Medium-cumulative dose of cytarabine in consolidation therapy shows the greatest benefit in AML patients

Abstract

Background High-dose cytarabine (HDAC) is commonly used for consolidation therapy in young acute myeloid leukemia (AML) patients, but the dosage of cytarabine is still controversial in the clinic due to its obvious post-chemotherapy adverse effects. The aim of this study was to contrast the efficacy in different dose groups of cytarabine after consolidation therapy in Chinese AML patients. Methods AML patients treated with cytarabine consolidation at Qilu Hospital, Shandong University from January 2010 to September 2022 were retrospectively analyzed, from which 346 AML patients with relatively complete follow-up data were selected for this study. We compared the patients’ overall survival (OS) rate, relapse-free survival (RFS) rate, and hematologic adverse events in terms of their general characteristics, cytarabine consolidation therapy dose, consolidation course, 2022 European Leukemia Net (ELN) risk stratification, and transplantation. Results In AML patients under 60 years of age, the 5-year RFS rate with high-dose cytarabine consolidation therapy was superior to that of small-dose cytarabine (P = 0.024), while the 5-year RFS rate was comparable in the high-dose and intermediate-dose groups, and there was no obvious difference among the three groups in the 5-year OS rate (P > 0.05). OS and RFS of those given more than 3 courses of cytarabine consolidation therapy were better than those in the 1–2 courses group (P = 0.060, P = 0.040). OS and RFS were better in patients with cumulative dose of cytarabine ≥ 36g than in patients with cumulative dose < 36g (P < 0.05), but cumulative dose ≥ 54g was comparable in OS and RFS with ≥ 36–< 54g group (P > 0.05). There was no significant difference in hematologic adverse effects among the three treatment groups. In the latest ELN risk stratification favorable-risk group, the cumulative dose of cytarabine ≥ 36g had a better 5-year RFS rate than the < 36g group (P = 0.038), and in the intermediate-risk group the 5-year OS rate and RFS rate were better in the ≥ 36g group than the < 36g group (P = 0.012, 0.025). In addition, the prognosis of transplanted patients was better than that of non-transplanted patients, whereas in non-transplanted patients, consolidation therapy with ≥ 36g cytarabine can effectively improve outcomes. Multivariate analysis indicated that age, fibrinogen (FIB) and the cumulative dose of cytarabine of ≥ 36–< 54g were predictors of OS, while age, white blood cell (WBC) and HDAC were predictors of RFS. Conclusion The results of the study showed that consolidation therapy with cytarabine up to a cumulative dose of ≥ 36–< 54g in AML patients who did not undergo transplantation significantly improved patient prognosis. In the latest ELN risk stratification, cumulative doses of cytarabine ≥ 36g had a better prognosis in favorable and intermediate-risk patients.