ORLANDO – For patients with severe sickle cell disease, stem cell transplants from an HLA identical sibling are associated with “excellent” 3-year overall and event-free survival, results of a retrospective analysis show.
Data on 1,000 hematopoietic stem cell transplants (HSCT) in children and adults with sickle-cell disease performed in 88 centers in 23 countries showed a 3-year event-free-survival (EFS) rate of 90%, and 3-year overall survival (OS) rate of 94%, reported Dr. Barbara Cappelli from the Eurocord International Registry in Paris, France.
“Early referral to transplant for patients with severe sickle-cell disease is warranted, as age is an independent predictor for both event-free survival and overall survival,” she said about the study at a briefing at the American Society of Hematology annual meeting.
Patients who received donor cord blood had the best 3-year OS, at 99%, compared with 94% for patients who received bone marrow grafts, and 80% for those who received peripheral blood stem cells (PBSC).
“Transplants from peripheral blood are not recommended, because the result that there is higher mortality with transplants with peripheral blood,” she said.
The findings provide further evidence that for patients with severe sickle-disease who have an HLA-identical sibling available as a donor, HSCT can be curative with good safety, commented Dr. Alexis Thompson, a professor of hematology at the Robert H. Lurie Children’s Hospital of Chicago, Illinois.
Dr. Thompson was not involved in the study, but moderated a briefing where the data were presented.
HSCT is the only therapy currently known to be curative for sickle-cell disease, but due to the risk for early and late complications it is generally reserved for patients with the most severe anemia or most disabling symptoms.
To evaluate the efficacy and safety of HSCT for sickle-cell disease, the investigators took a retrospective look at data from bone marrow transplant registries covering Europe, Brazil, the United States, and other reporting centers.
They searched for data on all patients with sickle-cell disease, children and adults, who received a transplant from an HLA identical sibling from 1986 through 2013.
The majority of patients (85%) were younger than 16, with the median age at HSCT of 9 years (range 1 to 54 years). Stroke was the most common indication for HSCT.
In all, 87% of patients received a myeloablative conditioning regimen based on busulfan combined with either cyclophosphamide or fludarabine. The remaining 13% of patients underwent a reduced-intensity conditioning regimen, primarily with fludarabine and cyclophosphamide.
In vivo T-cell depletion was performed in 70% of patients, either with anti-thymocyte globulin (630 patients) or with alemtumumab (76).
Prophylaxis for graft vs. host disease (GVHD) was predominantly cyclosporine as monotherapy or in combination with methotrexate.
A large majority of patients (84%) received bone marrow grafts, 7% got PBSCs, and 9% received umbilical cord blood.
By 60 days, the cumulative incidence of engraftment was 98%, with a median cumulative incidence of platelet engraftment of 25 days.
The cumulative incidence of acute GVHD (within 100 days of transplant) 14.3%, and the cumulative incidence of chronic GVHD (out to 3 years) was 13.3%
In all, 71 patients (7%) required autologous reconstitution, 45 because of late graft failure, 31 patients (3%) underwent a second transplant and 67 patients (7%) died. Of the patients who died, 6% had received bone marrow, 1% had received cord blood, and 21% had received PBSC.
As noted before, respective EFS and OS 3 years after transplant were 90% and 94%.
In multivariate analysis controlled for transplant and demographic characteristics, the authors found that younger age at transplant and use of bone marrow or cord blood were independently associated with better EFS and OS. In addition, 3-year overall survival was significantly better among patients who received transplants from the year 2000 on.
The risk for acute GVHD was significantly associated with increasing age, but none of the variables tested were associated with chronic GVHD.
Dr. Cappelli said that ways to improve outcomes include performing pre-or post-natal diagnosis in at-risk families, performing HLA typing of all family members at the time of diagnosis, and going to transplant as soon as the criteria for severe sickle-cell disease are met.
The study was supported by Eurocord-Monacord, EBMT Paediatric Disease Working Party and CIBMTR. Dr. Cappelli and Dr. Johnson reported having no conflicts of interest.