Increased Incidence Of New-Onset Diabetes Mellitus Type Ii Following Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide For Sickle Cell Disease

Introduction: Haploidentical bone marrow transplant (haplo-BMT) with post-transplant cyclophosphamide (PTCy) provides near universal donor availability and curative potential for individuals with severe sickle cell disease (SCD). However, a recently recognized late-effect following allogeneic hematopoietic cell transplant is new-onset post-transplant diabetes mellitus type II (PTDM), which occurs in up to 50% of patients and is associated with a three-fold increase in mortality (Griffith et al BBMT 2011, Engelhardt et al BBMT 2019). Known risk factors for PTDM include older age, total body irradiation, and non-Caucasian ethnicity. Studies have shown that pre-transplant insulin resistance and enhanced immune cell alloreactivity are other important contributing factors (Engelhardt et al Blood 2011). To our knowledge, the incidence of PTDM following haplo-BMT with PTCy for SCD has not been characterized, in a population which is predominantly African-American, with a crude prevalence of diabetes mellitus type II of 16.4 (14.7-18.2), and thus represents an unmet need. We hypothesized that the ethnicity and chronic inflammatory state that exists in individuals with SCD contributes to an increased risk of PTDM and may be associated with worse transplant-related outcomes.