A Wolf in Sheep's clothing: Mastocytosis lurking under favorable risk AML

Systemic Mastocytosis associated with hematologic neoplasms (SM-AHN) is exceedingly rare in children posing diagnostic and therapeutic challenge. We report a 5-year-old girl with AML-M2 with RUNX1::RUNX1T1 and mutations in ASXL1 and NRAS. After first cycle of chemotherapy bone marrow was in complete remission but revealed the mast cell aggregates confirming SM-AHN. She had inadequate log reduction of RUNX1::RUNXITI fusion transcript and persisting mast cell aggregates even after 3 cycles of chemotherapy. Hence she was upstaged to high risk and underwent HLA haploidentical hematopoietic stem cell transplantation (HSCT). After two years from allogenic HSCT she remained in complete remission with 4.8-log reduction in RUNX1::RUNX1T1 fusion transcripts and complete clearance of mast cells. Identification of SM-AHN is crucial and allogeneic HSCT offers potential cure. Molecular detection of RUNXI::RUNXIT1 fusion transcripts is essential for monitoring therapy response, screening early relapse and pre-emptive therapeutic decisions. • Underlying Mast cells can be masked by the blasts at diagnosis of Acute Myeloid Leukemia that can be spotted out by detailed immunophenotyping • Early therapy intensification is mandatory in AML associated with Mastocytosis even when associated with good risk genetics • Following log reduction in real time PCR of RUNX1::RUNX1T1 fusion transcript helps identify response to therapy and early relapse.