TREATMENT OF NEWLY-DIAGNOSED ACUTE PROMYELOCYTIC LEUKEMIA WITHOUT CYTARABINE

Purpose: To determine the effect of omission of cytarabine (ara-C) fro m treatment of newly diagnosed acute promyelocytic leukemia (APL), whi ch allows administration of more anthracycline. Patients and Methods: Induction consisted of all-trans retinoic acid (ATRA) 45 mg/m(2) daily until complete remission (CR) and idarubicin 12 mg/m(2) daily for 4 d ays beginning on day 5 of ATRA. patients in CR received two courses of idarubicin 12 mg/m(2) daily for 3 days and then, until 2 years post-C R date, alternated three cycles of mercaptopurine, vincristine, methot rexate, and prednisone (POMP) with one cycle of idarubicin 12 mg/m(2) daily for 2 days. Results in the 43 patients treated (41 with t(15;17) on standard or Southern analysis) were compared with those in 57 hist oric newly diagnosed APL patients given ara-C with either doxorubicin, amsacrine (AMSA), or daunorubicin without ATRA, using logistic and Co x regression to assess effects of non-treatment-related covariates on patient outcomes. Results: The CR rate in the current group was 77% (9 5% confidence interval [CI], 62% to 88%) and was not significantly dif ferent from the historic rate. In contrast, disease free survival (DFS ) in CR is superior in the current group (probability at 1 year 0.87; 95% CI, 0.73 to 1.0). This has translated into superior overall DFS fo r the current group (P = .03 adjusting for the predictive covariates i nitial WBC and platelet count; 1-year DFS probability 0.67; 95% CI, 0. 52 to 0.82; median follow-up 102 weeks). The current treatment appears better both in patients with and without t[15;17] on standard cytogen etic analysis. Conclusion: Given the difficulties inherent in comparin g sequential studies and recognizing the multiple differences in treat ment between current and historic groups, our results suggest that a l arge randomized trial incorporating use of ATRA should assess the util ity of omitting ara-C from treatment of newly diagnosed APL, thus allo wing delivery of more anthracycline. (C) 1997 by American Society of C linical Oncology.