increased incidence of lymphoma is seen in various types of immune deficiency syndromes,including congenital immune deficiency diseases, organ transplantation with iatrogenic immunosuppression and autoimmune disorders. Prognosis of the lymphomas secondary to immunodeficiencies is stil poor. We aimed to analyse clinical features and treatment results of our patients that diagnosed as lymphoma and have immundeficiency syndrom. PATIENTS Between 2002-2014, we have seen 12 (7male, 5 female) childhood lymphoma that related immunodeficiencies. Ages of patients were between 4-15 years (median 8 years).The follow up period is 1-140 months (median: 38.5 months) and survival rate is %58. Five of patients died because of the progressive disease. The characteristics of patients are summarized in the table. TABLE- Clinical characteristics of patients Patient Age (year) Gender Diagnosis Follow up (months) Survival 1. G.C 10 Male T-NHL + AT 6 Alive (lost to follow up) 2. İ.D 4 Male T-NHL + ALPS 9 Eksitus 3. M.K 12 Female T cell rich B cell lymphoma+ CVID 2 Eksitus 4. S.K 9 Female B cell lymphoblastic lymphoma+AT 54 Alive 5. B.C 5 Male BL + Renal transplantation 1 Eksitus 6. S.K 7 Female BL + AT 6 Eksitus 7. C.G 12 Male BL + WAS 48 Eksitus 8. K.B 11 Female BL+EBV associated lymphoproliferative syndrome 29 Alive 9. M.Y 15 Female HL + CVID 140 Alive 10. B.Ç 4 Male HL + selective IgA deficiency 132 Alive 11. S.S 7 Male HL + AT 70 Alive 12. B.K 5 Male HL + AT 48 Alive TOTAL n = 12 4-15 years Median : 8 4 female 8 male 8 NHL (survival % 37.5) 4 HL (survival% 100) 1-140 months Median : 38.5 Survival %58 RESULTS Two of 5 Ataxia Telangiectasia (AT) patients diagnosed as Hodgkin's lymphoma (HL) while other three diagnosed as non-Hodgkin's lymphoma (NHL) (1 Burkitt's lymphoma-BL,1 B cell lymphoblastic lymphoma-BCLL,1 T-cell NHL). One of 2 common variable immunodeficiency (CVID) patient diagnosed as HL and the other one diagnosed T-cell rich B-cell lymphoma (TCRBCL). Wiscott-Aldrich syndome (WAS), autoimmune lymphoproliferative syndrome (ALPS ) and selective immunoglobulin A deficiency patients diagnosed as large B-cell lymphoma (LBCL), T-cell NHL and HL, respectively. In one patient, EBV associated BL developed secondary to renal transplantation. Another EBV associated BL patient has been diagnosed recently who has DNA instability defect. Follow-up period of patients were between 1-140 months (median 38.5 months). Almost half of the patients ( 42%) were diagnosed as BL,BCLL or TCRBCL. Although, survival of our patients for median 38.5 months is 58% (5 patients died with progressive disease) ,four of the 5 BL&TCRBCL patients have been died. Two patients who are living after BL and BCLL diagnosis in that group are treated with Rituximab as first line therapy. CONCLUSİON BL is most common lymphoma type in immundeficient lymphoma patients which may be subject for future research . Although special attention has been given to these patients, especially survival of BL lymphoma secondary to immunodeficiencies are poor. Special treatment modalities, like targeted terapies may be necessary as first line therapy to improve survival of these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of infectious episodes occurring during first‐line therapy for diffuse large B‐cell lymphoma ‐ A nationwide cohort study

2020 ◽  
Vol 38 (3) ◽  
pp. 318-325
Author(s):  
Michael R. Clausen ◽  
Sinna P. Ulrichsen ◽  
Maja B. Juul ◽  
Christian B. Poulsen ◽  
Brian Iversen ◽  
...  
Keyword(s):  
Cohort Study ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Large B Cell
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