Mds And Aml In Shwachman-Diamond Syndrome: Clinical Features And Outcomes

Genetic predisposition to MDS and AML is recognized in a growing subset of patients, but data to inform medical management and outcomes are sparse. Shwachman-Diamond syndrome (SDS) is an inherited marrow failure syndrome associated with increased risk of myelodysplasia (MDS) and acute myeloid leukemia (AML). The aim of this multi-institutional retrospective study was to investigate clinical features, treatment, and outcomes of 37 patients with SDS who developed MDS or AML. Diagnosis of SDS was established by SBDS genetic testing (n=30), exocrine pancreatic dysfunction (n=5), or data were unavailable (n=2). Nine individuals presented with AML (4 male, 5 female), 26 with MDS (13 male and 13 female), one male with refractory cytopenia (RC), and one male with isolated persistent somatic TP53 mutation. Eight of 26 MDS patients, had MDS-EB1 or EB2 at diagnosis, of whom two progressed to AML. Three patients initially presenting with early MDS progressed to MDS-EB1, MDS-EB2, or AML. Median age (years) at diagnosis of early MDS was 13.8 (range 0.5-28.8), for MDS-EB1/2 was 16 (range 9-30) and for AML was 33 (range 5.5-47). Nine patients with MDS and 1 patient with AML were receiving G-CSF chronically prior to diagnosis of MDS/AML.