Rituximab Plus Dose Intense Rapid-Cycling Chemotherapy with Intrathecal CNS Prophylaxis in Patients with Burkitt Lymphoma (BL) and Intermediate Unclassifiable Diffuse Large B-Cell Lymphoma/BL: Single Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1631-1631
Author(s):  
Chiara Frairia ◽  
Chiara Ciochetto ◽  
Ernesta Audisio ◽  
Giulia Benevolo ◽  
Barbara Botto ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Rapid Cycling ◽  
High Dose Cytarabine ◽  
Group 2 ◽  
Group 1

Abstract Abstract 1631 Introduction. Burkitt Lymphoma (BL) and the novel category of B-cell lymphoma, unclassifiable, with features intermediate between BL and diffuse large B-cell lymphoma (intermediate DLBCL/BL) listed in the 2008 WHO classification, are mature B-cell non-Hodgkin lymphomas. They were characterized by a high degree of proliferation with an aggressive clinical course. With the introduction of dose intense, rapid-cycling chemotherapy (Magrath 1996), mainly when supplemented with Rituximab, the prognosis of BL was improved. Conversely, the issue of intermediate DLBCL/BL treatment is still a matter of debate. On this basis, we conducted a retrospective analysis to investigate the outcome of adult patients with BL and intermediate DLBCL/BL treated in a single hematological center. Methods. We retrospectively analyzed 23 adult patients divided in two groups according to histological diagnosis treated with Rituximab plus dose intense rapid-cycling chemotherapy with intrathecal CNS prophylaxis. Group 1: 18 adult BL patients, including three with a diagnosis of L3 acute lymphoblastic leukemia, treated according to CODOX-M/IVAC regimen including Cyclophosphamide, Doxorubicin, Vincristine, Methotrexate, Ifosfamide, Etoposide and high dose Cytarabine in association with Rituximab and intrathecal liposomal Cytarabine (R-CODOX-M/IVAC). Group 2: five intermediate DLBCL/BL, treated with Rituximab intensified CHOP with intrathecal Methotrexate followed by high dose Cytarabine and Mitoxantrone and high dose chemotherapy with autologous stem cell transplantation (R-HDC plus ASCT) or with R-CODOX-M/IVAC. Results. Group 1 included 18 patients with a median age of 45 years (range 29–74), stage IV in 14 cases (78%), performance status (PS) 2 in 14 (78%), LDH upper normal value in 13 (72%), bone marrow involvement in eight (44%), B symptoms in eight (44%) and liquor positivity at citoflussimetry in one (5%). Between 2006 and 2011 all 18 patients were treated according to R-CODOX-M/IVAC. Group 2 included five patients with median age of 47 years (range 32–58), stage IV in four patients (80%), PS 2 in all patients, LDH upper normal value in four (80%) bone marrow involvement in three (60%), B symptoms in three (60%) and liquor positivity at citoflussimetry in two (50%). Between 2008 and 2011 two patients were treated with R-HDC plus ASCT while the other three patients were treated with R-CODOX-M/IVAC regimen. All 18 BL patients of group 1 were evaluable for response: 15 patients were in persistent complete remission (CR) and three died of progressive disease. With a median follow-up of 70.3 months, progression free survival and overall survival were 76.5% and 80.3%, respectively. Therapy was well tolerated, with no significant acute and late treatment related toxicities and no toxic deaths. In group 2 the two patients treated with R-HDC plus ASCT died of progressive disease; of the three patients treated with R-CODOX-M/IVAC regimen, one died of early relapse disease occurred three months after achieving CR and two are still on therapy. Conclusions. Our data suggest that in BL R-CODOX-M/IVAC is a safe and highly effective therapeutic regimen providing a high rate of persistent CR. Within the limits of a small sample size, in our experience, patients with intermediate DLBCL/BL have a clinical aggressive disease with a poor prognosis regardless of the type of treatment. Additional and larger studies are warranted to clarify the behavior of this new histological entity and develop novel and efficacy therapeutic approaches. Disclosures: Vitolo: Roche Italy: Speakers Bureau; Celgene: Speakers Bureau; Jannsen-Cilag: Speakers Bureau.

Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

Addition of R-HMA to R-DA-EPOCH Favourably Changes the Outcome in Patients with Untreated High-Grade Diffuse Large B-Cell Lymphoma: The First Results of Russian Prospective Multicenter Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2708-2708
Author(s):  
Olga A. Gavrilina ◽  
Eugene E. Zvonkov ◽  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Nelly G. Gabeeva ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Grade ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Approximately 50% of diffuse large B-cell lymphomas (DLBCL) are defined as high-grade by IPI. They are characterized by aggressive course and poor response to standard chemotherapy (CT): 5-years overall survival (OS) rate of less than 30%. R-DA-EPOCH has demonstrated very optimistic results (overall and progression-free survival (PFS) were 90%), but high-risk patients (IPI 3-4) showed only 43% of OS and PFS [1]. The addition of high-dose AraC (12 g/m2) to the upfront therapy of high-risk DLBCL has significantly improved the outcome on Hyper-CVAD/HMA and mNHL-BFM-90 protocols [2, 3]. But high toxicity of these protocols restricts their application. We suggested that addition of courses R-HMA in rotation with R-DA-EPOCH could improve the treatment outcome and decrease toxicity. Aim: To evaluate the efficacy and toxicity of R-DA-EPOCH/R-HMA protocol in patients with untreated high-grade diffuse large B-cell lymphoma. Patients and Methods: 33 untreated DLBCL patients from 4 centers were enrolled in a prospective study between August 2013 - July 2015; stage II-IV; ECOG 0-3; median age 55 years (27-76); age ≥60y/<60y 50%/50%; M/F 60%/40%; IPI: 48% high-intermediate and 52% high risk; 15% with bone marrow involvement. All patients underwent 4-8 courses (2-4 cycles) of chemotherapy: R-DA-EPOCH (standard dose and scheme), R-HMA (R 375 mg/m2 d1, MTX 1000 mg/m2 24 hours d 2, AraC 3000 mg/m2 q 12 hrs d 3-4). For patients older than 60 year dose of R-HMA was reduced (R 375 mg/m2 d1, MTX 500 mg/m2 24 hours d 2, AraC 1000 mg/m2 q 12 hrs d 3-4). In 4 cases of DLBCL with bone marrow involvement BEAM conditioning and autologous stem cell transplantation were applied. Results: The median follow-up is 12 months (4-24). There was no mortality associated with toxicity. The main non-hematological toxicities of R-HMA were infections (mucositis, pneumonia, sepsis, enteropathy) grades 1-2 and 3-4 in 90% and 10%, respectively. Hematological toxicity grade 4 for less than 4 days we observed only after courses R-HMA. Complete remission (CR) was achieved in 29 (88%) patients. In 2 patients we observed progression of the disease after first cycle of chemotherapy, in another 2 cases - partial remission after 2-3 cycles and following progression of disease. In patients older than 60 years with doses reduction in R-HMA failures were absent, except one later relapse after 13 month CR. With a median follow 12 months overall and disease-free survival of 33 patients constituted 90,5% and 74% , respectively. In a group of patients older than 60 years results of therapy seemed to be better than in young patients: OS were 100% vs 85,6% (p=0,1), DFS were 80% vs 74,9% (p=0,2), respectively. So the combination of R-DA-EPOCH/R-HMA may be considered as optimal intensive approach in the older patients. Conclusions: TheR-DA-EPOCH/R-HMA protocol demonstrated acceptable toxicity and high efficacy in patients with high-grade DLBCL. This protocol has shown optimistic results in the elderly patients and it could be recommended for further investigation in that group. Ññûëêè: 1. Salit RB, Fowler DH, Wilson WH, et al. Dose-adjusted EPOCH-rituximab combined with fludarabine provides an effective bridge to reduced-intensity allogeneic hematopoietic stem-cell transplantation in patients with lymphoid malignancies.J Clin Oncol. 2012. 10;30(8):830-6. 2. Oki Y, Westin JR, Vega F, et al. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol 2013; 163(5):611-20. 3. Magomedova AU, Kravchenko SK, Kremenetskaia AM, et al. Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma. Ter Arkh. 2011;83(7):5-10. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Comparison of salvage therapies for relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19037-e19037 ◽  
Author(s):  
Venkata Vosuri ◽  
Ravi Kaisreddy ◽  
Somasekhar Bandi
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
High Dose Cytarabine ◽  
Large B Cell

