Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease: Myeloablative Versus Reduced Intensity Conditioning

Abstract

<h3>Background</h3> Sickle cell disease (SCD) is prevalent in Saudi Arabia. We reviewed transplant outcome among SCD patients who underwent HLA-matched related donor HSCT at our institution using either myeloablative or reduced intensity conditioning (RIC) <h3>Methods</h3> myeloablative conditioning (MAC) regimen was intravenous (IV) busulfan (Bu) 16mg/kg, cyclophosphamide (Cy) 200mg/kg, and rabbit anti-thymocyte globulin (ATG) 10mg/kg (BuCyATG) and recently we use TBF regimen (thiotepa 8mg/kg, IV Bu 16mg/kg, and fludarabine 160mg/m²). GVHD prophylaxis included calcineurin inhibitor (CNI) and methotrexate (10mg/m²) on day 1, 3, and 6. CNI was continued for one year post transplant then tapered slowly. Based on parental preference, we used RIC regimen that included alemtuzumab, fludarabine, and melphalan (AFM) in 4 patients as reported by (King et al. AJH 2015). Three patients participated in a pilot RIC study (NCT02776202) which included pre-conditioning hydroxyurea (40mg/kg) from day -60 to day -10 and intensive iron chelation if needed followed by conditioning that included ATG 10 mg/kg, fludarabine 175mg/m², and melphalan 140 mg/m² (ATGFM) with GVHD prophylaxis consisting of mycophenolate mofetil from day -3 to +45 and sirolimus from day -1 until at least one year post transplant. Bone marrow was the source of stem cells in all patients. SCD-specific supportive care was implemented <h3>Results</h3> A total of 41 SCD patients were transplanted, 34 received MAC and 7 RIC. Indications for HSCT were recurrent pain crisis (n=25), stroke or abnormal transcranial doppler (n=13), and other (n=3). Patient and transplant characteristics are shown in Table. All patients who underwent MAC are alive and free of SCD at a median follow up of 444 days. Among patients who received RIC, 4 had late graft failure with autologous recovery. Of those, two underwent successful second HSCT using MAC and 2 patients are alive with SCD. In addition, 2 patients who received RIC (1 AFM and 1 ATGFM) are off immunosuppressant with full donor chimerism more than 2 years post-transplant and one patient (ATGFM) is still on sirolimus at 351 days post-transplant with low donor chimerism. There was no mortality in our study <h3>Conclusions</h3> MAC HSCT in SCD is well tolerated and associated with excellent outcome. There is high rate of late graft failure with the use of RIC in SCD.