HLA–identical sibling transplantation showed promising long-term survival for children and adults with sickle cell disease, according to an international retrospective study.
“Sickle cell disease and transplant physicians alike debate the burden of morbidity from a chronic disease and mortality from the disease, vs. the curative option with transplantation and the risk for transplant-related complications and mortality,” Eliane Gluckman, MD, from the Eurocord Hospital Saint Louis in Paris, France, and colleagues wrote.
Experts recommended young patients with symptomatic sickle cell disease and an HLA–identical sibling to undergo transplantation as early as possible, and for alternative transplantation to only be considered with the presence of disease severity markers.
Reports have demonstrated that HLA–identical sibling transplantation with bone marrow or umbilical cord blood results in hematopoiesis and improved survival. However, much of this data was derived from single institutions or clinical trials. Thus, Gluckman and colleagues sought to describe outcomes after HLA–identical sibling transplants for sickle cell disease worldwide.
The researchers evaluated the outcomes of 1,000 recipients of HLA–identical sibling transplants that were performed between 1986 and 2013 and reported to the European Blood and Marrow Transplant, Eurocord and the Center for International Blood and Marrow Transplant Research.
EFS served as the primary endpoint.
Median age at transplantation was 9 years (range, 0.3-16) among children (n = 846) and 20 years (range, 16-54) among adults (n = 154).
Median follow-up for surviving patients was 55 months (range, 3-325).
Patients received a myeloablative conditioning regimen (87%) or reduced-intensity conditioning regimens (13%). Stem cell sources included bone marrow (n = 839), peripheral blood (n = 73) and umbilical cord blood (n = 88).
Neutrophil recovery at more than 60 days occurred in 98% of patients (95% CI, 97.1-98.9), and granulocyte recovery occurred after a median of 19 days.
Platelet engraftment at 6 months occurred in 96% of patients, after a median 25 days.
Twenty-three patients experienced graft rejection.
Chronic graft-versus-host disease (GVHD) occurred in 14.3% of patients (95% CI, 12-16.9). Multivariate analysis demonstrated the risk for acute GVHD was higher with increasing age (HR for each year older = 1.04; 95% CI, 1.01-1.07).
“Our data support early referral for transplantation when an indication is identified, so that donor search and transplantation of bone marrow, peripheral blood or banked cord blood from an HLA–identical sibling can be initiated in a timely manner,” Gluckman and colleagues wrote.
Rate of 5-year OS was 92.9% (95% CI, 91.1-94.6) and 5-year EFS was 91.4% (95% CI, 89.6-93.3).
Multivariate analysis showed EFS was lower with increasing age at transplantation (HR for each year older = 1.09; 95% CI, 1.05-1.12) and higher for transplantations performed after 2006 (HR = 0.95; 95% CI, 0.9-0.99).
Overall, 70 patients died; the most common cause of death was infection (n = 14), followed by GVHD (n = 9), toxicity (n = 9), hemorrhage (n = 3), secondary malignancy (n = 2), and other or not specified causes (n=33).
“Transplantation of grafts from HLA–identical siblings offers excellent 5-year survival and our results confirm this is an accepted treatment for severe sickle cell disease worldwide,” the researchers wrote. “Nevertheless, it is also important to study the effects of transplantation on the long term and to develop prospective trials of comparable patient cohorts to determine the relative merits of transplantation vs. supportive care, especially in older patients with severe sickle cell disease.” – by Kristie L. Kahl
Disclosure: The researchers report no relevant financial disclosures.