A Randomized Comparison of Modified Intermediate-dose Ara-C versus High-dose Ara-C in Post-remission Therapy for Acute Myeloid Leukemia

Background: We conducted a prospective, multicenter cooperative study to compare two courses of modified intermediate-dose cytarabine (Ara-C) (mIDAC; Ara-C at a dose of 1.0 g/m(2) every 12 hours for 5 days) versus high-dose Ara-C (HDAC; Ara-C at a dose of 2.0 g/m(2) every 12 hours for 5 days) in post-remission therapy for acute myeloid leukemia (AML) to confirm the post-remission antileukemic efficacy and safety of mIDAC. Patients and Methods: Twenty-six newly diagnosed patients with AML underwent remission induction therapy consisted of behenoyl Ara-C, mitoxantrone, etoposide, and 6-mercaptopurine. Post-remission therapy included four courses of consolidation and four courses of intensification. Patients who achieved complete remission (CR) were randomly assigned to mIDAC or HDAC for the second course of consolidation. The third course of intensification was the same as the second course of consolidation. Other post-remission therapies were the same in each group. Results: Twenty-two patients (84.6%) achieved CR and 21 patients were randomly assigned to receive either mIDAC (n=11) or HDAC (n=10). The predicted 4-year relapse-free survival for the mIDAC group and for the HDAC group were 49% and 56%, respectively (p=0.86). Although HDAC developed severe leukocytopenia compared to mIDAC, there were no significant differences between HDAC and mIDAC in the incidence of >= grade 3 and >= grade 4 documented infections. The mean lowest white blood cell count (WBC) after HDAC was significantly lower than that after mIDAC (0.208 +/- 0.120 x 10(3)/mm(3) and 0.459 +/- 0.333 x 10(3)/mm(3), respectively, p<0.05). The time to WBC recovery to 2.0 x 10(3)/mm(3) after HDAC was significantly longer than that after mIDAC (34.3 +/- 12.1 days and 27.1 +/- 9.5 days, respectively, p<0.05). Conclusion: This study suggests that mIDAC may have an equivalent post-remission antileukemic efficacy to HDAC with less myelosuppression for AML patients.