Rituximab Based Regimen May Decrease the Incidence of CNS Relapse in Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4770-4770
Author(s):  
Mervat Mahrous Mohamed ◽  
Rena Buckstein ◽  
Eugenia Piliotis ◽  
Matthew C Cheung ◽  
Neil Berinstein
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Cns Involvement ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 4770 BACKGROUND Relapse in the central nervous system (CNS) following initial treatment of diffuse large B-cell lymphoma (DLBCL) is an uncommon but fatal complication. However, the addition of rituximab improves the clinical outcome dramatically in DLBCL patients; its influence on CNS relapse is unproven. Aim This single centre retrospective study was conducted to investigate the incidence of CNS relapse, and to evaluate the impact of adding rituximab to standard CHOP (RCHOP) regimen without CNS prophylaxis in patients at risk of CNS relapse. PATIENTS AND METHODS All patients with DLBCL diagnosed from April 2002 to December 2007 at sunnybrook cancer center were retrospectively identified in the Cancer Database. Patients were included if they were >16 years old, had advanced stage (stage III /IV, or stage I /II with B symptoms, elevated LDH or bulky disease, were treated with RCHOP regimen with curative intent and were free of CNS involvement at diagnosis. CNS relapse was diagnosed by CSF cytology, radiology or clinically. Results A total of 155 patients were newly diagnosed with DLBCL and treated with RCHOP only. 22 pts were excluded, 20 had CNS prophylaxis and 2 pts had CNS involvement. 133 pts were eligible (69 male and 64 female) Median age was 64 (Age'60 was 59.4%). Stage III/IV was 69.9%. LDH was elevated in 59.4%. Bone marrow (BM) involvement and Extra nodal “>2 were 18.05% and 25.6% respectively. EN sites were: (liver 4.5%, Bone 6.8%, Pulmonary 4.5%, kidney 3.01%, cardiac 1.5%, intestine 2.3%, testicular 1.5%). The International Prognostic Index was high-intermediate/high in 55.6%. Pathologically transformed was 12.03% and were transformed from indolent histologies. BCL2 was positive in 65.4%, BCL6 was 48.9%, CD10 was positive in 49.6%, Ki-67 was >80% in 25%. All patients received RCHOP (Median 6 cycles, (range 2-8). Overall response (ORR) was 88.6%, CR/CRU 72.7% with a median follow up 24.6 months (range 2.6-75.5). 28 patients (21.05%) relapsed systemically. Two patients (1.5%) had a CNS relapse 1 brain parenchyma and 1 leptomeningeal one month after systemic relapse. The median time to CNS relapse was 10.4 mos (6.24-14.5 mos). In univariate risk factor analysis (LDH (p=0.8), IPI>3 (p=0.9), No of EN (p=0.9). Actuarial 5 y Overall Survival (OS) was 67.3% (95% CI (57-77%) and progression free Survival (PFS) was 65.7% (95% CI (52.3-78.6%). Conclusion Our data suggest that the addition of rituximab may reduce the risk of CNS relapse for poor risk patients likely through systemic control. Future prospective studies of rituximab-containing chemotherapies with CNS prophylaxis are warranted Disclosures: No relevant conflicts of interest to declare.

scholarly journals Intrathecal (IT) Chemotherapy for Central Nervous System (CNS) Prophylaxis in Diffuse Large B-Cell Lymphoma (DLBCL): A Single Centre Retrospective Observational Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Luke Attwell ◽  
Benjamin Gray ◽  
Rachel Hall ◽  
Sally Killick ◽  
Helen McCarthy ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Educational Meetings ◽  
Large B Cell

