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

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.