Comparison of Two Induction Regimens, High Dose Cytarabine /Mitoxantrone vs Hyper-CVAD, for Adult Acute Lymphoblastic Leukemia/Lymphoma.

Seventy-three consecutive adult patients with newly diagnosed ALL and lymphoblastic lymphoma were treated with either high-dose cytarabine /mitoxantrone (Ara-C/Mito) or Hyper-CVAD between January 1994 and January 2005 at the Westchester Medical Center. The regimens were chosen according to investigators’ preferences. The two induction regimens were either Ara-C 3 g/m²/d for 5 days and mitoxantrone 80 mg/m² on day 2 (52 patients) or Hyper-CVAD regimen (21 patients) containing four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate and Ara-C. All patients who were in CR received consolidation and maintenance therapy after induction. In Ara-C/Mito group, 45 (87%) of 52 patients achieved a complete remission (CR), 2 (4%) had resistant disease and 5 (9%) had died during remission induction in median follow-up of 48 months (range, 0.5 – 109 months). In Hyper-CVAD group, 16 (76%) of 21 patients achieved a CR, 4 (19%) had resistant disease and 1 (5%) had died during remission induction in median follow-up of 12months (range, 0.5 – 43 months). The difference of CR rate between the two groups was not statistically significant. (p=0.31). The overall survival (OS) of AraC/Mito group was 21 months (95% confidence interval [CI], 13 – 38 months), with a 3-year and 5-year OS of 36%, and 30%, respectively. In Hyper-CVAD group, OS was 26 months (95% CI, 26 -NR ), with a 3-year OS of 40%. The difference of OS between the two groups was not statistically significant (p=0.24). In Ara-C/Mito, median CR duration was 34 months (95% CI, 13-) and in Hyper-CVAD, median CR duration was not reached. In a combined multifactorial analysis of the two groups for prognostic factors, Age (<35) was the only favorable factor toward OS (p=0.03). Other prognostic factors including cytogenetics, cell type, WBC, LDH, were not statistically significant.

In conclusion: Ara-C/Mito and Hyper-CVAD appear to be comparable in terms of CR rate, toxic death, and OS in this single institution retrospective analysis. It will be interesting to compare the two induction regimens in a large multicenter randomized study.