A Rare Case of Therapy Related Monoblastic Leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP Fusion and Hemophagocytosis

Abstract

Abstract Introduction/Objective Therapy related leukemias are often myeloid and occur as a late complication of cytotoxic therapy or radiotherapy. Most common etiologies are alkylating agents and topoisomerase II inhibitors leading to inaccurate base pairing and chromosomal breakages resulting in complex karyotypes. We describe an extremely rare case of therapy related monobalstic leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP Fusion and hemophagocytosis. Methods/Case Report An 81-year-old female with history of mixed cellularity Hodgkin’s lymphoma status post chemotherapy with AVD (Adriamycin, Vinblastine and Dacarbazine) and in remission presented with a complaint of newly developed skin rash on her chest. Punch biopsy showed a diffuse infiltrate of blastoid mononuclear cells with a component of monocytic differentiation present throughout the dermis. Complete blood count revealed bicytopenia (Hemoglobin 8.4 g/dl, platelets 32 x 109 per liter) and peripheral blood smear examination showed 54% blasts. Bone marrow biopsy was remarkable for infiltration by 79.2% blasts with monocytic differentiation and prominent hemophagocytosis. Immunophenotypic analysis was notable for weak positivity for p53 and a Ki67 proliferation index of 20%. These results led to the diagnosis of monobasic leukemia with hemophagocytosis. Cytogenetic analysis was abnormal with 19 out of 20 metaphases showing t(8;16)(p11.2;p13.3). Interestingly, FISH revealed the rare KAT6A- CREBBP fusion gene. The patient was hospitalized for induction chemotherapy and started on Decitabine. Her hospital course was complicated with acute kidney injury and pulmonary edema with rapid deterioration along with persistent elevation of blasts in the blood. The patient opted for hospice due to lack of improvement and died thereafter. Results (if a Case Study enter NA) NA. Conclusion AML with t(8,16) is an extremely rare entity accounting for 0.2 to 0.4% of AML cases. AML with t(8,16)/KAT6-CREBBP is frequently associated with monocytic or myelomonocytic differentiation, leukemia cutis and hemophagocytosis. While spontaneous remission can occur in a subset of neonatal t(8;16)(p11.2;p13.3), the majority of cases are therapy-related and carry a poor prognosis as seen in our patient.