Outcome after Frontline Therapy with the Modified Hyper-CVAD Regimen with or without Rituximab for De Novo Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL).

The hyper-CVAD regimen is an effective frontline program for de novo adult ALL and LL [

1. higher induction mortality in patients (pts) aged 60 years or older (17% vs 3%);

2. possible benefit of early anthracycline intensification;

3. worse survival with CD20 expression [Thomas D, Blood, e-pub]; and

4. late relapses after completion of POMP therapy.

Newly diagnosed or primary refractory (1 course only) pts with ALL (n=184) or LL (n=27) were treated on two sequential studies. Burkitt-type leukemia/lymphoma (BLL) and Philadelphia positive ALL were treated on alternative protocols. From May 2000 to December 2001, 69 pts were treated with the modified regimen as detailed above (9 courses of intensive chemotherapy). Course 2 was then eliminated from the regimen (8 courses of intensive chemotherapy), with an additional 145 pts treated to date. Median age was 40 yrs (range 15–83). CD20 expression was noted in 40%. Overall CR rate of the group (n=211) was 90%; 4 pts achieved PR, five failed to respond, and 3 died during the induction phase. After a median follow-up of 42 months (range, 2–80), outcome appeared favorable for the younger group (30 yrs or less) with 3-year remission duration (CRD) and survival (OS) rates of 70% and 80%. In the CD20 positive precursor B-cell ALL subset (n=88), rituximab improved outcome compared to historical experience, with 3-yr CRD rates (68% vs 28%, p<.001) and OS rates (65% vs 35%, p=.01) approaching those of the CD20 negative counterparts. In contrast to the Burkitt experience, rituximab was not beneficial for the elderly subgroup (OS rates 48% vs 35%, p NS). Anthracycline intensification appeared to worsen outcome. Rituximab appears to benefit the younger pts with CD20 positive precursor B-cell ALL. Incorporation of rituximab and other monoclonal antibodies (e.g., ofatumumab, epratuzumab) into frontline chemotherapy regimens should be investigated systematically.