Anthracycline Dose Intensification in Adult Acute Lymphoblastic Leukemia: Lack of Benefit in the Context of the Fractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Regimen

Background: In previous studies of frontline therapy for adult acute lymphoblastic leukemia (ALL), early treatment with higher doses of anthracyclines has been reported to improve outcome. The current study was conducted to evaluate whether addition of anthracycline-based consolidation chemotherapy (Course 2) with liposomal daunorubicin (150 mg/m2 intravenously [IV] on Days 1 and 2) and cytarabine (1.5 g/m2 IV on Days 1 and 2) to the standard hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine) would improve outcome.

Methods: Sixty-eight consecutive adults with de novo ALL or lymphoblastic lymphoma were treated with this modified hyper-CVAD regimen inclusive of rituximab for CD20 expression≥20%.

Results: Sixty-three (93%) patients achieved complete response (CR). With a median follow-up of 90 months, the 5-year CR duration (CRD) and overall survival (OS) rates were 46% and 44%, respectively. Compared with 208 patients treated with standard hyper-CVAD (rates of 45% and 47%, respectively; P=not significant), outcome with the modified hyper-CVAD regimen was not improved overall. Outcome was improved by the addition of rituximab for the CD20-positive subset (rates of CRD and OS of 50% and 53%, respectively), whereas anthracycline intensification worsened outcome for the CD20-negative subset (rates of CRD and OS of 41% and 35%, respectively; P=.01) compared with standard hyper-CVAD. A high mortality rate related to infections in CR was noted among patients aged 60 years or older.

Conclusions: In the context of the hyper-CVAD regimen, early anthracycline intensification did not improve outcome for adults with de novo ALL or lymphoblastic lymphoma.