ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia.

Matched-related bone marrow transplantation (BMT) may cure >80% of low-risk children with severe thalassemia (ST). Very long-term follow-up studies have shown how the standard busulfan-cyclophosphamide (BuCy) regimen may be associated with normalization of health-related quality of life, no second malignancies in the absence of chronic graft-versus-host disease, and fertility preservation in many patients. However, because BuCy may be associated with high rejection rates, some centers incorporate thiotepa (Tt) in busulfan- or treosulfan-based regimens, a combination that may increase the risk of permanent infertility. This study retrospectively compares matched-related BMT outcomes in 2 groups of low-risk ST patients conditioned with either Tt or anti-thymocyte globulin (ATG) in addition to BuCy. A total of 81 consecutive first BMTs were performed in 5 collaborating startup BMT centers in the Indian subcontinent between January 2009 and January 2016; 30 patients were transplanted after conditioning with Tt-BuCy between January 2009 and July 2013, whereas between August 2013 and January 2016, 51 patients received ATG-BuCy. All patients were <15 years and had no hepatomegaly (liver ≤2 cm from costal margin). Actuarial overall survival in the Tt-BuCy and ATG-BuCy groups was 87% and 94% and thalassemia-free survival was 80% and 85% at a median follow-up of 37 and 17 months, respectively, with no significant differences by log-rank statistics. Substituting Tt with ATG in the standard BuCy context seems safe and effective and may decrease transplant-related mortality. Higher fertility rates are expected for patients who received ATG-BuCy.