The primary objective is to implement a personalized approach to curative therapies for children and adults with sickle cell disease (SCD) to maximize benefits while minimizing adverse outcomes. Current efforts to understand long-term health outcomes after these therapies are limited. The focus on initial treatment success recalls developments in pediatric oncology during the 1980s, where effective therapies eventually led to increased risks of organ dysfunction and malignancies.
As new treatments for SCD, such as allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy, emerge, studying their long-term health effects becomes crucial for personalized care. Unfortunately, adverse outcomes, such as therapy-related myeloid neoplasms and clonal hematopoiesis of indeterminate potential (CHIP), have begun to appear. Notably, 10% of deaths following HSCT occur more than five years after the procedure.
In a multicenter retrospective-prospective cohort study, the researchers will test the following hypotheses:
- Myeloablative therapies in children will lead to increased pulmonary and renal dysfunction compared to standard therapy;
- Nonmyeloablative HSCT in adults will not significantly affect FEV1% predicted but will accelerate eGFR decline compared to standard therapy;
- Nonmyeloablative HSCT will improve TRJV in adults with SCD; and 4) Both nonmyeloablative allo-HSCT and myeloablative gene editing will cause post-HSCT therapy-related myeloid neoplasms.
NIH Grant 5U01HL156620