Allogeneic hematopoietic stem cell transplantation from sibling and unrelated donors in pediatric patients with sickle cell disease—A single center experience

Abstract

HSCT is curative in SCD. Patients with HLA‐identical sibling donor have an excellent outcome ranging from 90%‐100% overall and event‐free survival. However, due to the lack of matched sibling donors this option is out of reach for 70% of patients with SCD. The pool of potential donors needs to be extended. Transplantations from HLA‐matched unrelated donors were reported to be less successful with shorter event‐free survival and higher incidences of complications including graft‐vs‐host disease, especially in patients with advanced stage SCD. Here we report transplantation outcomes for 25 children with SCD transplanted using HLA‐matched grafts from related or unrelated donors. Overall survival was 100% with no severe (grade III‐IV) graft‐vs‐host disease and a 12% rejection rate. Mixed donor chimerisms only occurred in transplantations from siblings, while transplantations from unrelated donors resulted in either complete donor chimerism or rejection. Despite the small patient number, overall and disease‐free survival for unrelated donor transplantations is excellent in this cohort. The advanced disease state, higher alloreactive effect and stronger immunosuppression in unrelated donor transplantations raises patient risk, for which possible solutions could be found in optimization of transplant preparation, graft manipulation or haploidentical transplantation using T cell receptor α/β‐depleted grafts.

The effect of intensity of conditioning regimen on the outcome of HSCT in children with sickle cell disease

“…The findings for unrelated donor transplantation in previous studies were inconsistent with some reporting high rates of GVHD and viral infections, poor OS, and high rejection rates 16,26,27 . Studies reporting higher rates of successful outcomes like overall survival and lower rejection and complication rates as in the present study were often limited by the small number of children with SCD who underwent transplantation with unrelated donor grafts 28–30 …”

“…16,26,27 Studies reporting higher rates of successful outcomes like overall survival and lower rejection and complication rates as in the present study were often limited by the small number of children with SCD who underwent transplantation with unrelated donor grafts. [28][29][30] The definition of secondary graft failure in SCD is not clear. Previous studies have used different cut-off points to define it; for example, less than 20% donor chimerism.…”

Across the Myeloablative Spectrum: Hematopoietic Cell Transplant Conditioning Regimens for Pediatric Patients with Sickle Cell Disease

“…Outcomes for pediatric regimens employing a Bu/Cy conditioning have been excellent: overall survival (OS) rates range from 90 to 100% and event-free survival (EFS) from 77 to 100% [13,[16][17][18][19][20][21][22][23][24][25]. On the other hand, the same reports describe grade II-IV aGVHD in 11-39% of patients.…”

“…On the other hand, the same reports describe grade II-IV aGVHD in 11-39% of patients. The BU/Cy regimen is associated with cGVHD rates ranging from 0 to 21%, though GVHD prevention strategies vary [13,[16][17][18][19][20][21][22][23][24][25].…”

Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients

“…To date, hundreds of SCD patients have already been successfully transplanted worldwide ( 29 , 31 ). Patients with HLA-identical sibling donors have high overall and event-free survival rates, ranging from 90% to 100% ( 29 , 32 ). The graft rejection rate (graft failure) varies extensively among different studies ( 31 ) and addition of anti-thymocyte globulin (ATG) to the transplant regimen is associated with a decrease in the incidence of graft rejection from 22.6% to 3% ( 33 ).…”