Allogeneic Stem Cell Transplantation for Thalassemia Major

Abstract

At present an allogeneic stem cell transplant remains the only curative option for patients with β-thalassemia major. Even with the potential advent of gene therapy in the near future, it is likely to remain the least expensive curative therapy in the foreseeable near future. Currently in patients with good risk features, it is reasonable to anticipate a greater than 90% chance of a successful transplant outcome. Parameters for risk stratification prior to an allogeneic stem cell transplant for this disorder are unique and distinct. The conventional risk stratification system has limitations, and alternative systems are being explored to better identify subsets that require innovative approaches to improve their outcome. A number of novel regimens have been evaluated in an effort to reduce treatment-related morbidity and mortality. Regimen-related toxicity profile posttransplantation in these patients is characterized by an increased incidence of sinusoidal obstruction syndrome, more so in the high-risk cases. There remain challenges in improving the clinical outcome of high-risk patients, especially in developing countries, where inadequate blood transfusion and chelation prior to transplant and an older age at which patients opt for transplant lead to an increased risk of graft rejection and treatment-related mortality. With the increase in the donor pool by the use of matched unrelated donors, cord blood stem cells, and haploidentical donors, more patients can potentially access this curative therapy. However, these alternate donor sources come with their own challenges, and significant improvements need to occur before they can be considered standard of care. Better understanding of graft characteristics and immune reconstitution posttransplant has the potential to identify interventions to further improve the short- and long-term clinical outcomes.