Introduction: CNS relapse of DLBCL is associated with poor prognosis. Estimated incidence varies between 1.9 and 8.4%1. The CNS-International prognostic index (IPI)2 help risk stratify and estimate the 2-year risk of CNS relapse in DLBCL patients treated with R-CHOP chemotherapy. CNS prophylaxis is indicated in patients with a high risk of CNS relapse (a score of ≥4 equated to a 10.2% risk). High-risk DLBCL patients outside the CNS-IPI system include double/triple-hit (MYC/BCL-2/BCL-6 translocations) lymphoma, HIV lymphoma, testicular lymphoma, primary cutaneous lymphoma-leg type, stage IE breast lymphoma3. IT methotrexate or cytarabine administered during the course of systemic chemotherapy has been the most widely employed method of CNS prophylaxis but there is paucity of data validating its efficacy. Aim: The primary aim of the study was to evaluate the CNS relapse rates in DLBCL patients who received CNS prophylaxis. Patients and Methods: This was a single-centre retrospective observational study conducted in a district general hospital. Data was extracted from the regional (Dorset Cancer Network) DLBCL database and laboratory reports for CSF analysis at the time of the first intrathecal chemotherapy. Medical records of patients with DLBCL who received CNS prophylaxis were evaluated for the following patient-related and disease-related demographics: age at diagnosis, gender, stage, systemic treatment, CNS prophylaxis, treatment response, remission duration, systemic relapse rates, CNS relapse rates and survival. CNS-IPI scores were retrospectively calculated and additional indications evaluated for patients who received CNS prophylaxis. Results: Between 2013 and 2018, 178 patients were diagnosed with DLBCL. All patients were treated with RCHOP chemo-immunotherapy. CNS prophylaxis was administered in 47 (26%) patients. Median age was 69 years (range 20-86 years) and 62% were males. All 47 patients (100%) received IT methotrexate as CNS prophylaxis, with 43 (91%) receiving all of the planned 4 doses of IT methotrexate 12.5 mg each. A CNS-IPI score of ³4 was present in 31 (66%) patients, and a score of 2-3 in 9 (19%) patients. Additional risk factors identified included testicular lymphoma in 3 patients, breast lymphoma in 2 patients and oropharyngeal lymphoma in 2 patients. Ten (21%) patients received their treatment at the outset with courses 1-4 of R-CHOP. Of the 47 patients who received CNS prophylaxis, 5 (10%) relapsed; all had isolated CNS lymphoma at relapse. Median time to CNS relapse was 25 months (range 12-36 months) from initial diagnosis of DLBCL. Median survival after CNS relapse was 5 months (range 2-9 months). Of the remaining 141 patients, 2 patients relapsed with isolated CNS lymphoma. Conclusion: Although the overall incidence was low (4%), CNS relapse was observed in 10% of high-risk patients all of whom received CNS prophylaxis with IT methotrexate. The efficacy of CNS prophylaxis with IT chemotherapy remains unproven. There is no randomised study to show that IT prophylaxis alone is effective. Current British guidelines recommend high-dose intravenous methotrexate over IT methotrexate if patient's physiological fitness and renal function are acceptable4. The median age in our cohort was 69 years which makes it challenging to deliver dose-intensive systemic therapy concurrently with intravenous high-dose methotrexate. The role of CNS prophylaxis in high-risk patients including its efficacy and safety in older patients need further evaluation in prospective randomised studies. References Eyre T et al.Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review. Hematologica. 2019;105(7):1914-1924.Norbert Schmitz et al.CNS International prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOPJ Clin Oncol 2016; 34:3150-3156.Andrew D Zelenetz et al.National Comprehensive Cancer Network (NCCN) Guidelines: B-Cell Lymphomas.Version 2.2020.Pamela McKay et al.The prevention of central nervous system relapse in diffuse large B-cell lymphoma: a British Society for Haematology good practice paper. Onlinelibrary.wiley.com. 2020. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16866 Disclosures Hall: Janssen:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Karyopharm:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Takeda:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings.Killick:Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Jazz Pharmaceuticals:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Gilead:Honoraria, Other: Support for attending education meetings.McCarthy:Janssen:Honoraria;Abbvie:Membership on an entity's Board of Directors or advisory committees.Walewska:AbbVie:Other: sponsored for educational meetings, Speakers Bureau;Janssen:Other: sponsored for educational meetings, Speakers Bureau;Gilead:Speakers Bureau;Astra Zeneca:Membership on an entity's Board of Directors or advisory committees.Chacko:Astellas:Honoraria;Daiichi-Sankyo:Honoraria;Novartis:Honoraria, Other: Travel Grants;Gilead:Other: Travel grants;Jazz Pharmaceuticals:Other: Travel grants;Celgene:Other: Travel grants.

