A 16-year-old boy presented with marked leukocytosis (117.1 × 103/μL) and thrombocytopenia (47 × 103/μL). Peripheral smear showed 90% blasts (panels A-C; 100× objective, total magnification ×1000; Wright-Giemsa stain) that showed frequent azurophilic granules (red arrows), occasional pseudo-Chédiak-Higashi granules (yellow arrow), and rare Auer rods (green arrow). Flow cytometry revealed a mixed T/myeloid phenotype (panel D), ie, positivity for CD45 (dim), CD34, CD117, CD13, CD33 (dim), HLA-DR, cytoplasmic-myeloperoxidase (MPO) (subset, black arrow), cytoplasmic-CD3, CD2, CD5 (dim/partial), CD7, and CD56; and negativity for CD14, CD64, surface-CD3, CD16, CD4, CD8, and TDT. Bone marrow biopsy showed sheets of blasts positive for CD3, MPO (focal), and CD34 by immunohistochemistry. Cytogenetics showed a normal male karyotype. Comprehensive fluorescence in situ hybridization panels for pediatric acute myeloid leukemia and T-acute lymphoblastic leukemia were negative for all probes tested, including BCR::ABL1 and PML/RARA fusions, and KMT2A rearrangement. A 47-gene next-generation sequencing panel detected an isolated FLT3-ITD mutation. A diagnosis of mixed phenotypic acute leukemia (MPAL) T/myeloid, not otherwise specified was rendered, and induction therapy per AALL1732 protocol (mBFM+ inotuzumab ozogamicin) and gilteritinib were administered. Postinduction marrow biopsy showed no evidence of residual disease by minimal residual disease flow cytometric evaluation and FLT3-ITD reverse transcription-polymerase chain reaction mutational analysis was negative.
Pathogenic FLT3 mutations have been reported in a subset of MPALs and present a potentially beneficial therapeutic target as well as a viable option for residual disease monitoring.
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