Transplantation for thalassemia major: alternative donors

Lack of a human leukocyte antigen (HLA)-matched family donor is a major obstacle limiting the use of allogeneic hematopoietic stem cell transplantation (HSCT) to cure thalassemia major. Use of alternative donors, if found well tolerated enough, may be a viable option for transplantation in this setting, allowing to expand the number of patients treatable by HSCT. This review will provide an overview of alternative HSCT approaches in thalassemia major.

With the introduction of high-resolution molecular HLA-typing techniques, the outcome of matched unrelated donor HSCT recipients has become comparable with that of patients given matched family donor HSCT. On the contrary, the use of unrelated cord blood transplantation has been limited by the risk of graft failure and slow hematopoietic recovery, although novel techniques of ex vivo graft manipulation are emerging as promising strategies for overcoming these obstacles. Although experience with haploidentical HSCT in thalassemia major is still limited, currently explored platforms hold the potential to extend the access to HSCT to thalassemia major patients lacking an HLA-matched either related or unrelated donor.

The significant advances achieved in transplantation techniques, both in the matched unrelated and in the haploidentical setting, are expected to significantly broaden the applicability of HSCT to patients with thalassemia major.