Long-Term Outcome after Hyper-CVAD and Rituximab Chemoimmunotherapy for Burkitt (BL) or Burkitt-Like (BLL) Leukemia/Lymphoma and Mature B-Cell Acute Lymphocytic Leukemia (ALL).
Authors: Thomas Deborah A. , Kantarjian Hagop M. , Cortes Jorge , Faderl Stefan , Wierda William G. , Ravandi Farhad , Rodriguez Maria Alma , Fayad Luis , O’Brien Susan 
Published: April 2020

Abstract
The prognosis of BL, BLL and B-ALL has improved since 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 yrs and older [Thomas, JCO 17:2461, 1999]. Older age was also an adverse feature for relapse, with shorter 3-yr overall survival (OS) rates compared with younger pts (17% vs 77%). Since 1999, induction mortality has been reduced with use of laminar air flow rooms for elderly pts. Rituximab was also added (375 mg/m2 on days 1, 11 of hyper- CVAD and days 1, 8 of methotrexate/cytarabine courses for a total of 8 doses) for all pts. Two intrathecal treatments were given for CNS prophylaxis with each of the 8 courses. The initial report on 31 non-HIV pts treated with hyper-CVAD and rituximab showed encouraging results, with similar 3-yr OS rates (89% vs 88%) for elderly and younger pts [Thomas, Cancer, 106:1569, 2006]. Clinical benefit was also observed for HIV-positive pts treated with hyper-CVAD (with or without rituximab), if given concurrently with HAART therapy [Cortes, Cancer 94;1492, 2006]. Enrollment has continued. An update of the entire group of pts treated with the chemoimmunotherapy regimen was conducted. Forty-seven pts with newly diagnosed non-HIV BL (n=13), BLL (n=10), or B-ALL (n=24) were treated. Median age was 48 years (range, 17–77) with 25% aged 60 yrs or older. Advanced Ann Arbor stage III/IV was noted in &gt; 80% of cases. Fourteen HIV-positive pts with BL (n=8), BLL (n=1), or B-ALL (n=5) were also treated. The overall CR rate in 39 evaluable non-HIV pts (9 with CR at start either due to one course of prior therapy or resected disease) was 89%; 2 pts achieved partial response. All 11 pts aged 60 yrs or older achieved CR. One induction death was observed in the younger group. CR rate was 64% in the HIV-positive group (5 failures). After a median follow-up of 46 months (range, 3 – 93+ months) in the non-HIV group, 2 relapses were observed. Six pts died in CR related to infections (n=3) or unknown causes (n=2). For the non-HIV group, in comparison with 48 historical BL, BLL or B-ALL pts treated with hyper-CVAD alone, the 4-yr rates for OS (75% vs 50%, p=.04), age &lt; 60 yrs (76% vs 70%, p=.85) and age 60 yrs or older (72% vs 19%, p&lt;.01) were superior for hyper-CVAD with rituximab. 89% of non-HIV pts were beyond 1 yr of follow-up without disease recurrence. Toxicity profile was similar to hyper-CVAD alone. Three pts developed secondary neoplasms (acute myelogenous leukemia [AML] at 7 yrs, myelodysplastic syndrome at 3–1/2 years, AML with t(8;21) at 3 yrs). Rituximab improves long-term outcome when added to the hyper-CVAD regimen as frontline therapy of BL, BLL and B-ALL, particularly for elderly pts. User of newer anti-CD20 antibodies, such as ofatumumab, warrants investigation.