Abstract
Early studies report extremely poor outcome in AIDS-related Burkitt’s lymphoma treated with standard dose chemotherapy. This poor prognosis is not improved by Highly Active Antiretroviral Therapy (HAART). 53 patients with HIV infection and stage IV Burkitt lymphoma/leukemia (BL) participated a unicentric and prospective clinical trial to evaluate the safety and efficacy of the intensive LMB-86 chemotherapy regimen. The median CD4 cell count was 236 x 106/l. 32 tumors were of the Burkitt type and 21 were Burkitt-like. All patients had stage IV disease with bone marrow involvement in 40 and central nervous system disease in 37. The LMB-86 regimen combined: (1) cytoreductive phase, with low dose cyclophosphamide, vincristine and steroids; (2) induction phase, with 2 consecutive courses of COPADM with high dose (8 g/m2) methotrexate (MTX); (3) consolidation phase with two courses of CYVE with high dose cytarabine and etoposide; (4) maintenance phase, with four courses combining previous drugs with lower dosage.
Thirty eight patients (71.7 %) achieved complete remission after the induction phase. With a median follow-up of 74.1 months (range, 8–153.1), 11 have progressed on therapy or relapsed. The median survival was 14.2 months and 32 patients have died. Most of deaths were due to BL (n=17, 53.1%), 5 (15.6%) to treatment toxicity, 7 (21.9%) to AIDS and 3 (9.4%) to other causes. The 1-year and 2-year estimate survival were 51% (95% CI, 44.1%–57.9%) and 47% (95% CI, 40.1%–53.9%), respectively (figure). Median disease free survival (DFS) was 41.7 months (range, 11.5-not reached) with a 2-year estimate DFS of 59.3%. Using the univariate analysis, four baseline covariates were associated with shorter survival: CD4<200 x 106/L (HR 3.3; 95% IC, 1.6–6.6), CD8 <1500 x 106/L (HR 2.5; 95% IC, 1.1–10), "B" symptoms (HR 3.6; 95% IC, 1.1–11.9), and ECOG score > 2 (HR 2.9, 95% IC, 1.3–6.4). No other HIV covariates, lymphoma baseline data or demographic data were associated with outcome. Using multivariate analysis only association with low CD4 count was significant (p=0.03).
Intensive chemotherapy regimen (LMB-86) containing high dose MTX and cytarabine is highly efficient in stage IV AIDS-related Burkitt’s lymphoma. Toxicity is high but acceptable with regard to the best overall survival reported to date.
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