Comparison of Outcomes of Myeloablative Allogeneic Stem Cell Transplantation for Pediatric Patients with Bone Marrow Failure, Myelodysplastic Syndrome and Acute Myeloid Leukemia with and without Germline GATA2 Mutations.

Germline mutations in GATA2 are associated with an inherited predisposition to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation (HSCT) remains the only curative therapy. However, patients may be at an increased risk for transplant-related toxicity (TRT) and transplant-related mortality (TRM) due to their underlying disease biology. We performed a retrospective case-control study of pediatric patients with BMF/MDS/AML with germline GATA2 mutations, comparing HSCT outcomes to randomly selected patients without germline GATA2 mutations and BMF/MDS (control A) and acute leukemia (control B). The 5-year overall and disease-free survival rates in the GATA2 cohort (65%, 51%) were similar to control A (58%, 49%) and B (45%, 43%) cohorts. In contrast, the 5-year event-free survival rate was significantly lower in the GATA2 cohort (7% ± 6%, 28% ± 10%, and 33% ± 8% for GATA2, A, and B, respectively), due to an increased number of unique TRTs. Specifically, neurologic toxicities occurred significantly more frequently in GATA2 patients than in the control groups, and post-HSCT thrombotic events occurred only in the GATA2 cohort. There was no difference in TRM, infections, or graft-versus-host disease across groups. The higher incidence of thrombotic and neurologic events specific to GATA2 patients warrants further investigation and has potential treatment ramifications.