Outcome after Detection of Minimal Residual Disease during Treatment with the Modified Hyper-CVAD Regimen with or without Rituximab in Newly Diagnosed Adult Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL).

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

Newly diagnosed ALL or LL pts were treated on two sequential studies. BL and Ph-ALL pts were treated with other hyper-CVAD regimens. From May 2000 to December 2001, 69 pts received the modified regimen as above (9 courses of intensive therapy). Course 2 was eliminated from the second study, with an additional 113 pts treated (8 courses of intensive therapy). The median age for these 182 pts was 39 years (range, 15–83); 19% were ≥ 60 years old and 57% were males. Overall response rate was 90% (6 too early); 96% for the CD20+ group vs 86% for the CD20− group (p=.0.02). Induction mortality was 2%. The addition of rituximab for the CD20+ subgroup appeared to improve DFS compared with hyper-CVAD alone (83% vs 50%, p=.018), but not survival (OS) (72% vs 66%, p=0.327). The 2-yr OS rate for the elderly group was 22% vs 79% for their younger counterparts (p<0.001). In the latter study, minimal residual disease (MRD) was assessed by multiparameter flow cytometry (FC) at the time of CR as feasible. IgH by PCR, T-cell receptor (TCR) gamma and beta gene rearrangements by Southern or PCR, and cytogenetics (with FISH for 11q23 or others) were repeated if abnormal at diagnosis. TCR rearrangements were seen in 70% of pts with pre-B or CALLA immunophenotype. Of 83 evaluable pts, 20 (24%) were positive for MRD by FC at CR; 2-year DFS and OS rates were inferior compared with those negative for MRD by FC (58% vs 84%, p=0.02; 53% vs 73%, p=0.057). Alternative therapeutic strategies will be developed for the elderly pts and those with detectable MRD by FC at CR. Additional analysis of the latter subgroup, the other measures of MRD, and impact of MRD on outcome will be forthcoming.