e19037 Background: Salvage chemotherapy followed by autologous stem cell transplantation(ASCT) is the standard second-line treatment for relapsed or refractory diffuse large b-cell lymphoma(DLBCL). Rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE) and rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP) are the two widely used regimens worldwide but quest for optimal regimen continues. Our objective is to compare currently available salvage therapies based on complete response and adverse events. Methods: Pubmed, EMBASE and Clinicaltrials.gov were queried for salvage therapies in relapsed or refractory DLBCL. Only randomized clinical trials including phase 2 and 3 trials involving salvage therapies for relapsed or refractory DLBCL were selected. Data was extracted based on meta-analysis guidelines by two independent reviewers. Network meta-analyses of treatment effects and adverse outcomes were calculated with a frequentist approach. Results: Overall, 5 studies(1480 patients) were included. The salvage therapies investigated were rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE), rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP), rituximab plus gemcitabine, dexamethasone, cisplatin(R-GDP), ofatumumab plus dexamethasone, cytarabine, and cisplatin(O-DHAP), ifosfamide plus ofatumunab, carboplatin, and etoposide(O-ICE), dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide(DR-ICE). Of the 6 regimens in the network, treatment with R-DHAP (OR:0.36,95%CI:0.24-0.54), R-GDP(OR:0.37,95%CI: 0.21-0.65), O-ICE(OR:0.16,95%CI: 0.05-0.53), O-DHAP(OR:0.30,95%CI:0.17-0.52), DR-ICE(OR:0.77,95%CI:0.40-1.49) were not superior against network placebo(R-ICE) in achieving complete response. Higher odds of occurring severe adverse events was observed in R-DHAP(OR:2.02,95%CI: 1.35-3.01) and O-DHAP(OR:2.15,95%CI: 1.24-3.72) salvage regimens when compared to R-ICE. Conclusions: R-DHAP, R-GDP, O-ICE and O-DHAP were found to have no difference in treatment effect in achieving complete response in comparison to R-ICE. R-DHAP and O-DHAP are associated with higher number of severe adverse events in comparison with R-ICE. Outcomes mentioned above should be interpreted in the context of drugs and other factors involved in the disease.

scholarly journals EZH2 Upregulation Is Associated with Unfavorable Prognosis in Diffuse Large B-Cell Lymphoma through Potential RUNX3 Downregulation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5301-5301
Author(s):  
Denise Peker ◽  
Samara Roman-Holba ◽  
Yuri Kwon ◽  
Jennifer Gordetsky ◽  
Amitkumar Mehta ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rna Expression ◽  
Large B Cell Lymphoma ◽  
Group 3 ◽  
Group 2 ◽  
Large B Cell ◽  
Group 1

Abstract Introduction: The runt-related transcription factor 3 (RUNX3) is a downstream effector of the transforming growth factor-β (TGF-β) signaling pathway, and has critical roles in apoptosis, angiogenesis, cell migration and invasion. Putative tumor suppressor activity of RUNX3 has been presented extensively in the literature, particularly in solid epithelial tumors and recently in lymphoma with loss of expression favoring tumorigenesis and/or prognosis, but its role in diffuse large B-cell lymphoma (DLBCL) has not been studied. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. RUNX3 downregulation due to EZH2 upregulation has been shown in various solid tumors. In the present study, we investigated the EZH2 and RUNX3 RNA expression status in DLBCL and its impact on clinical outcome. Methods: A retrospective chart review was performed and 169 cases of DLBCL treated with chemoimmunotherapy between 2003 and 2013 were included. Immunodeficiency- or EBV-associated and MYC+ LBCL were excluded. Archived formalin-fixed-paraffin-embedded tissue samples were retrieved and RNA was extracted using commercially available kits. We correlated the RNA expression levels for EZH2 and RUNX3 in various sites using quantitative real-time PCR (Taqman assay) and custom designed primers for each gene. Control samples included three benign lymph nodes free of a neoplastic process. Results: We identified 66 cases of DLBCL, including25 nodal DLBCL and 41 extranodal DLBCL, with sufficient RNA extracted. Extranodal locations included testis (n=12), orbit (n=6), primary central nervous system (n=5), bone (n=3), breast (n=2) and viscera (n=13). The median age was 64 years (range 29- 81 years) with a female to male ratio of 0.4 (F=20 and M=46). Median overall survival (OS) was 28 months (1-156 months). Immunophenotypic subtype based on cell-of-origin using Hans algorithm was available in 63 cases; 34 cases were germinal center B-cell (GCB) type while 29 were non-GCB type. Treatment data was available in 63 cases and all patients received R-CHOP as initial therapy except three patients who died shortly after diagnosis. Forty-four cases showed higher expression of EZH2 and RUNX3 when compared to normal lymph nodes (p < 0.05). Nineteen out of 44 cases showed increased EZH2 and decreased RUNX3 expression (Group 1) while EZH2 expression was lower than RUNX3 in the remaining cases (Group 2). The remaining 22 DLBCL cases did not show significant correlation for expression (Group 3). Overall survival was significantly low in Group 1 compared to Group 2 and Group 3 (p =0.030 and p=0.026, respectively). There was no difference for OS between Groups 2 and 3 (p>0.05) (Figure 1). Conclusions: Our results showed that decreased RUNX3 RNA expression is associated with EZH2 overexpression and poses an adverse prognostic factor in DLBCL. Larger studies are needed to establish the prognostic and therapeutic utility of EZH2 and/or RUNX3. Disclosures Mehta: Pharmacyclics: Research Funding; Merck: Research Funding; Incyte: Research Funding; Medimmune: Research Funding; Roche Genentech: Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Forero:University of Alabama at Birmingham: Research Funding. Costa:Sanofi: Honoraria, Research Funding.

