Matching sibling peripheral blood–based grafts improve outcomes for thalassemia major

SAN DIEGO — The use of matched sibling peripheral blood stem cell and bone marrow grafts led to faster engraftment and a reduction in transplant-related mortality compared with matched sibling cord blood and bone marrow grafts in patients with thalassemia major, according to results of a prospective, single-center trial presented at the ASH Annual Meeting and Exposition.

“Over 300,000 children are born each year with hemoglobinopathy, of whom more than 25,000 have thalassemia major, and there are about 300,000 patients with thalassemia major and intermedia in China,” Qiao chuan Li, MD, hematologist at Guangxi Medical University/The First Affiliated Hospital in Nanning, China, said during his presentation. “Hematopoietic stem cell transplantation is the only curative therapy but is limited by a lack of suitable donors, quantity of collected stem cells, graft-versus-hosts disease [GVHD] and graft rejection.”

The graft source — bone marrow, peripheral blood or cord blood — significantly impacts the rate of engraftment, disease recurrence and the incidence of GVHD.

Li and colleagues compared the outcomes of 204 patients (median age, 4 years; range, 2-16; 69.6% boys) with thalassemia major transplanted with matched sibling cord blood and bone marrow grafts (n = 105) with those transplanted with matched sibling peripheral blood stem cell and bone marrow grafts (n = 99).

Two-year thalassemia-free survival served as the study’s primary endpoint. Secondary endpoints included 2-year OS, incidence of GVHD, transplant-related mortality and graft rejection.

Patients received an induction regimen of bulsulphan (1.25 mg/kg orally four times a day for 4 days or 1 mg/kg IV four times per day for 4 days), fludarabine (50 mg/m² IV dose daily for 3 days), cyclophosphamide (50 mg/kg daily IV dose for 4 days) and antithymocyte globulin (Genzyme; 2.5 mg/kg daily IV dose for 4 days). Further, patients received 30 mg/kg hydroxyurea once daily for 2 to 3 months prior to transplantation.

GVHD prophylaxis included cyclosporine A, methotrexate and mycophenolate mofetil.

Median follow-up was 26 months (range, 4-105).

Patients in the peripheral blood graft group experienced significantly faster time to neutrophil (11 days vs. 13 days; P = .001) and platelet (15 days vs. 25 days; P = .001) engraftment.

Graft failure occurred in 1% of patients in each arm.

More patients in the peripheral blood group experienced acute GVHD (15.3% vs. 1%; P = .001) and chronic GVHD (6.2% vs. 0%; P = .013). However, 2-year transplant-related mortality was lower in the peripheral blood arm (2% vs. 13.3%; P = .005). Two-year OS (98% vs. 85.7%; P = .003) and thalassemia-free survival (97% vs. 85.7%; P = .008) also favored the peripheral blood arm.

“The excellent survival outcomes in our study may be related to the use of antithymocyte globulin, a higher cell dose infusion and the intensive conditioning regimen,” Li said. “This strategy could be of great benefit for the treatment of patients with thalassemia major and other hematologic diseases.” – by Alexandra Todak

Reference:

Li QC, et al. Abstract 847. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: The researchers report no relevant financial disclosures.