In a study with results reported in Lancet Haematology, researchers determined that for patients with severe hemoglobinopathies who were treated with allogeneic blood or marrow transplantation (BMT), improved outcomes were seen when total body irradiation (TBI) was given at 400 cGy instead of at 200 cGy.
In this phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT00489281), 12 patients with sickle cell disease, and 5 patients with b-thalassemia, were treated prior to BMT with nonmyeloablative conditioning that included antithymocyte globulin, fludarabine, cyclophosphamide, and TBI given at 400 cGy. Graft-versus-host disease (GVHD) prophylactic treatments were also given.
The primary study endpoint was assessment of engraftment in the intention-to-treat population. However, the study was terminated early based on funding circumstances, limiting the size of the study population. The planned analysis was not performed, but the researchers presented a description of results.
The median patient age was 16 years (range, 6-31). Donors had major ABO mismatches in 2 cases and minor ABO mismatches in 5 cases, but all donors were haploidentical relatives of patients. The median study follow-up was 705 days (range, 355-1294).
Out of the participants, 1 patient had graft failure, full donor chimerism was seen in 13 patients, and mixed donor-host chimerism was seen in 3 patients. Transfusion dependence remained in 1 of the 16 patients in which engraftment occurred, a patient with sickle cell disease. The 1 patient treated for sickle cell disease continued to have anemia and elevated hemoglobin S, but without sickle cell crises following BMT. Immunosuppression was discontinued in 14 patients.
Acute GVHD of grades 2 to 4 occurred in 5 patients. Chronic GVHD occurred in 3 patients, which reportedly had resolved. Sickle cell disease pain crises occurred in each patient with sickle cell disease upon receiving antithymocyte globulin.
Out of the participants, 1 patient with grade 3 GVHD also developed other adverse events, such as engraftment syndrome, idiopathic pneumonia syndrome, and grade 2 or 3 infections. An abnormal karyotype in host cells reportedly developed in 1 patient at 22 months following BMT, and this patient had also previously received hydroxyurea. There was 1 case each of grade 3 sirolimus-induced diabetes and grade 3 BK virus hemorrhagic cystitis.
“Our data demonstrate that increasing TBI from 200cGy to 400 cGy allows for stable engraftment and is well tolerated in hemoglobinopathy patients receiving haploBMT,” the study investigators concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Bolaños-Meade J, Cooke KR, Gamper CJ, et al. Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial. Lancet Haematol. 2019;6(4):e183-e193. doi:10.1016/S2352-3026(19)30031-6