Reduced Specificity and Positive Predictive Value of Surveillance FDG-PET/CT for Diffuse Large Cell B Cell Lymphoma in the Rituximab Era

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1576-1576
Author(s):  
Irit Avivi ◽  
Ariel Zilberlicht ◽  
Eldad J Dann ◽  
Jacob M. Rowe ◽  
Ronit Leiba ◽  
...  
Keyword(s):  
B Cell ◽  
Predictive Value ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Pet Ct ◽  
Group 2 ◽  
Fdg Pet Ct ◽  
Group 1

Abstract Abstract 1576 Background: Surveillance PET is reported to allow the detection of asymptomatic relapses in a substantial number of patients with diffuse large cell B cell lymphoma (DLBCL). Recent data suggest that rituximab (R) administration results in a higher incidence of false positive (FP)“end-therapy” scans. However, the predictive value (PV) of surveillance PET in patients receiving R versus chemotherapy has not been fully explored. Objectives: The current study compared the PV of surveillance PET in patients with DLBCL receiving CHOP-R therapy versus CHOP alone. Patients and Methods: This retrospective study was approved by the IRB of the Rambam Health Care Campus (Haifa, Israel). The institutional database was searched for all newly diagnosed adult patients with DLBCL, treated with the CHOP or CHOP-R between January 1995–2008, who achieved complete remission (CR), had at least one follow-up (FU) FDG PET/CT during remission and were followed until relapse/death, or for at least 12 months after the last FU scan. The routine FU protocol included PET scans, performed at 3, 6, 12, 18, 24, 36, 48 and 60 months after CR. Demographic, clinical and imaging data at disease staging, during FU and at recurrence were collected and analyzed separately for patients treated with CHOP alone (group 1) and for those receiving CHOP-R (group 2). The ability of PET-FU to detect recurrence was assessed for the whole cohort, depending on rituximab administration, duration of CR, and location of suspicious findings. All scans were originally reviewed by 2 PET specialists, and positive scans were re-evaluated using the same criteria as those employed to report initial findings. PET-FU was considered positive in the presence of an uptake unrelated to physiological bio-distribution or a known benign process. PET-FU results were confirmed by biopsy or further imaging and clinical FU. Results: 119 patients, 35 treated with CHOP and 84 with CHOP-R, were analyzed. Median age was 59 years (24–88); 59% presented with an advanced stage (III-IV) and 45% had an IPI score ≥2. There were no statistically significant differences in patient characteristics in the 2 groups, except for a shorter median FU period for patients receiving R (2.9 vs 6.4 years, p<0.0001). Within a median FU of 3.4 years (0.6–8.6), 31 patients relapsed (17 confirmed histologically), 14 in the CHOP-R group (15%) vs 17 in the CHOP cohort (47%), (p=0.02). Nine (29%) relapses were initially detected by PET-FU in asymptomatic patients, with no difference in the incidence of these relapses between the 2 groups. Relapse involved the original sites in 85% of cases, with no differences between the groups. A total of 422 PET studies were performed; 113 in group 1 and 309 in group 2. Eighty three studies were judged to be positive, 23 in group 1 and 60 in group 2. However, in the CHOP-R group, only 23% (14/60) were truly positive compared to 74% (17/23) in the CHOP group (p=0.001).The median time to FP PET was significantly longer for patients receiving CHOP-R (1.3 vs 0.6 years, p=0.03). Specificity and positive PV (PPV) were significantly lower for patients receiving CHOP-R compared to those treated with CHOP only (Table 1). An FDG uptake involving head and neck lymph nodes was more likely to be FP, especially in group 2 (88% vs 4%, p=0.0004). Furthermore, age younger than 60 years and earlier disease stage were also found to be significantly associated with an increased incidence of FP results, particularly in patients receiving R. Conclusions: Surveillance PET in patients with DLBCL is highly sensitive for the detection of recurrence, providing the first indication of relapse in 29% of patients. However, comparative analysis shows that specificity of PET-FU is significantly lower in the R era, yielding a PPV of only 23%. Interestingly, late FP PET, involving nodal sites, uniquely observed in patients receiving R, is assumed to reflect lymph node “recovery” following the R-induced B cell depletion. The emerging data emphasize the limitations of surveillance PET in the R era and the need for an efficient algorithm for its use in this setting. Disclosures: No relevant conflicts of interest to declare.

