The U.K. NHS has begun offering hematopoietic stem cell transplantation (HSCT) to adults suffering from transfusion-dependent thalassemia, with projections indicating that up to 70% of these patients may survive for 23 years post-transplant.

While gene therapy is emerging as a promising alternative for treating beta-thalassemia, HSCT remains the only widely accessible curative option at present.

Two gene therapies, Zynteglo and Casgevy, have been approved for beta-thalassemia treatment; however, they still necessitate toxic conditioning regimens and come with high costs.

Dr. Robert Brodsky highlights that advancements in HLA typing and engraftment techniques have led to improved outcomes in HSCT, particularly with the use of post-transplant cyclophosphamide to reduce graft-versus-host disease (GVHD).

Recent improvements in conditioning regimens and T-cell depletion have enhanced HSCT success rates, especially when using alternative donors, thereby reducing reliance on perfectly matched siblings.

Transplant outcomes are notably better when the procedure is performed before the age of 14, with overall survival rates reaching as high as 96%.

A 2016 study revealed that the overall survival (OS) and event-free survival (EFS) rates for HSCT in patients under 18 were 88% and 81%, respectively, with the best results observed in those receiving transplants from HLA-matched sibling donors.

A Chinese study reported impressive 2-year OS and EFS rates of 95% for transfusion-dependent thalassemia patients, noting lower transplant-related mortality in matched sibling cohorts.

Dr. Faulkner emphasizes the importance of early transplantation, stating that younger patients are preferred due to the risks of irreversible organ damage from chronic transfusions, which can manifest by age 8.

Children under 8 years old are considered ideal candidates for HSCT, with favorable outcomes extending up to age 15 if adequate pre-transplant care is administered.

A 2020 study indicated that haploidentical donor HSCT for severe thalassemia patients achieved projected 3-year OS and EFS rates of 96%, demonstrating results comparable to those from matched donor transplants.

Dr. Brodsky argues that while gene therapy represents an exciting advancement, it must continue to evolve to become a more viable option for patients lacking suitable donors.