Impact Of Conditioning Intensity And Genomics On Relapse After Allogeneic Transplantation For Patients With Myelodysplastic Syndrome

Myelodysplastic Syndrome (MDS) patients are at risk of relapse after allogeneic hematopoietic cell transplantation (alloHCT). The utility of ultra-deep genomic testing to predict, and the impact of conditioning intensity to prevent, MDS relapse are unknown. Targeted error-corrected DNA sequencing was performed on pre-conditioning blood samples from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0901 phase III randomized clinical trial which compared outcomes by alloHCT conditioning intensity in adult patients with less than 5% marrow myeloblasts and no leukemic myeloblasts in blood on morphological analysis at the time of pre-transplant assessment. Using a previously described set of 10 gene regions, 42% of patients had mutations detectable prior to randomization to reduced intensity or myeloablative conditioning. Testing positive was associated with increased rates of relapse and decreased overall survival. In those testing positive, relapse rates were higher and relapse-free survival was lower in reduced intensity versus myeloablative conditioning arms. Testing additional genes, including those associated with MDS, did not improve prognostication. This study provides evidence that post-transplant relapse rates in MDS patients are highest in those with pre-transplant genomic evidence of high-risk disease. In those testing positive, randomization to myeloablative conditioning lowered but did not eliminate relapse risk.