Retrospective analysis of CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) treated with chemotherapy with or without rituximab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8551-8551
Author(s):  
K. Miyazaki ◽  
M. Yamaguchi ◽  
R. Suzuki ◽  
N. Niitsu ◽  
D. Ennishi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Elevated Serum ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Significant Difference ◽  
Large B Cell

8551 Background: CD5+ DLBCL comprises 5–10% of DLBCL, and shows a high incidence of central nervous system (CNS) relapse. It has been included in the 4th WHO classification as an immunohistochemical subgroup. To clarify the prognosis and incidence of CNS relapse of CD5+ DLBCL in the rituximab-era, we conducted a multicenter retrospective study. Methods: We analyzed 313 patients (pts) with CD5+ DLBCL who received chemotherapy with (n=164) or without rituximab (n=149). The current series includes 107 out of 120 pts described in our previous study (Haematologica, 2008). Intravascular large B-cell lymphoma, primary CNS DLBCL, and secondary CD5+ DLBCL were excluded from the study population. Results: 313 pts showed the following clinical features: median age, 67 (range: 15–93); M:F=163:150; elevated serum LDH level, 71%; stage III/IV, 64%; IPI HI/H, 53%. No significant difference in clinical background such as the IPI and its five components, B symptom, male sex, and bone marrow involvement was found between pts who were treated with and without rituximab. Pts treated without rituximab received more dose-intensive chemotherapies (CHOP14, third-generation regimen, and high dose cytarabine-based regimen) than those treated with rituximab (24% vs. 7%, P<0.0001). The CR rate was higher in pts received rituximab than those without (81% vs. 65%; P=0.0014). The median follow-up was 28 months in pts who received rituximab (range: 7–77) and 68 months in those who did not (range: 6–187). Overall survival (OS) was significantly superior for pts with rituximab than for those without (2-yr OS: 68% vs. 54%, P=0.003). Multivariate analysis revealed that the use of rituximab was favorably associated with OS (HR=1.81, 95% CI: 1.26–2.58, P=0.001), but dose-intensive chemotherapies did not affect OS. However, the incidence of CNS relapse was not different between the two groups (2-yr CNS relapse rate: 11.9% vs. 11.4%, P=0.91). 16 of the 20 pts (80%) with CNS relapse in the rituximab group had brain parenchymal disease. Conclusions: Our data show that rituximab improves OS of pts with CD5+ DLBCL, but does not prevent CNS relapse. Future prospective studies to decrease CNS disease for CD5+ DLBCL are warranted. No significant financial relationships to disclose.

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

scholarly journals Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Wilfred Delacruz ◽  
Robert Setlik ◽  
Arash Hassantoufighi ◽  
Shyam Daya ◽  
Susannah Cooper ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Unmet Need ◽  
Case Series ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Hematologic Malignancies ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
First Line

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted.

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