| BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid stem cell. The abnormal proliferation, differentiation and apoptosis of leukemia cells result in large numbers of cells accumulate in the bone marrow and other extramedullary tissues, which inhibit hematopoietic function of normal bone marrow and infiltrate in extramedullary tissues and organs.AML develops rapidly and the prognosis is poor, and induction therapy is the first step for all therapy options. At present the treatment of AML includes induction chemotherapy, post-remission (eg, consolidation) therapy and supportive treatment. Post-remission (eg, consolidation, strengthening) therapy is designed to eliminate minimal residual disease and to prevent disease recurrence. Patients can also undergo allo-HSCT in the consider of the condition. The main goal of induction chemotherapy is to achieve complete remission (CR) rapidly with minimal induction toxicity. According to the NCCN guidelines, anthracycline drugs sush as daunorubicin (DNR) or idarubicin (IDA) combined with standard dose cytarabine (Ara-C) ("3+7" regimen) act as first-line induction chemotherapy for adult patients with newly diagnosed acute myeloid leukemia (AML). Idarubicin (IDA) is derived from daunorubicin (DNR), and has been proved to be more effective than DNR because of the greater lipid solubility, long half-life and going through the blood-brain barrier.Therefore, we choose the IA regimen as induction chemotherapy for patients with newly diagnosed AML. In accordance with the NCCN guidelines, standard-dose idarubicin 10～12 mg/m 2 continuously infuse 3 days, with Ara C 100～200 mg/m 2 × 7 days during induction chemotherapy. Due to individual differences and patient tolerance, domestic IDA dose range from 6 to 12 mg/(m 2·d). However, if the effect of IDA increases with the dose is in controversial.ObjectiveThe purpose of this study was to investigate the clinical efficacy and toxicity and prognosis of different doses of IDA combined with Ara-c (IA) regimen in the treatment of AML (non APL) patients in Qilu Hospital of Shandong University and to explore an optimal dose for future clinical applications.MethodsFrom 2010 to 2015,83 adult AML (non APL) patients receiving IA regimen as induction chemotherapy in Qilu Hospital were retrospectively analyzed. Patients were divided into three arms according to the IDA dose, an IDA 10 mg/m2 arm, an IDA 8 mg/m2 arm and an IDA 6 mg/m2 arm. We compared the complete remission (CR) rate, hematologic side effects and long-term survival analysis among the three groups. The follow-up period was January 1,2010, to March 5,2016. Overall survival (OS), relapse-free survival (RFS) were recorded.Results(1) The first complete remission (CR) rate for 83 patients including 46 male and 37 female with an median age of 38 years after the first cycle of induction chemotherapy was 63.9% and overall remission (OR) rate was 77.1%. The complete remission (CR) rate after two courses of induction therapy was 73.5%.(2) CR rate in 10 mg/m2 Ida group was significantly higher than 8 mg/m2 and 6 mg/m2 Ida group after a course of treatment (88.2% vs 52.1%, p=0.016,88.2% vs 60.5%, p=0.037). OR rate in 10 mg/m2 Ida group was higher than the 8 mg/m2 and 6 mg/m2 Ida group (94.1% to 74.4%, p=0.086,94.1% to 69.6%, p=0.055). Total CR rate in 10 mg/m2 Ida group was significantly higher than 6mg/m2 Ida group (94.1% vs 60.8%, p=0.016). Total CR rate in 10 mg/m2 Ida group was higher than 8 mg/m2 Ida group (94.1% to 72.1%, p=0.062). The CR, OR, total CR were higher in the 8 mg/m2 Ida group than the 6 mg/m2 Ida group, but the difference was not statistical significance.(3) CR rate in 10 mg/m2 Ida group was higher than 8 mg/m2 and 6 mg/m2 Ida group, especially in the patients with high cytogenetics risk and FLT3-ITD positive mutation.(4) All patients presented cytopenias of grade Ⅲ-Ⅳ after chemotherapy. There was no differences in the recovery time of PLT≥20×109/L and ANC≥0.5×109/L after induction chemotherapy.(5) Within a median follow-up of 12 (2-55) months, the median OS for 6mg,8mg and 10mg group were 17,27 and 32 months, while the overall survival (OS) at 2 years were 37.5%,55.1% and 57.6% respectively and there was no significance among them as well as RFS.(6) Cox multivariate regression showed that without hematopoietic stem cell transplantation was an independent risk factor for the prognosis of OS and RFS.ConclusionsCompared with 8 mg/m2 and 6 mg/m2,10 mg/m2 IDA significantly improved the CR rate. Three groups were almost with the same extent of hematological side effects, and there was no significant difference in OS, RFS. COX multiple regression analysis showed that without hematopoietic stem cell transplantation was an independent risk factor for the prognosis of OS and RFS. |
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