Update of the Modified Hyper-CVAD Regimen in Newly Diagnosed Adult Acute Lymphocytic Leukemia (ALL). Session Type: Poster Session 494-III

Deborah A. Thomas, Jorge Cortes, Francis Giles, Susan OBrien, Stefan Faderl, Guillermo Garcia-Manero, Miloslav Beran, Charles Koller, Michael Andreeff, Steven Kornblau, Micheal Keating, Hagop Kantarjian

Author address: 

Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA; Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA


Hyper-CVAD is effective therapy for adult ALL [Kantarjian et al, JCO 18:547, 2000]. Intensive chemotherapy with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) was alternated with high dose methotrexate and ara-C every 21 days for 8 courses with G-CSF and prophylactic antibiotic support, followed by maintenance therapy with 6-MP, methotrexate, vincristine, and prednisone (POMP). Complete response (CR) rate with this program was 90%, and the 3-year disease-free survival (DFS) was 38%. A modified hyper-CVAD regimen was then developed to address the following issues: (1) higher induction mortality in patients (pts) aged 60 or older (17% versus 3%); (2) longer DFS reported with early anthracycline intensification, (3) worse survival with CD20 expression in ALL (excluding Burkitts [BL] and lymphoblastic [LL] subtypes), (4) CNS relapse rate of 6% and 1% in low and high risk pts, respectively, and (5) late relapses occuring after completion of therapy. Modifications to Hyper-CVAD Parameter Hyper-CVAD Modified Hyper-CVAD Laminar air flow rooms No For age 60 years or poor PS Dose-intensive anthracycline No C2 Lipo daunorubicin & ara-C Rituximab No For CD20 20% Intrathecal treatments 4-16 6-8 Maintenance (POMP) 2 years 3 years Intensifications (MTX, asparaginase) Months 7 & 11 Months 6,7 & 18,19 with hyper-CVAD From May 2000 to December 2001, 77 newly diagnosed or primary refractory (after 1 course only) pts were treated with the modified regimen. BL pts were excluded. Characteristics were median age 40 years (ranged 18-3) with 23% aged 60, and 56% males. Overall response rate was 98% (3 pts with lymphoblastic lymphoma had minimal residual mediastinal disease) with one induction death in a young construction worker with disseminated Aspergillus resulting in bowel perforation. Six of 18 pts (33%) aged 60 years died in CR versus 2 of 59 pts (3%), p<.001. deaths="" were="" related="" to="" pneumonia="" in="" and="" weeks="" sudden="" at="" failure="" thrive="" graft="" versus="" host="" disease="" after="" allogeneic="" transplant="" for="" philadelphia-positive="" all="" weeks.="" with="" a="" median="" follow-up="" of="" months="" dfs="" rate="" was="" overall="" wbc="" x="" two-year="" cd20="" treated="" rituximab="" compared="" negative="" p="0.04." anthracycline="" intensification="" the="" modified="" hyper-cvad="" regimen="" did="" not="" appear="" improve="" outcome="" group="" hyper-cvad.="" supportive="" care="" measures="" reduce="" induction="" mortality="" elderly.="" may="" longer="" is="" needed.="">

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Full conference title: 

American Society of Hematology 45th Annual Meeting
    • ASH 45th (2003)