# Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia Patients Have Dismal Outcomes Irrespective of Allogeneic Hematopoietic Stem Cell Transplant: A Single-Center Experience

## TL;DR

Pediatric non-Down syndrome acute megakaryoblastic leukemia has very poor survival rates, even after stem cell transplants, highlighting the need for new treatments.

## Contribution

This study provides insights into the poor outcomes of non-DS-AMKL patients and suggests the need for novel therapies.

## Key findings

- Non-DS-AMKL patients have a 5-year overall survival rate of 19.1%.
- Relapse is the main cause of death, with a 78% cumulative incidence of relapse.
- Allogeneic stem cell transplant did not improve survival outcomes in these patients.

## Abstract

Pediatric acute myeloid leukemia (AML) is a challenging disease to treat. Patients with relapsed or refractory disease have poor overall survival outcomes despite aggressive chemotherapy and hematopoietic stem cell transplant. This is particularly true for non-Down syndrome patients with an aggressive subclassification of AML: acute megakaryoblastic leukemia (AMKL). While only comprising a fraction of total pediatric AML diagnoses, this disease subtype has among the highest mortality rates. Our research sought to identify trends in the outcomes at a single, large, tertiary care hospital. Outcomes were suboptimal despite the use of allogeneic stem cell transplantation in first remission, with disease relapse being the main cause of mortality in our cohort. Results from this study demonstrate the need for continued research on novel drug development designed to treat this high-risk subtype, with expedient translation to the bedside.

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1). Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort. Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children’s Hospital from 2000 to 2022 was conducted. Results: Twenty-nine patients were included in the analysis, with cohorts defined by intention to treat. Twelve patients received chemotherapy only during upfront therapy, and seventeen received upfront HSCT. The 5-year overall survival (OS) and disease-free survival (DFS) for the entire cohort were 19.1% and 24.1%, respectively, with a median survival of 17.4 months. A higher percentage of patients in the chemotherapy-only group had relapsed/refractory disease at death (chemotherapy only, n = 9; HSCT, n = 8). However, 5-year OS and DFS were similar for both groups (OS = 18.8% vs. 31.3%, p = 0.58; DFS = 37.6% vs. 22.2%, p = 0.51). Relapse was the leading cause of death (5-year cumulative incidence of relapse (CIR) 0.78). Treatment with allo-HSCT did not improve outcomes due to the high CIR, even after HSCT in CR1. Conclusions: These dismal outcomes highlight the need for development and incorporation of novel targeted agents into upfront therapy or in the post-HSCT setting for patients with this challenging disease.