Recrudescence of a FLT3 wild-type CMML clone after allogeneic stem cell transplant for FLT3-ITD acute myeloid leukemia.

Late relapse after allogeneic hematopoietic cell transplantation (HCT) with phenotypic and molecular divergence from the original leukemia is rare. We describe a 60-year-old man with FLT3-ITD-mutated acute myeloid leukemia (AML) who achieved durable remission following venetoclax-based therapy and a combined HLA-matched sibling HCT-kidney transplant with FLT3 inhibitor maintenance. Four years post-transplant, he developed chronic myelomonocytic leukemia (CMML-1) characterized by re-emergence of driver mutations without FLT3-ITD, marked loss of donor myeloid chimerism, preserved donor T-cell chimerism, and sustained renal allograft function. This case highlights a unique clinical circumstance that may function to recontextualize myelomonocytic features in AML: that they can be attributed to acute leukemias arising from clonal hematopoiesis or occult chronic malignancies, as opposed to de novo AML, particularly given the difficulty in differentiating the two in the acute leukemic setting.