ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HCT) IN CHILDREN AND ADOLESCENTS WITH SICKLE CELL DISEASE (SCD): A FEASIBLE CURATIVE OPTION WITH HLA-IDENTICAL OR HAPLOIDENTICAL DONORS

Abstract

Introduction: HCT is the only curative option available in Brazil to SCD. Most patients do not have an unaffected Matched Sibling Donor (MSD), so alternative donor options are urgently needed. The Vanderbilt Global Haploidentical Learning Collaborative (VGC2) has led an international initiative to develop haploidentical HCT for SCD. Due to the 43% rejection rate with the original Hopkins protocol (Bolaños-Meade, 2012), Thiotepa (TT) was added with excellent results in adults, but 30% rejection in children (Kassim, 2024) despite marrow suppression with hypertransfusions and hydroxyurea. Objective: This paper is to report the experience of HCT in children and adolescents with SCD, comparing outcomes with MSD, haploidentical HCT as initially transplanted (Haplo) and Haplo with augmented conditioning therapy (AugHaplo). Methods: Conditioning therapy for MSD was (total doses) ATG 4.5 mg/kg, busulfan AUC 4.500 day, fludarabine (Flu) 120 mg/m2 and Cy 200 mg/kg, erythrocytheresis at admission to lower HbS 90% chimerism. Immunosuppression was suspended in 36% and is being reduced in 21%. 16% had III‒IV acute GVHD and 27% chronic GVHD, none severe. All patients had viral reactivations, mostly CMV and HHV6. Other complications in 1 patient each were Guillan-Barre syndrome, PRES, interstitial pneumonia and alveolar proteinosis secondary to sirolimus. Conclusions: All patients are alive. All 13 consecutive AugHaplo have > 90% chimerism. Viral reactivations are very frequent. Studies with larger cohorts and longer follow-up are needed to evaluate the long-term effects of this treatment strategy.