Impact of Induction Chemotherapy With Intermediate-Dosed Cytarabine and Subsequent Allogeneic Stem Cell Transplantation on the Outcome of High-Risk Acute Myeloid Leukemia

Abstract BackgroundAcute myeloid leukemia (AML) with antecedent hematological disease (s-AML) and treatment-related AML (t-AML) predict poor prognosis. Intensive treatment protocols of those highrisk patients should consider allogeneic stem cell transplantation (ASCT) in first complete remission (CR). Despite ASCT, relapse rate remains high. Induction chemotherapy with liposomal cytarabine and daunorubicin (CPX-351) has been approved for patients with AML with myeloid-related changes (AMLMRC) or t-AML based on improved survival and remission rates compared to standard 7+3 induction. Patients and Methods110 patients with newly diagnosed s-AML or t-AML at a university hospital were analyzed retrospectively. Median age was 62 years (24-77 years). A total of 65 patients with s-AML after MDS (59%) and 23 patients (20.9%) with t-AML were included. Induction chemotherapy consisted of intermediate-dosed cytarabine (ID-AraC) in combination with idarubicin (patients up to 60 years) or mitoxantrone (patients over 60 years). In patients subsequently undergoing ASCT reduced conditioning regimens (RIC) were applied prior to transplantation in 47 of 62 patients (76%). ResultsInduction chemotherapy with ID-AraC resulted in an overall response rate of 83% including complete remission (CR/CRi) in 69 patients (63%) with a low rate of early death (2.7%). Most relevant non-hematologic toxicity consisted of infectious complications including sepsis with need of intensive care treatment in five patients (4.5%) and proven or probable invasive fungal disease in 8 patients (7.2%). Relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) of the whole cohort were 19 months (0-167), 10 months (0-234) and 15 months (0-234), respectively (p<0.0001). A significant improvement of OS was observed in patients who underwent ASCT compared to those without subsequent ASCT: 9 months vs. 46 months, p<0.0001. Rate of transplantation-related mortality (TRM) in the early phase post ASCT was low (0.9% at day 30 and 1.8% at day 90, respectively). RIC conditioning results in OS rate of 60% after 60 months post ASCT (median OS not reached). ConclusionS-AML and t-AML patients receiving induction chemotherapy with intermediate-dosed cytarabine showed satisfactory response rate and consolidation therapy with ASCT after full or reduced intensity conditioning further improved survival in these patients with similar outcome as reported for CPX-351.