Central Nervous System Relapse in Patients with Diffuse Large B-Cell Lymphoma: Analysis of Incidence and Prognostic Factors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1666-1666
Author(s):  
Masahiro Uni ◽  
Yuki Kagoya ◽  
Yasuhito Nannya ◽  
Fumihiko Nakamura ◽  
Mineo Kurokawa
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Initial Diagnosis ◽  
High Dose ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

Abstract The addition of rituximab to CHOP (R-CHOP; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisolone) has significantly improved the outcome of diffuse large B-cell lymphoma (DLBCL). However, its secondary involvement in the central nervous system (CNS) is still a fatal event, and optimal therapeutic strategies have remained to be established. Combined immunochemotherapy with rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy and high-dose cytarabine is currently in use for patients with CNS relapse, though treatment outcome has not been evaluated enough. In the present study, we aimed to analyze the incidence and prognosis of CNS relapse of aggressive B-cell lymphoma in comparison with those of systemic relapse in the era of rituximab-containing regimens. We also estimated the risk factors and prognostic factors for CNS relapse. We retrospectively analyzed 278 consecutive adult patients (≥16 years old) who were diagnosed as DLBCL or primary mediastinal large B-cell lymphoma (PMLBL) at The University of Tokyo Hospital, Tokyo, Japan, from August 2003 through August 2013. We excluded patients who had CNS or intraocular involvement at diagnosis since those patients had received high-dose methotrexate-based therapy instead of R-CHOP. Four to six courses of intrathecal administration of methotrexate were performed in patients with adrenal gland, testis or breast involvement as prophylaxis for CNS relapse. The median follow-up period was 42 months, and the median age was 66 years (range, 23-91). Overall, 67 patients (24.1%) had relapse at any site, of which 24 patients (35.8%) had CNS involvement. The median interval between initial diagnosis and the occurrence of secondary CNS involvement was 212 days, and 15 of the 24 patients (62.5%) had CNS relapse within 1 year from the initial diagnosis. Multivariate analysis revealed that multiple or diffuse extranodal involvement at initial diagnosis (hazard ratio [HR] 3.74, 95% confidence interval [CI] 1.28-10.91; P<0.01) was associated with the development of CNS relapse against non-CNS relapse. Chromosomal abnormality was investigated in 112 patients, of which 38 had abnormal karyotypes as identified by G-banding analysis for lymph nodes. Patients with CNS relapse more frequently harbored chromosomal abnormalities compared with those without relapse in univariate analysis (P=0.01). We also analyzed the survival of patients with primary CNS lymphoma (PCNSL) as a control. Only two (7%) of 27 patients with PCNSL died during the follow-up period. Five-year OS from initial diagnosis was 92.3% (95% CI: 82.5-100.0%), and was significantly better than that for patients with CNS relapse (33.9%, 95% CI: 17.3-66.3%, P<0.01). Among 24 patients with CNS relapse, eight (33%) had systemic lesions other than CNS when diagnosed as CNS relapse, and four (17%) patients newly developed systemic lesions while treated for CNS relapse. Patients without concurrent systemic lesions attained a rather good prognosis by chemo-radiotherapy, while those harboring concurrent systemic lesions had dismal outcome (one-year OS after the diagnosis of relapse: 74.0% versus 12.4%, P<0.01, Figure 1, systemic relapse was treated as a time-dependent covariate). These results indicate that controlling systemic lesions as well as CNS ones is essential for treating patients with secondary CNS involvement of DLBCL. CNS lesions would be well controlled with R-MPV implementation as salvage therapy, nevertheless we should be careful for concurrent systemic lesions which might require different therapeutic strategies. Disclosures Nannya: Chugai Pharmaceutical　CO., LTD: Speakers Bureau; Pfizer: Research Funding. Kurokawa:Chugai Pharmaceutical　CO., LTD: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding.

scholarly journals Favorable Outcomes with Thiotepa/Busulfan-Based Conditioning and Autotransplant for Patients with Aggressive B-Cell Lymphoma and Secondary CNS Involvement

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2912-2912
Author(s):  
Robert Puckrin ◽  
Neil Chua ◽  
Mona Shafey ◽  
Douglas A. Stewart
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell ◽  
Aggressive B Cell Lymphoma

