CML-169: Myelomastocytic Blast Crisis in Chronic Myeloid Leukemia: Case Report

Myelomastocytic transformation in chronic myeloid leukemia blast phase (CML-BP) is an exceptionally rare phenomenon, characterized by coexpression of myeloid and mastocytic markers in leukemic blasts. This entity is defined by increased immature atypical mast cells (>10% metachromatic blasts) without fulfilling systemic mastocytosis criteria, notably lacking CD2/CD25 expression, D816V KIT mutation, and dense mast cell aggregates. This aggressive variant poses significant diagnostic challenges and is associated with poor outcomes, with only sparse cases reported in literature. To describe a rare case of CML-BP with myelomastocytic differentiation, emphasizing its distinct clinicopathological features, immunophenotypic profile, molecular landscape, and therapeutic response. A 45-year-old male with CML in chronic phase since 2016 progressed to blast crisis in 2025 following treatment discontinuation for over 5 years due to financial constraints. Bone marrow evaluation demonstrated hypercellularity with 30% blasts exhibiting dual myeloidmastocytic features. Morphologic analysis revealed metachromatic granulation in 50% of blasts, while immunohistochemistry showed strong CD117 and tryptase coexpression alongside CD34 + myeloblasts (8%–10%). Flow cytometry confirmed an aberrant immunophenotype with coexpression of myeloid markers (CD13/CD33/CD123) and bright CD117, along with CD7/CD4/CD9 aberrancy. Molecular profiling detected BCR::ABL1 (112% IS), a pathogenic RUNX1 frameshift mutation (38% VAF), and an ASXL1 variant of uncertain significance. Serum tryptase was normal, and D816V KIT mutation was absent. The patient achieved complete remission and major molecular response (MMR) following induction with 7 + 3 chemotherapy protocol (7 days of cytarabine and 3 days of idarubicin) combined with dasatinib. Allogeneic stem cell transplantation (allo-SCT) is now planned. This case illustrates a rare myelomastocytic transformation in CML-BP, emphasizing the critical role of integrated morphologic assessment, immunophenotyping, and molecular profiling for accurate diagnosis. While no established treatment guidelines exist for this rare entity, the observed complete remission following combined TKI and induction chemotherapy suggests that BCR::ABL1 -directed therapy remains effective despite clonal evolution and myeloid-mastocytic differentiation. Allo-SCT should be pursued when feasible, as it offers the best potential for long-term disease control. This report not only expands the clinicopathological spectrum of CML-BP but also highlights the necessity of comprehensive diagnostic approaches for rare leukemia variants to guide optimal therapeutic strategies.