Specific Chemotherapy and Rituximab In HIV-Infected Patients with Burkitt's Leukemia or Lymphoma. Results of a German-Spanish Study and Analysis of Prognostic Factors
Authors: Ribera Josep-Maria , Wyen Christoph , Morgades Mireia , Hoffmann Christian , Oriol Albert , Fätkenheuer Gerd , Grande Carlos , Mueller Markus , Esteve Jordi , Wasmuth Jan-Christian , Del Potro Eloy , van Lunzen Jan , Brunet Salut , Knechten Heribert , Escoda Lourdes , Hammond Angela , Alonso Nuria , Hentrich Marcus , Vall-llovera Ferran , Mayr Christoph , Perez Montserrat , Thoden Jan , Garcia Olga , Sternfeld Thomas , Wolf Timo , Sanz Miguel-Angel , Hoelzer Dieter 
Published: October 2019

Abstract
Abstract 3944
Background and objective. Specific immunochemotherapy has provided promising results in HIV-infected patients with Burkitt's leukemia or lymphoma (BLL), not significantly different from those observed in non-immunosuppressed patients. The results and prognostic factors in 72 HIV-positive patients with BLL treated with the same protocol in Germany and Spain are presented. Patients and method. Treatment consisted of a prephase with cyclophosphamide and prednisone, followed by cycles (A, B, C) including rituximab, iphosphamide, and high-dose methotrexate and cytarabine, among other drugs. CNS prophylaxis consisted of triple intrathecal therapy (MTX, cytarabine and dexamethasone). Reduction in the doses of MTX and ARAC was scheduled for pts. older than 55 yr. Patients in localized stages (I, II) received 4 cycles (A1,B1,C1 and A2) and those in advances stages (III, IV) or Burkitt's leukemia received 6 cycles (A1, B1, C1, A2, B2, C2) followed by 2 additional doses of rituximab at the end of chemotherapy. Response was evaluated after two cycles of chemotherapy (A1, B1).Results. 34 pts from Spain and 38 from Germany were included. No differences in the clinicobiologic characteristics or in the HIV-infection parameters were observed between the two cohorts, except for the increased use of highly active antiretroviral therapy (HAART) in the Spanish cohort before BLL diagnosis (73% vs. 6%). Overall, median age was 43 yr (range 20–69) and 66/72 (92%) pts were male, 53 pts (75%) were in advanced stages (III-IV), with extranodal involvement in 57/71 (80%) (bone marrow in 24 cases).LDH was elevated in 48 (68%) pts. ECOG score was >2 in 33 (46%) pts. Median time between HIV and BLL diagnoses was 3 (0-22) yr, mean CD4 lymphocyte count/mL 294 (SD 232), CD4 <200/mL 27/70 (39%), HIV viral load <50 copies/mL 19/68 (28%), and 26/69 (38%) received HAART before BLL diagnosis. Complete response (CR) was attained in 49 pts (81%), 7 (12%) died in induction and 4 (7%) were resistant, without differences between the two cohorts. No relapses have been observed after a median follow-up of 2.6 (0-5) yr. The overall survival (OS) probability was 74±10%, without significant differences between the two cohorts. By multivariate analysis CD4 count <200/mL (OR 7.2 [95%CI: 1.3–38.6]) and involvement of 3 2 extranodal areas (OR 7 [95%CI: 1.2–40.6]) had a negative influence on CR, whereas the unfavourable prognostic factors for OS were: CD4 count <200/mL (OR 4.4 [95%CI: 1.2–15.8]) and ECOG>2 (OR 4.4 [95%IC 1.1–17.8]). Grade 3–4 hematological toxicity was observed in 96% of the cycles, whereas grade 3–4 mucositis was registered in 30% of cycles and infections in 35%.Conclusions. In HIV-infected pts with BLL specific chemotherapy and rituximab was highly effective, although the toxicity was relevant. Performance and immunologic status and the degree of extranodal involvement were the most important prognostic factors in this series. Supported in part by grants RD06/0020/1056 from RTICC and DJCL SH 06/03.

Disclosures:
No relevant conflicts of interest to declare.