Haematopoietic stem cell transplantation for sickle cell disease – current practice and new approaches

Abstract

Sickle cell disease is an inherited disorder that affects over 5 million people worldwide. Current maintenance therapy has been successful in reducing complications and enhancing life expectancy; yet subclinical complications persist. To date, allogeneic haematopoietic stem cell transplant (HSCT) remains the only available curative therapy for sickle cell disease. With declining incidences of rejection and transplant- related mortality, disease-free survival after human leucocyte antigen-identical sibling transplant exceeds 90%. However, the majority of individuals with sickle cell disease do not have an human leucocyte antigen (HLA)-identical sibling; therefore, research is expanding to focus on new approaches to alternative donor transplant. Advances in supportive care and conditioning regimens have led to expansion of the pool of donors to unrelated donors and haploidentical donors. Challenges remain in improving the safety and efficacy of HSCT from alternate donors. Early results from gene therapy may provide another curative option in patients with sickle cell disease. These approaches show early promise, but larger, longitudinal studies are needed to better determine the optimal clinical circumstances for transplant in sickle cell disease.

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

“…11 Although several reports have demonstrated that HLA-identical sibling transplantation with bone marrow (BM) or umbilical cord blood (CB) establishes normal hematopoiesis and is associated with excellent survival, most studies were conducted at single institutions or in the context of clinical trials. [12][13][14][15][16][17] The current study sought to describe outcomes after HLA-identical sibling transplantation for SCD worldwide.…”

A trial of unrelated donor marrow transplantation for children with severe sickle cell disease

“…[2][3][4][5] HLAmatched sibling donor transplants account for the majority of transplants performed worldwide for hemoglobinopathy. 6,7 However, only 18% of patients with SCD have an HLA-matched sibling donor in the United States. 8 HLA-matched adult unrelated donors (URDs) have been used to expand the donor pool for nonmalignant hematologic disorders, but their role in SCD transplants is unclear.…”

Sickle cell disease: the price of cure

“…Crucially, ,1 in 10 of these families will have to cope with the major adverse outcome of BMT transplant-related mortality (TRM) and severe chronic graftversus-host disease (GVHD). 2,3 Given that SCD causes premature death and disability, particularly in young adults, and has a major impact on the quality of life for patients at all ages and their families, 4 these are convincing results. Can similarly impressive results be achieved for the 80% to 90% of patients with SCD who do not have HLA-matched family donors?…”

“…2,3 Overall, the outcome is extremely good, and BMT remains the best immediate prospect for long-term cure for children who are currently experiencing severe sickle-related complications. 2,3 Compared with other disease-modifying therapies, such as regular transfusion and hydroxycarbamide, matched related donor BMT will not only stop ongoing vaso-occlusive crises and arrest progressive organ damage in most cases, but may also lead to regression of damage in some cases. 3 Aggregate results from case series and clinical trials show disease-free survival of ;92% and overall survival (OS) of ;95% of children and young adults with SCD with a matched sibling donor.…”

“…2,3 Compared with other disease-modifying therapies, such as regular transfusion and hydroxycarbamide, matched related donor BMT will not only stop ongoing vaso-occlusive crises and arrest progressive organ damage in most cases, but may also lead to regression of damage in some cases. 3 Aggregate results from case series and clinical trials show disease-free survival of ;92% and overall survival (OS) of ;95% of children and young adults with SCD with a matched sibling donor. Crucially, ,1 in 10 of these families will have to cope with the major adverse outcome of BMT transplant-related mortality (TRM) and severe chronic graftversus-host disease (GVHD).…”