高三尖杉酯碱、阿糖胞苷、柔红霉素或去甲氧柔红霉素(HAD/HAI)诱导治疗初治急性髓系白血病的长期疗效分析

OBJECTIVE: To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML). METHODS: The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated. RESULTS: Of 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1–104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup. CONCLUSION: HAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.