Comparison of HiDAC Versus FLAG-IDA in the Treatment of Relapsed Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome

Background: Relapsed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) are associated with a poor prognosis. It is unknown which re-induction therapy provides the highest chance of durable remission. Commonly used therapies are high dose cytarabine (HiDAC) and triple therapy consisting of fludarabine, cytarabine, and idarubicin combined with granulocyte colony-stimulating factor (FLAG-IDA).

Methods: Two patient cohorts with relapsed AML or HR-MDS treated with HiDAC or FLAG-IDA between October 2015 and December 2021 in two academic hospitals in the Netherlands were retrospectively analyzed.

Results: Patients were treated with either HiDAC (n=22) or FLAG-IDA (n=25). Rates of CR (71% vs. 74%, P=0.85), 1-year OS (47% vs. 51%, P=0.99) and EFS (38% vs. 35%, P=0.71) were comparable between HiDAC and FLAG-IDA. Durations of neutropenia (median 24 days (IQR 20-26) vs. 30 days (IQR 22-39), P=0.014) and thrombocytopenia (22 days (IQR 17-26) vs. 36 days (IQR 26-53)) were significantly shorter in the HiDAC group than in the FLAG-IDA group.

Conclusion: While remission rates and survival outcomes were similar, FLAG-IDA was associated with longer periods of myelosuppression and transfusion dependency compared to HiDAC in these two cohorts. HiDAC can be considered as a salvage chemotherapyfor relapsed AML/HR-MDS based on our study.