Clinicopathological characteristics and survival outcomes in adults with acute megakaryoblastic leukemia: A single-center retrospective analysis.

Abstract

e18525 Background: Acute megakaryoblastic leukemia (AMKL, AML-M7) is a rare, biologically heterogeneous type of Acute Myeloid Leukemia (AML) arising from megakaryoblasts, exhibiting surface antigens of megakaryocytic lineage. While AMKL in children with Down syndrome has relatively favorable prognosis, adults face significantly worse outcomes. Determinants of survival in adult AMKL remain poorly defined. Here, we report the clinco-genomic profile and treatment outcomes of patients with AMKL. Methods: We retrospectively reviewed patients aged ≥ 18 yrs with AMKL treated at our institution between 2012 - 2024. Demographic, molecular, and cytogenetic data, as well as treatment and survival outcomes were collected from medical records. Cytogenetic abnormalities were classified using European Leukemia Network (ELN) 2022 guidelines, and mutational profiling was done using next-generation sequencing. Overall survival (OS) was analyzed using Kaplan-Meier methods and log-rank test was used for comparison between subgroups. Results: 28 pts with AMKL were identified, of which 12 (42%) were newly diagnosed. The median age was 59.5 yrs and 50% were male. At diagnosis, the median WBC was 3.2x109/L (0.1–33), hemoglobin 8.5 g/dl (5.7–11.7), platelet count 41 x109/L (6–394), LDH 757 U/L (202 – 21225) and bone marrow blast percentage 26% (1–84). Antecedent hematologic disorders (AHD) were noted in 14%, and 32% had prior non-heme malignancies. Bone marrow fibrosis was present in 50%. Cytogenetics revealed complex karyotype (53%), del(5q) (35%), del(17p) (28%), and del(7q) (14%), with 78% classified as adverse risk. Common mutations were TET2 (57%), TP53 (53%), and EZH2 (17%), ASXL1 (14%), KIT (14%), KMT2A (14%), FLT3 (14%), NRAS (10%), JAK 2(10%). Venetoclax was used in 33% of pts in F/L and 50% in the salvage setting. Complete remission (CR) rate was 25% and 12% in pts with F/L and R/R AML, respectively, with a median OS of 17 and 49 weeks. Pts undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT; n=1 in F/L, 7 in R/R) had significantly better OS (70 vs. 17 weeks, p =0.0016) compared to chemotherapy alone. Elevated LDH >750 (median OS: 19 vs. 55 weeks, p=0.01) and AHD (median OS: 14 vs. 29 weeks, p=0.04) were associated with worse overall survival, while bone marrow fibrosis (p=0.07) and prior malignancies (p=0.06) showed borderline significance. Conclusions: Adult AMKL is a rare subset of AML, associated with resistance to conventional therapies, low rates of remission, and poor outcomes. This study underscores the potential benefit of allo-HSCT in improving OS. Markers such as elevated LDH and AHD emerged as significant predictors of poor outcomes. Notably, a third of pts with AMKL had history of a prior malignancy. These findings emphasize the need for novel therapies and a better understanding of disease biology to enhance survival in this high-risk population.