Abstract Introduction : Central nervous system (CNS) relapse is a devastating complication affecting ~5% of patients with diffuse large B-cell lymphoma (DLBCL). The optimal management is unknown and survival rates are ~20% in contemporary series. Thiotepa/busulfan-based high-dose chemotherapy (HDT) and autotransplant (ASCT) has demonstrated efficacy in primary CNS lymphoma, but there have been fewer studies of this conditioning regimen in secondary CNS lymphoma (SCNSL). Methods : This multicenter retrospective study included all consecutive patients ≥18 years old with aggressive B-cell lymphoma and secondary CNS involvement treated with thiotepa/busulfan-based HDT/ASCT at the University of Calgary and University of Alberta since 2005. Kaplan-Meier curves were used to estimate progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) from the time of ASCT. Data collection is underway for all consecutively diagnosed SCNSL patients at our institutions to evaluate frequency and predictors of HDT/ASCT use. Results : This study included 57 patients with DLBCL (n=45), double-hit lymphoma (n=6), high-grade B-cell lymphoma NOS (n=2), intravascular large B-cell lymphoma (n=2), or T-cell/histiocyte-rich large B-cell lymphoma (n=2). Two (4%) had previously treated indolent B-cell lymphoma and 1 (2%) had multiply relapsed DLBCL. Median International Prognostic Index was 4 (range 0-5) at DLBCL diagnosis and median time to CNS relapse was 4 months (range 0-139). Median age was 58 years (range 20-73) and median ECOG was 3 (range 0-4) at diagnosis of SCNSL. CNS involvement was present at initial diagnosis in 20 (35%) patients or developed during frontline treatment in 10 (18%) or after completion of treatment in 27 (47%). For those without SCNSL at diagnosis, isolated CNS relapse occurred in 31 (84%) patients while 6 (16%) had concurrent CNS and systemic relapse. Most patients (n=54, 94%) received high-dose methotrexate (HD-MTX)-based multiagent induction chemotherapy (median HD-MTX doses 4, range 1-5) followed by peripheral blood stem cell mobilization with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in 41 (72%). HDT conditioning regimens were thiotepa, busulfan, melphalan, rituximab (TBMR, n=52, 91%) or thiotepa, busulfan, cyclophosphamide (TBC, n=5, 9%). Median time from SCNSL diagnosis to ASCT was 116 days (range 7-201). Median time to neutrophil engraftment was 10 days (range 7-15) and to platelet engraftment 16 days (range 9-93). Overall response rates (ORR) for systemic/CNS disease were 93%/89% pre-ASCT and 95%/100% post-ASCT. Combined ORR pre-ASCT was 88%, with complete response in 21% and partial response in 67%. Two (4%) patients who developed CNS relapse immediately prior to ASCT achieved long-term remission after TBMR conditioning without any other systemic chemotherapy. With a median follow-up time of 4.0 years (range 0.1-15.9), PFS was 75% (95% CI 61-85%), OS was 76% (95% CI 62-86%), and DSS was 79% (95% CI 64-88%) at 4 years after ASCT. Lymphoma recurred in 9 (16%) patients at median 88 days (range 54-346) after ASCT with CNS relapse (n=4), systemic relapse (n=3), or both (n=2). There were 2 (4%) deaths due to peri-transplant toxicity and 1 (2%) death at 1.5 years due to therapy-related acute myeloid leukemia; no other unexpected toxicities of HDT/ASCT were observed. Among the 45 (79%) patients achieving long-term disease-specific survival, none were treated with CNS radiation therapy and only 1 (2%) had persistent neurocognitive impairment. There were no significant differences in DSS with respect to timing of CNS relapse, concurrent presence of systemic disease, or TBMR versus TBC conditioning (78% vs 80%, p=0.87). Conclusion : In one of the largest studies of this conditioning regimen in SCNSL to date, we found that high-dose thiotepa/busulfan-based conditioning with ASCT is associated with favorable outcomes for patients with aggressive B-cell lymphoma and secondary CNS involvement, with 4-year OS ~75% in this study. Although SCNSL has been historically associated with a poor prognosis, an increasing proportion of patients may achieve long-term survival after intensive therapy with HD-MTX-based induction and thiotepa/busulfan-based HDT and ASCT. Figure 1 Figure 1. Disclosures Chua: Eisai: Honoraria; Pfizer: Honoraria; Merck: Honoraria; Gilead: Honoraria. Stewart: Novartis: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria; Sandoz: Honoraria; Teva: Honoraria.

