From crisis to cure Allogeneic stem cell transplantation for adults with sickle cell disease

Sickle cell disease (SCD) is a group of inherited hemoglobinopathies, associated with chronic hemolytic anemia, recurrent vaso-occlusive pain episodes, and progressive organ damage. To date, allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative treatment for patients with SCD. Historically, HSCT was used in children with severe SCD and an available matched sibling donor, applying myeloablative conditioning regimens. More recently, non-myeloablative conditioning and haploidentical HSCT protocols have been developed, rendering HSCT a feasible treatment option for many more patients, including adult patients with SCD. In the Netherlands, the first non-myeloablative transplantation program for adult patients with SCD was implemented in 2018 at the Amsterdam UMC. The studies presented in part I of this thesis aim to improve the outcomes after non-myeloablative HSCT in adult patients with SCD, with a focus on reducing graft failure rate while balancing the toxicity of the conditioning regimen and the risk of GvHD. In part II of this thesis, three studies are presented which sought to enhance our understanding of the impact of allogeneic HSCT on the patients’ immune system. Last, part III of this thesis focusses on evaluating the effects of HSCT on SCD-related organ (dys)function and health-related quality of life.