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Patients with Thalassaemia Major Who Are Transplanted with Peripheral Blood and Marrow Survive Longer than Those Transplanted with Cord Blood and Marrow
March 10, 2017-Hong Kong, China — In thalassaemia major, grafts composed ofperipheral blood + bone marrow led to superior overall outcomes than those composed ofcord blood + bone marrow, as evidenced by faster engraftment and lower transplant-related mortality of the former despite substantially lower rates of acute and chronic graftvs host disease of the latter.
This outcome of a prospective, open-label, single-centre clinical trial was reported at the58th Annual Meeting of the American Society of Hematology, from December 3 – 6.
Qiao Chuan Li, MD, of Guangxi Medical University/the First Affiliated Hospital,Nanning, China, explained that thalassaemia major is a fatal genetic disease curable onlywith allogeneic stem cell transplantation. Allogeneic stem cell transplantation is limited,however, by the lack of suitable donors and quantity of collected stem cells. Theprocedure is often complicated by graft rejection and graft vs host disease.
Dr Chuan Li and colleagues compared the outcomes of patients with thalassaemia majorwho were transplanted with matched sibling cord blood and bone marrow grafts vsmatched sibling peripheral blood stem cell and bone marrow grafts.
A total of 204 patients with thalassaemia major were enrolled between 2007 and 2015and transplanted with either peripheral blood + bone marrow (n=99) or cord blood +bonemarrow (n=105), from an HLA-identical sibling donor.
The primary endpoint was 2-year thalassaemia-free survival. Secondary endpointsincluded 2-year overall survival, the cumulative incidence of graft vs host disease,transplant-related mortality, and graft rejection. The conditioning regimens were:
- Busulphan 1.25 mg per kilogram of body weight given orally four times per day for 4days or 1 mg per kilogram of body weight given intravenously four times per day for 4days (day -9 to day -6)
- Fludarabine 50 mg/m2 daily given intravenously for 3 days (day -12 to day -11)
- Cyclophosphamide 50 mg per kilogram of body weight given intravenously for 4 days(day -5 to day -4)
- Antithymocyte globulin 2.5 mg per kilogram of body weight daily given intravenouslyfor 4 days (days -4 and day -1)
All patients were placed on 30 mg per kilogram of body weight of hydroxyurea orallyonce daily for 2 - 3 months before transplantation. Prophylaxis against graft vs hostdisease consisted of a combination of cyclosporine A, methotrexate, and mycophenolatemofetil.
Data cutoff for survival follow-up was March 31, 2016. The median follow-up time was26 (range 4 – 105) months. Both neutrophil as well as platelet engraftment occurred significantly faster in the peripheral blood + bone marrow group than the cord blood +bone marrow group (11 vs 13 days, P = .001 and 15 vs 25 days, P = .001, respectively).The rate of graft failure was the same in both groups (1.0%).
The cumulative incidence of grade II - IV acute and extensive chronic graft vs hostdisease in the peripheral blood + bone marrow group was higher than in the cord blood +bone marrow group: acute graft vs host disease 15.5% vs 1.0%, P = .001; chronic graft vshost disease 6.4% vs. 0%, P = .013.
The cumulative rates of transplant-related mortality at 2 years remained significantlylower in the peripheral blood + bone marrow group than in the cord blood + bone marrowgroup with 2.0% and 12.5%, P = .005, respectively.
Both overall and thalassaemia-free survival at 2 years favored the peripheral blood +bone marrow group over the cord blood + bone marrow group: overall survival 98% vs86.5%, P= .003; thalassaemia-free survival 97% vs 86.5%, P = .008.
Dr Chuan Li concluded that in thalassaemia major, grafts composed of peripheral blood +bone marrow led to superior overall outcomes vs cord blood + bone marrow grafts, asevidenced by faster engraftment and lower transplant-related mortality of the formerdespite substantially lower acute and chronic graft vs host disease rates of the latter.
The mixed stem cell populations and high cell dose achieved with two different graftsources, together with the conditioning regimen used, likely contributed to the superioroutcomes seen with this regimen. The strategy could be of great benefit for patients withthalassaemia major and other benign haematologic disease.