Outcome with the Hyper-CVAD and Rituximab Regimen in Burkitt (BL) and Burkitt-Like (BLL) Leukemia/Lymphoma.

Abstract

Abstract The prognosis has improved for BL or BLL, particularly with use of short, intensive, multi-agent chemotherapy programs. Outcome of 26 non-HIV Burkitt leukemia patients (pts) treated with the intensive chemotherapy hyper-CVAD showed an overall CR rate of 81% with an induction mortality of 19% owing to systemic fungal infections in patients aged 60 years and older [Thomas et al, JCO 17:2461, 1999]. In addition, older age was an adverse feature predicting relapse with shorter 3-year overall survival compared with younger pts (17% versus 77%). Thus, the program was modified to give the induction course in laminar air flow rooms for pts aged 60 years or older. Given the high expression of CD20 in BL and BLL, rituximab was added to the regimen. From November 1999 to April 2004, 40 pts with newly diagnosed BL (n=28) or BLL (n=12) were enrolled. The median age was 47 years (range, 17–77 years) with 23% older than 60 years. Nine pts were HIV-positive. Advanced Ann Arbor stage III/IV was present in 80% (10% had CNS involvement). The median white blood cell count (WBC) was 8.3 x 109/L; 38% had WBC > 10 x 109/L. Rituximab was given at a standard dose of 375 mg/m2 days 1 and 11 of courses 1 and 3 with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) and days 1 and 8 of courses 2 and 4 with high dose methotrexate and ara-C. A total of 8 courses was planned along with 2 intrathecal prophylactic treatments of methotrexate and ara-C per course (total 16 intrathecals). The overall complete response rate in 22 evaluable non-HIV pts (2 too early, 7 with CR at start either due to one course of prior therapy or resected disease) was 95%, with no detectable difference between BL and BLL subtypes. No induction deaths were observed in the non-HIV group. After a median follow up of 18 months (range, 3 – 50+ months) in the non-HIV group, 2 relapses were observed. Six of 9 HIV pts achieved CR (2 resistant, 1 early death) but either died in CR of HIV-related infections (n=3) or relapsed (n=1), with 2 in continuous CR at 5 and 42+ months. Seventeen of the 31 non-HIV pts have been followed over one year from start of therapy without recurrence; one pt died in CR related to co-morbid conditions. Toxicity profile was similar to hyper-CVAD alone. Rituximab added to the hyper-CVAD regimen appears to improve outcome in BL and BLL.