Baseline TP53 mutations in Adults with SCD developing Myeloid Malignancy following Hematopoietic Cell Transplantation

Sickle cell disease (SCD) is associated with severe morbidity and early mortality. Allogeneic hematopoietic cell transplantation (AlloHCT) is currently the only widely used curative therapy for SCD patients. While population-based studies report an increased incidence of hematologic malignancies in SCD patients, there is particular concern for an increased risk of development of myeloid malignancy following AlloHCT. Between September 2004 and April 2018 a total of 76 adult patients received an AlloHCT for SCD at the NIH Clinical Center. We report here on the three SCD patients who developed myeloid malignancy, all two to five years after unsuccessful nonmyeloablative allogeneic HCT. We show, in two cases, that TP53 mutations present at the time of post-transplant myeloid malignancy diagnosis were also detectable prior to transplantation and increased in frequency over time. Development of myeloid malignancy is a potential complication for SCD patients undergoing hematopoietic cell therapy and may be associated with detectable mutations prior to transplantation.