Clonally Distinct FLT3-TKD Mutations in Host and Donor-Derived AML After Double Cord Blood Transplant: A Case Report

Donor-derived leukemia (DDL) is a rare complication of hematopoietic cell transplantation with poorly understood mechanisms. We report a case of DDL arising 1 year after double cord blood transplant for AML. The secondary leukemia demonstrated a distinct immunophenotype, donor origin, and novel mutations (FLT3 D835E, NPM1, NRAS) absent in the primary disease. Notably, both leukemias harbored distinct FLT3-TKD mutations, suggesting convergent evolution despite separate clonal origins. Absence of pathogenic variants in the cord blood supports de novo leukemogenesis. These findings implicate host or microenvironmental factors in driving leukemic transformation and highlight potential shared selective pressures in FLT3-TKD mutant AML.