Specific Intensive Chemotherapy Plus Rituximab for Advanced Burkitt's Lymphoma or Leukemia in HIV-Positive and Negative Adult Patients.

Abstract

A previous PETHEMA protocol (PETHEMA ALL3/97) proved that HIV-positive patients with Burkitt's lymphoma (BL) and Burkitt-like acute lymphoblastic leukemia (ALL3) had similar outcome than HIV-negative patients (Haematologica 2003; 88:445–53). We aimed to study the impact of the addition of rituximab to our previous protocol in terms of toxicity and efficacy, with special attention to HIV-positive patients. Consecutive patients between 18 and 55 years and diagnosed with advanced stage (stage III-IV or bulky stage II) BL/ALL3 between July 2003 and August 2006 received induction therapy including a pre-phase with cyclophosphamide (CPM) and prednisone (PDN), followed by cycle A (rituximab, iphosphamide, VCR, dexamethasone -DXM-, HD-MTX, ARA-C and VM-26), cycle B (rituximab, VCR, HD-MTX, CPM, DXM and doxorubicin) an cycle C (rituximab, DXM, VDN, HD-MTX, HD-ARAC and VP-16) up to six cycles (A1,B1,C1,A2,B2,C2) followed by two additional rituximab doses. CNS prophylaxis consisted of IT MTX+ARA-C+DXM given twice in cycles A and once in cycles B for a total of 8 doses.Results: 36 patients (17 HIV-negative and 19 HIV-positive) were included. Both groups of patients were comparable for age, gender, ECOG score, BM and CNS involvement, bulky disease, LDH and albumin serum levels. Fifteen patients had bone marrow infiltration of whom 3 reached ALL3 criteria. Four out of 19 HIV positive patients begun treatment with HAART at the time of diagnosis and 15 were already under treatment. Median follow-up was 1.7 years (range 0.8–4.1). Main results of therapy are summarized in table 1. No significant differences in CR, DFS or OS were observed between HIV-positive and negative patients. Grade 4 neutropenia and thrombocytopenia were almost constant and lasted a median of 7 and 5 days respectively (range 0 – 39). Other frequent grade 3–4 toxicities were hepatic (5% of cycles), mucositis (18%) and infectious (18%). Episodes of grade 3–4 extrahematological toxicity were more frequent in HIV-positive patients (77% of episodes of mucositis, p=0.04 and 72% of infections). Treatment delays >7 days due to toxicity of previous cycle were also more frequent in HIV-positive patients (41% vs 24%, p= 0.04). In conclusion, our results prove that the addition of rituximab to a specific BL/ALL3 treatment is also feasible and highly effective for HIV-positive patients with similar results to HIV- negative patients in terms of efficacy although with higher toxicity.Total (%) (n=36)HIV+ (%) (n=19)HIV- (%) (n=17)CR after two cycles30 (83)15 (79)15 (88)Toxic death (1st 2 cycles)5 (14)3 (16)2 (12)Resistance000Toxic death in CR2 (6)2 (11)0Relapses during treatment1 (3)01 (6)Relapses off treatment000Project. 1-year prob. DFS90%87%93%Project. 1-yr prob. OS78%73%82%