Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease

Abstract

Although there are a number of published trials of human leukocyte antigen (HLA) – identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and non-transplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with sickle cell disease treated and not treated by HCT. In this brief review, projections about mortality risk based upon recent published reports are reviewed and summarized. The published data show overall survival and event-survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival in the Center for International Blood and Marrow Transplant Research (CIBMTR) (N=412) and European Blood and Marrow Transplant (EBMT) (N=487) registries was 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with sickle cell disease and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears similar to results in children, and these preliminary observations warrant further investigation.

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

“…38 Consensus reports on indications for transplantation may increase awareness, with early referral for accepted indications. 17,39 Others have reported the observation that HLA-matched sibling transplantation performed in view of abnormal transcranial Doppler velocities allowed for discontinuation of transfusions in all patients. 12 Although survival in children has improved substantially over the years, the median survival of adults is about 20 years shorter than in the general population.…”

“…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.…”

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.…”

“…on June 7, 2019. by guest www.bloodjournal.org From haploidentical transplantation may offer a way forward. 2 The outcome of the SCURT study inevitably raises questions about the role of alternative donor stem cell transplantation in the management of children with SCD. Although the inclusion criteria for SCURT permitted unrelated donor BMT as an alternative to conventional disease-modifying treatment of recurrent vaso-occlusive crises or $2 episodes of acute chest syndrome in the preceding 2 years, for most such children, hydroxycarbamide is effective and well tolerated.…”