Allogeneic hematopoietic stem cel transplant for sickle cell disease: The time is now

Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Blood (Impact Factor: 10.45). 05/2011; 118(5):1197-207. DOI: 10.1182/blood-2011-01-332510
Source: PubMed


Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. However, adult patients have been excluded from myeloablative allo-HSCT because of anticipated excess toxicity resulting from accumulated disease burden. Efforts to use nonmyeloablative transplantation strategies in adults logically followed but were initially met with largely disappointing results. Recent results, however, indicate that nonmyeloablative allo-HSCT in adult patients with SCD allows for stable mixed hematopoietic chimerism with associated full-donor erythroid engraftment and normalization of blood counts, and persistence in some without continued immunosuppression suggests immunologic tolerance. The attainment of tolerance should allow extension of these potentially curative approaches to alternative donor sources. Efforts to build on these experiences should increase the use of allo-HSCT in patients with SCD while minimizing morbidity and mortality.

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    • "Recently, transplantation trials in humans and numerous animal studies have shown that complete correction or replacement of the hematopoietic stem cell pool or correction of the βS point mutation itself are not required to provide therapeutic benefits [18-20]. Given these encouraging trials and the natural history of sickle cell trait, we sought to introduce a competing anti-sickling globin gene to HSCs to test for potential phenotypic correction. "
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    • "For the best chance at transplant success, a HLA-matched family donor is needed, but is only available in 14–18% of children with SCA. The major risks of transplant include infection, graft-versus-host disease (GVHD), failure to engraft, and death(Hsieh, et al 2011). Early concerns about central nervous system (CNS) complications, such as seizures, associated with transplantation appear to have been ameliorated by aggressive treatment with platelets and anti-convulsant medication. "
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