Pediatric Systemic Mastocytosis with t(8;21) AML and KIT D816V: Persistent Mastocytosis after Allogeneic Hematopoietic Cell Transplantation

Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) accompanied by t(8;21) acute myeloid leukemia (AML) is exceptionally rare in children, and its clinical course remains poorly defined.We report an 11-year-old girl with SM-AHN associated with t(8;21) AML and a KIT D816V mutation.At diagnosis, mast cells comprised 13.6% of bone marrow nucleated cells.Induction chemotherapy followed by salvage chemotherapy combined with midostaurin induced morphologic and cytogenetic remission of the leukemia, with a normal karyotype and negative RUNX1::RUNX1T1 fluorescence in situ hybridization; the marrow mast cell proportion nevertheless rose to a maximum of 86.0% and remained at 78.4% immediately before transplantation, accompanied by failure of neutrophil and platelet recovery.The patient underwent matched unrelated donor allogeneic hematopoietic cell transplantation (allo-HCT).Thereafter the leukemia remained in remission, with a progressive but incomplete decline in the RUNX1::RUNX1T1 transcript, a complete donor karyotype, and recovery of trilineage hematopoiesis.In contrast, CD25-positive spindle-shaped mast cells persisted at 40.2% of marrow nucleated cells on D+28 and 14.2% on D+97, and serum tryptase remained above the normal range throughout.The post-transplant course was complicated by steroid-refractory graft-versus-host disease, multiple opportunistic infections, Epstein-Barr virus-associated post-transplant lymphoproliferative disorder and multiorgan failure, and the patient died on D+158.This case demonstrates that leukemia-directed therapy, including intensive chemotherapy and allo-HCT, may induce and sustain leukemia remission while failing to eliminate the mast cell clone, underscoring the need for more effective mast cell-directed therapies in pediatric SM-AHN.