Mixed Phenotypic Acute Leukemia Transformation in a Patient with Chronic Myeloid Leukemia: A Rare Case of Blast Crisis

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR::ABL1 fusion gene and uncontrolled granulocyte proliferation.¹ CML typically progresses through chronic, accelerated, and blast phases.² Blast crisis, the terminal phase, resembles acute leukemia and usually manifests with myeloid or lymphoid blasts; transformation into mixed phenotypic acute leukemia (MPAL) is exceedingly rare.³

A 31-year-old male with chronic-phase CML on imatinib presented with a one-week history of painless left cervical lymphadenopathy, low-grade fever, and night sweats. Examination revealed firm, non-tender cervical nodes without hepatosplenomegaly. Laboratory evaluation showed leukocytosis (57,730/µL), anemia (Hb 10.8 g/dL), thrombocytopenia (90,000/µL), and 82% peripheral blood blasts. Bone marrow aspiration demonstrated 91% blasts (Figure 1; Figure 2), and lymph node biopsy revealed diffuse blast infiltration.

Flow cytometry confirmed MPAL of myeloid/T lineage: blasts expressed cyCD3, CD2, CD7, CD34, CD117, CD13, CD33, HLA-DR, and dim MPO, with negative B-lineage markers (Figure 3). Cytochemical MPO staining was positive in >3% of blasts.

The patient received FLAG-IDA chemotherapy for five days with supportive G-CSF, antimicrobials, and transfusions. Asciminib 40 mg twice daily was initiated on Day 21. MRD assessment on Day 28 post-chemotherapy showed no residual T-lineage disease (<0.01%) and low-level residual myeloid blasts (1.31%). The patient was discharged in stable condition and referred for allogeneic stem cell transplantation.

CML progression to MPAL is rare, with only isolated adult cases reported. Diagnosis requires comprehensive immunophenotyping; co-expression of cyCD3 and MPO fulfills WHO criteria for MPAL, myeloid/T lineage.⁴ Extramedullary involvement, such as lymphadenopathy, supports blast phase transformation. Blast crisis pathogenesis involves clonal evolution, genetic instability, additional cytogenetic abnormalities, and BCR::ABL1 mutations contributing to TKI resistance.⁵ Intensive chemotherapy with TKI consolidation and allogeneic stem cell transplantation remains the mainstay of treatment.¹ FLAG-IDA followed by asciminib in this patient led to clearance of T-lineage blasts, highlighting lineage-specific therapeutic response and the aggressive, heterogeneous nature of MPAL.

MPAL arising as CML blast crisis is a rare and aggressive entity requiring high clinical suspicion. Comprehensive immunophenotypic, cytogenetic, and molecular evaluation is essential for timely diagnosis. Early recognition and appropriate therapy, including consideration of stem cell transplantation, can influence outcomes in this high-risk condition.