Case Presentation: A 63-year-old female with a history of laryngeal cancer presented with upper abdominal pain, nausea, and fatigue. Labs showed a white blood cell count of 41.5 × 10^9/L, hemoglobin of 10.1 g/dL, platelet count of 162,000/µL, and absolute neutrophil count of 9.97 × 10^9/L, with basophilia (1.0 k/µL). Peripheral blood smear had circulating blasts (25% of cells) and abnormal megakaryocytes. Bone marrow biopsy revealed marked fibrosis and increased blasts with megakaryocytic morphology, exhibiting basophilic cytoplasm with blebbing. Flow cytometry confirmed Acute Myeloid Leukemia (AML).Following a provisional diagnosis of AML with megakaryocytic differentiation, induction chemotherapy with Cytarabine and Daunorubicin was started. Cytogenetic analysis later revealed Philadelphia chromosome, t(9;22)(q34;q11.2). PCR confirmed BCR-ABL1 fusion with p210 and a minor p190 component. Post induction therapy bone marrow biopsy showed persistent disease. Transitioning to Dasatinib, a tyrosine kinase inhibitor (TKI), resulted in significant clinical improvement.
Discussion: This case illustrates the diagnostic complexity in differentiating Chronic Myeloid Leukemia (CML) in blast crisis from de novo AML, especially in the absence of prior CML history. Although the histopathologic features favor a CML diagnosis, they may also be present in Ph-positive AML and Acute Lymphocytic Leukemia (ALL) [1]. This patient demonstrated both e13a2 and e14a2 (p210) and e1a2 (p190) transcripts. The initial management approach for suspected AML was justified by the clinical presentation and absence of previous CML documentation. However, CML blast crisis is typically more responsive to TKIs than conventional chemotherapy, suggesting that the use of a TKI as a primary therapy might have been a more targeted approach once cytogenetic and molecular data became available. TKIs are the established treatment for CML in blast crisis and Ph-positive ALL; however, their use in Ph-positive AML remains less well-studied. After starting Dasatinib, the patient achieved better disease control, supporting the effectiveness of TKI therapy in CML blast crisis.
Conclusions: This case emphasizes the importance of early and comprehensive diagnostic evaluations, including cytogenetic and molecular testing, to differentiate between CML blast crisis and de novo AML. An accurate diagnosis is crucial for guiding therapy, as inappropriate initial treatment with intensive chemotherapy can lead to unnecessary hospitalizations, increased adverse effects, and delayed initiation of effective targeted therapies. Integrating clinical, cytogenetic, and molecular data not only aids in accurate diagnosis but also facilitates timely treatment modifications, ultimately improving patient outcomes [2]. Baseline labs from prior facilities, if available, would have provided additional diagnostic context to guide early decision-making in this complex case.
