Case presentation:
A 33-year-old healthy, non-smoker Bangladeshi gentleman presented with fatigue, subjective fever, bruises, and gum bleeding from 7 days without any significant weight loss or swellings on the body. He had no significant past medical history or any co-morbid illness.
Physical examination was remarkable for conjunctival pallor and few scattered patches of ecchymosis all over the body, with the largest measuring 3x2 cm over the abdomen. There were petechiae on the tongue and palpable spleen below the left costal margin. The rest of the systemic examination was normal. Initial blood investigations are shown in table:1.
Peripheral smear showed many circulating blasts cells (40%), few promonocytes, shift to left, and basophilia. Bone marrow aspirate showed many blasts (24%) with increased basophils, dwarf megakaryocytes, and significant dysgranulopoiesis, as shown in Figures 1, 2, and 3.
Flow cytometry on Bone Marrow aspirate showed a blast population with monocytic immunophenotype. FISH study revealed BCR/ABL-1 fusion gene in 95% of the cells. Karyotype analysis revealed, 46,XY,t(9;22;17)(q34;q11;q23)[2]/46,idem,t(3;21)(q26.2;q22)[28]/47,idem, t(3;21)(q26.2;q22),+8[25].
Overall findings were consistent with Acute Myeloid Leukemia with monocytic differentiation with features favoring evolvement on top of CML (blast phase), but another differential diagnosis of de novo AML with BCR/ABL-1 could not be excluded entirely during diagnostic workup. It was suggested initially to commence the patient on chemotherapy as per de novo AML protocol. However, after a thorough discussion with hemato-histopathologists and senior hematologists in a multi-disciplinary team (MDT) meeting, he was commenced earlier on TKI (Tyrosine kinase inhibitor therapy) as the majority of cells were suggestive of CML with BCR ABL fusion gene. Cytoreduction therapy with hydroxyurea and Dasatnib was started. He had a suboptimal response with an increase in blast cells after 3 weeks of therapy. It raised a concern about his diagnosis and reconsideration of de novo AML. Therefore, another MDT was held to review the patient clinical presentation and diagnostic workup. It concluded in favor of CML with evolution into acute myeloblastic phase with monocytic differentiation. As he was resistant to TKI therapy, mutation analysis for the T315I gene was sent to rationalize blast cells’ increase after Dasatinib therapy. Mutational analysis for the T315I gene turned out to be positive. Therefore, he was started on Ponatinib, a recommended TKI therapy for CML patients with a positive T315I gene. The drug was made available on special arrangements by a local hospital charity’s help due to its unavailability in the country. There was a good response with a decrease in WBCs, basophil cells, and blast cells in one week, as shown in Figures: 4.5 and 6, respectively. Further donor search was also initiated for hematopoietic stem cell transplant (HSCT), and he remained stable throughout his hospital course.