Central nervous system relapse after allogeneic HCT in FLT3-mutated AML

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Central nervous system (CNS) relapse in acute myeloid leukemia (AML) is rare, but prognostically extremely unfavorable and associated with very high mortality rates. Aim of our single-center study was to define risk factors for CNS relapse in patients with FLT3-mutated AML after allogeneic hematopoietic cell transplantation (HCT) and to determine the impact of pre-emptive or salvage therapy with FLT3-inhibitors (FLT3i) on occurrence of CNS relapse and overall prognosis. We analyzed 39 FLT3-mutated AML patients who were treated with intensive induction therapy and consecutively underwent HCT at our institution. We observed that the remission status before HCT was strongly associated with relapse probability. Notably, FLT3-mutated AML showed a high propensity for CNS relapse with a cumulative incidence of 50% (95% confidence interval [CI], 16-77) at 2 years in non-responders pre-HCT compared to 0% in responders (cause-specific hazard ratio, 24.5, 95% CI, 2.9-206.2; p = 0.003). This was not abrogated by pre-emptive or salvage therapy with FLT3i in first relapse. Targeted therapies prior to transplant, use of intrathecal chemoprophylaxis or closer monitoring may be considered in patients with FLT3-mutated AML with active disease prior to HCT in order to prevent CNS relapse.

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