Project Details

Role of transferrin saturation in children undergoing bone marrow transplantation

Akhila Arcot Vadivelan, MBBS, FAAP

Summary

BACKGROUND: Pre-transplant iron overload is associated with increased rates of hepatic veno-occlusive disease (VOD) and inferior hematopoietic stem cell transplant (HSCT) outcomes and mortality. While pre-transplant chelation therapy is used to decrease iron overload before transplant, there is limited data about the use of peri-transplant chelation during conditioning chemotherapy GAP: There is limited data on effects of high toxic iron during peri transplant period. Chelation prior to transplant has been used with clear efficacy, but there is no data on the use of chelation to reduce toxic iron levels that are generated during conditioning in transplant when toxic iron levels are the highest. HYPOTHESIS: AIM 1: To determine longitudinal trend of transferrin saturation in children undergoing allogenic HSCT. Hypothesis: Transferrin saturation increases during conditioning and returns to baseline following erythroid recovery. AIM 2: To evaluate the relationship between transferrin saturation and markers of hepatic injury, cardiac injury, erythroid activity and engraftment. Hypothesis: Elevated transferrin saturation is associated with elevated transaminases, troponin, delayed engraftment and increased incidence of VOD, infections and graft vs host disease (GVHD) METHODS: Include children < 21 years of age undergoing HSCT with myeloablative conditioning. Exclude children with prior transaminitis (>3 times the upper limit of normal), abnormal renal function, cardiac disease in preceding 7 days to conditioning. Patients undergoing auto-transplant, non- myeloablative conditioning. We will obtain 2 mL of peripheral blood from the central line on specified days –4 to +21 to measure transferrin saturation and troponin-I. We will prospectively collect clinical correlates to these measurements including other lab parameters, imaging, and clinical outcomes like median time to neutrophil, platelet, and red cell engraftment, incidence of GVHD, VOD, relapse free survival, overall survival and 100-day mortality. RESULTS: Pending. IMPACT: This initial study will define how toxic iron levels change during HSCT and how they relate to organ injury, engraftment, and complications. The subsequent phases of the study will generate the first pediatric data on using iron chelation during conditioning, the period when iron toxicity peaks. Results will inform whether peri transplant chelation can reduce risks such as VOD, GVHD hepatitis, and infections. Safety and feasibility data will guide future larger trials of chelation during HSCT. Ultimately, this work aims to improve long-term survival in children. Website Link: https://som.cuanschutz.edu/Profiles/Faculty/Profile/39389