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.