AML-336 M5b AML With t(8;16) (p11.2; p13.3) KAT6A/CREBBP Fusion and FLT3-TKD Mutation: Analysis of Mitelman Database

Abstract

t(8;16) (p11.2; p13.3)/KAT6A-CREBBP fusion is a rare cytogenetic abnormality usually associated with treatment-related AML (t-AML) that usually exhibits unique characteristics while accounting for <0.5% cases of AML and being more common in female patients. Reported overall survival (OS) in these patients is poor and varies from 4.7 to 18.2 months. Patients with de novo AML with t(8;16) or t-AML with t(8;16) without adverse prognostic factors (e.g., complex karyotype) have a good outcome. We present a case of AML with a rare translocation abnormality, t(8;16), which is usually associated with cytotoxic therapies, but there was no prior history in our patient. The translocation results in KAT6A/CREBBP fusion. Immunophenotyping revealed expected myeloid and monocytic markers with CD45 (dim), cMPO, CD56 (partial), CD71, and CD38. The patient was started on a 7+3 induction regimen with cytarabine and daunorubicin. Midostaurin was added due to FLT3-TKD mutation. She was found to be disease free on a follow-up marrow biopsy, and she received a single cycle of HiDAC for maintenance. On a subsequent visit, she was found to have relapsed, so a second-line therapy with FLAG-IDA was considered. Day 17 bone marrow biopsy was performed with no flow cytometric evidence of leukemic cells, with a CR+MRD negative status, so she was discharged with follow-up at the BMT clinic for allogeneic stem cell transplant. KAT6A and CREBBP genes produce transcripts that are involved in histone acetylation. It is unknown whether the chimeric fusion gene produces a functional transcript that could contribute to leukemogenesis. Our Mitelman database analysis reveals only 175 reported cases; furthermore, this is the first patient who had an FLT3-TKD mutation. A vast majority of these are either M4 or M5 types (132/175, 75.4%). OS is poor, ranging from 4.7 to 18.2 months. This AML type exhibits unique characteristics such as hemophagocytosis, DIC, leukemia cutis, and monoblastic or myelomonocytic differentiation. Mitelman database analysis reveals that a vast majority of cases with t(8;16) are either M4 or M5 AML. Careful consideration of treatment options would be recommended based on age as chromosomal abnormalities play a major role in prognosis, especially with t(8;16).