CNS Involvement in Childhood and Adolescence Non-Hodgkin Lymphoma: Prevalence and Patient’s Outcome Differ According to the Subtype.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 233-233 ◽  
Author(s):  
Janina Salzburg ◽  
Birgit Burkhardt ◽  
Olga Wachowski ◽  
Martin Zimmermann ◽  
Reza Parwaresch ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Childhood And Adolescence ◽  
Cns Involvement ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract We evaluated the prevalence and clinical significance of CNS involvement in childhood and adolescence Non-Hodgkin Lymphoma (NHL). Between 10/86 and 12/02, 2,086 eligible patients (pts) were registered in the subsequent multicenter trials NHL-BFM86, −90, −95. Median follow up was 6.5 years (0.3–17.7 years). Initial staging included examination of cerebrospinal fluid (CSF) and cranial CT or MRI. CNS involvement was diagnosed in case of CSF blasts, and/or intracerebral mass (ICM), and/or cranial nerve palsy (CNP), not caused by an extradural mass. Epidural NHL without any of the above criteria was not considered as CNS disease. CNS positive (pos) pts with lymphoblastic lymphoma (LBL) received an 8-drug induction, consolidation, re-intensification, and maintenance up to 2 years. CNS therapy included dexamethason, methotrexate (MTX) 5 g/m2 i.v., 13 dosis of intrathecal (i.th.) MTX, and cranial radiotherapy (CRT). CNS pos pts with non-LBL received six 5-day courses based upon vincristine, vindesine, dexamethason, oxazophorins, cytarabine, etoposide, doxorubicin, MTX 5 g/m2 i.v., and intraventricularely or i.th. applied chemotherapy. CRT was omitted since study BFM90, except for pts with anaplastic large cell lymphoma (ALCL). 111 of the 2,086 analyzed NHL pts were initially diagnosed as CNS pos. 1,933 pts were CNS negative (neg) and in 42 pts the CNS status was questionable or not evaluable due to incomplete diagnostics. Prevalence and outcome of CNS pos pts according to NHL subtypes were as follows. In the total group, the probability of event free survival at 5 years (pEFS) was 63 ± 5% for CNS pos pts compared to 81 ± 1% for CNS neg pts with stage III/IV NHL (n=1,323) (p&lt; 0.0001). In LBL pts pEFS was 81 ± 10% for CNS pos pts and 84 ± 2% for CNS neg pts with stage III/IV (n=359) (p=0.54), while in Burkitt/B-ALL pEFS was 60 ± 5 % for CNS pos pts versus 85 ± 1% for CNS neg pts with stage III/IV (n=599) (p&lt;0.0001). For CNS pos Burkitt/B-ALL pts pEFS was 57 ± 7% for 57 pts with and was 67 ± 10% for 24 pts without bone marrow involvement (p=0.31). Total LBL (T-, pB-) Burkitt/B-ALL PMLBL* DLBL° ALCL Others *primary mediastinal large B-cell lymphoma, °diffuse large B-cell lymphoma Number of pts 2086 433 1003 40 222 215 173 CNS pos pts 111 16 81 0 4 5 5 Percentage 5,3% 3,7% 8,1% 0 1,8% 2,3% 2,9% Chracteristics and outcome of CNS pos pts CSF blasts +/ − others 81 13 60 0 1 4 3 ICM (without CSF blasts) 18 2 11 0 2 1 2 CNP 12 1 10 0 1 0 0 Death unrelated to tumor 6 0 6 0 0 0 0 Relapse/Nonresponse 30 2 24 0 0 2 2 CNS involved 18 1 15 0 0 2 0 In summary, CNS-disease was most frequent in pts with Burkitt/B-ALL, while it was rare in DLBL pts. In Burkitt/B-ALL, CNS pos pts had a worse outcome compared to CNS neg pts with advanced stage disease, while in LBL pts outcome was comparable for CNS pos and CNS neg pts.

