Prognosis has improved for BL, BLL and B-ALL with the advent of short, intensive, multi-agent chemotherapy regimens. A complete remission (CR) rate of 81% in 26 non-HIV patients (pts) with B-ALL treated with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine) was influenced by an induction mortality of 19% related to systemic fungal infections in pts aged 60 years and older [
Thomas, JCO 17:2461, 1999
]. Older age was also an adverse feature for relapse, with shorter 3-year overall survival (OS) compared with younger pts (17% versus 77%). Thus, the program was modified in 1999 to administer the induction course in laminar air flow rooms for elderly pts with incorporation of rituximab for all pts. Our initial report of 31 non-HIV pts showed encouraging results with similar 3-year OS rates (89% versus 88%) for the elderly and younger pts treated with hyper-CVAD and rituximab [Thomas, Cancer, 106:1569, 2006
]. Clinical benefit was also observed for HIV-positive pts with BL or BLL after hyper-CVAD with or without rituximab if given concurrently with active HAART therapy [Cortes, Cancer 94;1492, 2006
]. An update of the entire group of pts treated with the chemoimmunotherapy regimen was conducted. Forty-four pts with newly diagnosed non-HIV BL (n=12), BLL (n=10), or B-ALL (n=22) were treated. Median age was 46 years (range, 17–77) with 23% aged 60 years or older. Advanced Ann Arbor stage III/IV was present > 80% of cases. Thirteen HIV positive pts with BL (n=7), BLL (n=1), or B-ALL (n=5) were also treated. Rituximab 375 mg/m2 was given on days 1 and 11 of hyper-CVAD and on days 1 and 8 of methotrexate and cytarabine for a total of 8 doses. Pts received 8 cycles of therapy as feasible, with 2 intrathecal treatments per course for CNS prophylaxis. The overall CR rate in 38 evaluable non-HIV pts (6 with CR at start either due to one course of prior therapy or resected disease) was 89%; 2 pts achieved partial response. All 10 pts aged 60 years or older achieved CR. One induction death was observed in the younger group. CR rate was 61% in the HIV group, with 5 failures. After a median follow up of 33 months (range, 4 – 83+ months) in the non-HIV group, 2 relapses were observed. Five pts died in CR related to infections (n=3) or unknown causes (n=2). For the non-HIV group, comparison with 44 historical BL, BLL or B-ALL pts treated with hyper-CVAD alone, the 3-yr rates for survival overall (80% vs 50%, p=.04), age < 60 years (80% vs 70%, p=.59) and age 60 years or older (80% vs 19%, p<.01) were superior for hyper-CVAD and rituximab. Toxicity profile was similar to hyper-CVAD alone; 2 pts developed secondary neoplasms (acute myelogenous leukemia at 7 years, myelodysplastic syndrome at 3–1/2 years). Rituximab appears to improve long-term outcome when added to the hyper-CVAD regimen for frontline therapy of BL, BLL and B-ALL, particularly for elderly pts.
Disclosure:Consultancy: LF, AR, SOB for Genentech, Inc. Research Funding: DAT, SF, WW, AR, LF, SOB from Genentech, Inc. Honoraria Information: DAT, SF, WW, AR, LF, SOB from Genentech, Inc. Membership Information: DAT, SF, WW, AR, LF, SOB for Genentech, Inc. Off Label Use: Ritixumab for newly diagnosed Burkitt-type leukemia/lymphoma.
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