The role of cord blood transplantation in thalassemia

Abstract

More than 20 years ago, the first successful cure of β-thalassemia major by bone marrow transplantation was reported. Since then, more than 1500 patients have been treated in this manner. In Pesaro Italy where more than 1000 patients have received marrow transplantation, the 20-year probability of thalassemia-free survival is approximately 70%. Updated results strongly suggest that improved outcomes across risk categories have occurred as effective supportive care and conditioning regimen modifications have been applied to this setting. As with other non-malignant conditions, the alternative of increasingly effective supportive care also impacts upon the decision to pursue transplantation, even when transplant outcomes are very good. Umbilical cord blood (UCB) transplantation, thus, must compare favorably to proven therapeutic alternatives before its use can be expanded. UCB is an attractive alternative to other stem cell sources due to its decreased incidence of graft-versus-host disease (GVHD) and rapid tempo of immunological reconstitution after transplantation. Initial results of UCB transplantation for thalassemia suggest that acceptable outcomes are possible if measures are taken to mitigate the risk of graft rejection. Among 44 patients with sickle cell disease or thalassemia who received augmented conditioning therapy, the event-free survival was 94% compared to 62% among those who received a standard combination of busulfan and cyclophosphamide, with or without horse anti-thymocyte globulin. These early results also support the importance of banking efforts to expand the collection of related and unrelated UCB units. The clinical experience of unrelated UCB transplantation for thalassemia remains very limited. New techniques to prevent GVHD and promote engraftment, coupled with refined donor selection criteria should expand the availability of transplantation for thalassemia major. More than 20 years ago, the first successful cure of β-thalassemia major by bone marrow transplantation was reported. Since then, more than 1500 patients have been treated in this manner. In Pesaro Italy where more than 1000 patients have received marrow transplantation, the 20-year probability of thalassemia-free survival is approximately 70%. Updated results strongly suggest that improved outcomes across risk categories have occurred as effective supportive care and conditioning regimen modifications have been applied to this setting. As with other non-malignant conditions, the alternative of increasingly effective supportive care also impacts upon the decision to pursue transplantation, even when transplant outcomes are very good. Umbilical cord blood (UCB) transplantation, thus, must compare favorably to proven therapeutic alternatives before its use can be expanded. UCB is an attractive alternative to other stem cell sources due to its decreased incidence of graft-versus-host disease (GVHD) and rapid tempo of immunological reconstitution after transplantation. Initial results of UCB transplantation for thalassemia suggest that acceptable outcomes are possible if measures are taken to mitigate the risk of graft rejection. Among 44 patients with sickle cell disease or thalassemia who received augmented conditioning therapy, the event-free survival was 94% compared to 62% among those who received a standard combination of busulfan and cyclophosphamide, with or without horse anti-thymocyte globulin. These early results also support the importance of banking efforts to expand the collection of related and unrelated UCB units. The clinical experience of unrelated UCB transplantation for thalassemia remains very limited. New techniques to prevent GVHD and promote engraftment, coupled with refined donor selection criteria should expand the availability of transplantation for thalassemia major.