Central Nervous System Involvement in Patients with Diffuse Large-B Cell Lymphoma: A Retrospective Analysis of a Single Center in Brazil.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5029-5029
Author(s):  
Talita Rocha ◽  
Maeva Pinto ◽  
Sergio Costa Fortier ◽  
Igor Campos ◽  
Roberto Paes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Developed Countries ◽  
Stage Iii ◽  
Cns Involvement ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 5029 Background Relapse in the central nervous system (CNS) after initial treatment of diffuse large-B cell lymphoma (DLBCL) is an uncommon but serious complication. This retrospective study of a single institution in a Latin American country investigated the incidence of CNS involvement in patients with DLBCL and compared it with results in developed countries. Patients and methods A total of 134 patients treated for DLBCL from January 2001 to April 2008 were retrospectively analyzed for incidence of secondary CNS involvement of lymphoma. Results Twenty six (19,4 %) patients of this cohort had used rituximab as first line treatment and nine (6,7%) had done IT chemoprophylaxis. Seventy (52%) were stage III and IV. Forty seven (35%) had high intermediate or high international prognostic index. Nine of 134 (6,7%) developed CNS disease after a median observation of 36 months. The median time for the CNS relapse or progression was 7,7 months after diagnostic and all but one patient died despite the treatment proposed. Among the 9 patients that relapsed, seven (77,7 %) had parenquimal CNS involvement. Seven (77,7%) had stage III or IV disease. One (11,1 %) had bone marrow involvement. Two (22,2%) received IT chemoprophylaxis and 3 (33,3%) had used rituximab. Discussion and Conclusion We describe here our cases and emphasize that as we know, this is the only Brazilian study investigating this kind of involvement. Different than expected, we found a similar CNS infiltration compared to developed countries cohorts. This suggests that CNS disease is probably related to biologic features than circumstantial issues normally present in developing countries such as late diagnoses and treatment. The evaluation of the risk factors for CNS involvement had not been done due to the small cohort. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Diving Bell and the Butterfly Revisited: A Fatal Case of Locked-in Syndrome in a Man With Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

2018 ◽  
Vol 11 ◽  
pp. 1179545X1876279
Author(s):  
Jacqueline N Poston ◽  
Russell Dorer ◽  
David M Aboulafia
Keyword(s):  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Epstein Barr ◽  
Large B Cell

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare variant of DLBCL. The natural history of this subtype is poorly understood. Incomplete literature in the era of rituximab suggests that patients with EBV-positive DLBCL have similar outcomes to patients with EBV-negative DLBCL when treated with rituximab and anthracycline-based chemotherapy regimens; however, there are few prospective studies on this subtype and little is known about the risk of central nervous system (CNS) relapse with EBV-positive DLBCL. Herein, we describe the case of a 64-year-old man who presented with stage IIA EBV-positive DLBCL. His international age-adjusted International Prognostic Index (IPI) was 2. He achieved a complete response to 6 cycles of rituximab combined with chemotherapy consisting of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. After 10 days of completion of chemotherapy, he had a fulminant neurologic decline manifested by diffuse weakness followed by a locked-in syndrome; he could only communicate by moving his eyes. He had been deemed at low risk for CNS relapse based on the application of the recently developed CNS-IPI score of 2 (1 point for age >60 years and 1 point for lactate dehydrogenase higher than normal) and consequently did not receive therapy for CNS prophylaxis. A limited postmortem autopsy revealed extensive lymphoma throughout the brain, particularly in the deep basal nuclei, midbrain, pons, centrum semiovale, and corpus callosum. This presentation of CNS relapse is rare and has not yet been described in EBV-positive DLBCL. We discuss some of the unique aspects of this case including the clinical manifestations of locked-in syndrome and its differential diagnosis and the uncertain benefits of CNS prophylaxis in this clinical context.

scholarly journals Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Sabela Bobillo ◽  
Erel Joffe ◽  
David Sermer ◽  
Patrizia Mondello ◽  
Paola Ghione ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Relapse Risk ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

AbstractAlthough methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.

scholarly journals Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Harrysson ◽  
Sandra Eloranta ◽  
Sara Ekberg ◽  
Gunilla Enblad ◽  
Mats Jerkeman ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Refractory Disease ◽  
Curative Intent ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

AbstractWe performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007–2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7–66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7–24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5–3.6, n = 118) overall, and 8.0% (95% CI: 6.0–10.6, n = 48) among patients with high CNS-IPI (4–6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.

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