# Curative Approach to the Treatment of Beta-Thalassemia and Sickle Cell Disease with Hematopoietic Stem Cell Transplantation

## TL;DR

This paper discusses how hematopoietic stem cell transplantation and gene therapy can cure beta-thalassemia and sickle cell disease, emphasizing the importance of early treatment and donor availability.

## Contribution

The paper highlights the increasing viability of haploidentical stem cell transplantation and the limitations of gene therapy in accessibility and cost.

## Key findings

- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is most effective when performed early in life to prevent disease complications.
- Haploidentical HSCT is becoming a viable option for more patients due to its increasing use in treating beta-thalassemia and sickle cell disease.
- Gene therapy remains limited in availability due to high costs and infrastructure requirements.

## Abstract

β-thalassemia and sickle cell disease are two inherited hematological diseases due to defective hemoglobin synthesis or to the production of hemoglobin with altered properties. These two conditions have prolonged survival with modern support therapies, albeit life-long, complex, expensive and resource-consuming. Studies carried out in the last three decades have shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) and gene therapy may offer a curative approach for these diseases. Allo-HSCT should be performed early in life to reduce disease-related complications like irreversible tissue damage due to iron overload in patients with transfusion-dependent β-thalassemia (TDT) and systemic vasculopathy in patients with sickle cell disease (SCD). HSCTs from a matched-sibling donor or a matched-unrelated donor represent the best therapeutic option; however, haploidentical HSCT in both TDT and SCD is now increasingly performed as a valuable and viable option for a larger number of these patients. An alternative curative strategy is based on gene therapy. These curative approaches, particularly those of gene therapy, are available only in a part of the world. Gene therapy diffusion is strongly limited by its high technological and infrastructure requirements and its very high cost. Criteria must be defined for the optimal selection of TDT and SCD patients for allo-HSCT or gene therapy.