Goal-oriented monitoring of cyclosporine is effective for graft-versus-host disease prevention after Hematopoietic Stem Cell Transplantation in Sickle Cell Disease and Thalassemia major

Abstract Graft-versus-host disease (GvHD) is an important challenge and one of the major causes of morbidity and mortality in children after hematopoietic stem cell transplantation (HSCT). Herein, we report our institution's experience of a goal-oriented Bayesian monitoring for cyclosporine (CsA) used alone as GvHD prophylaxis during the post-transplant period in pediatric patients with Thalassemia Major (TM) or Sickle Cell Anemia (SCA) undergoing HLA-matched HSCT. We also studied evolution of chimerism. Twenty-six consecutive patients (14 SCA; 12 TM) underwent matched sibling donor (MSD) HSCT from 2004 to 2014. All patients received a myeloablative conditioning regimen. GvHD prophylaxis consisted of 20 mg/kg of antithymocyte globuline (ATG) in conditioning regimens then CsA alone in the post-transplant period. Target CsA trough blood concentration (TBC) was 150 +/- 20 ng/ml. At last follow-up, all patients are alive and free of disease, even in case of mixed chimerism. Engraftment occurred in all patients. No patient developed grade II-IV acute GvHD, 4 patients developed acute grade I skin GvHD and only one presented with chronic pulmonary GvHD. A better control of GvHD and immunosuppression by a strict monitoring of CsA TBC as described herein is promising and could play a crucial role. Further investigations are required but this study opens new perspectives to improve survival and safety of HSCT from alternative donors in TM and SCA to levels compatible to that obtained with matched-sibling donors.