What are the indications for Stem Cell Transplantation (SCT) in Beta-Thalassemia Major?

From the Guidelines

Stem cell transplantation (SCT) is indicated for patients with thalassemia major who have a matched sibling donor, ideally before complications of iron overload develop, as it offers the only curative option for the disease. The primary indications for SCT in thalassemia major include:

• Transfusion dependence requiring regular blood transfusions every 3-4 weeks
• Evidence of iron overload despite chelation therapy
• Risk of developing serious complications like cardiac disease, liver fibrosis, or endocrine abnormalities SCT is most successful when performed early in life, typically before age 14, and before significant organ damage occurs, as reported by 1. The Pesaro risk classification helps determine transplant outcomes, with Class 1 patients (no hepatomegaly, no portal fibrosis, adequate iron chelation) having the best prognosis. Patients with HLA-matched siblings have better outcomes, though matched unrelated donor transplants are increasingly successful, as shown in studies such as 1. The procedure involves myeloablative conditioning with busulfan and cyclophosphamide, followed by infusion of donor stem cells. SCT offers the only curative option for thalassemia major, eliminating the need for lifelong transfusions and chelation therapy, though it carries risks of graft rejection, graft-versus-host disease, and transplant-related mortality ranging from 5-20% depending on risk factors.

Key considerations for SCT in thalassemia major include:

• Age: SCT is most successful when performed early in life, typically before age 14
• Donor availability: Patients with HLA-matched siblings have better outcomes, though matched unrelated donor transplants are increasingly successful
• Organ damage: SCT is most successful when performed before significant organ damage occurs
• Iron overload: Control of iron overload and related tissue damage is a key issue for transplant outcome, as reported by 1.

Overall, SCT is a highly effective treatment option for patients with thalassemia major, offering the potential for a cure and elimination of the need for lifelong transfusions and chelation therapy, as supported by studies such as 1 and 1.

From the Research

Indications of SCT in Thalassemia Major

• Thalassemia major is an autosomal recessive disorder associated with defective synthesis of the α- or β-chain of hemoglobin 2.
• SCT is the only curative approach for thalassemia major, with success inversely correlated with the degree of iron overload and hepatic damage 2.
• Patients undergoing transfusion therapy remain at risk for transmitted infections and iron overload with associated tissue damage, making SCT a preferred option 2.
• The use of unrelated donors and novel approaches such as gene therapy are under current investigation 2, 3.

Patient Selection for SCT

• Patients with an HLA-identical donor should be offered SCT, as the probabilities for obtaining thalassemia-free survival after transplant are between 85 and 87% 3.
• High-risk patients, such as those with iron overload and hepatic damage, may benefit from hypertransfusion therapy and aggressive chelation in addition to hydroxyurea, azathioprine, and fludarabine to decrease graft rejection 2.
• Patients with advanced thalassemia major, including those with liver fibrosis and inadequate iron chelation, require further development of new treatment regimens to improve clinical outcomes 4.

Conditioning Regimens for SCT

• Busulfan and cyclophosphamide-based conditioning regimens are effective and safe for allogeneic transplantation in patients with transfusion-dependent thalassemia, even in high-risk patients 5.
• Treosulfan-based conditioning regimens have emerged as an alternative due to concerns of toxicities, but may have a higher risk of graft-versus-host disease and treatment-related mortality 5.
• The choice of conditioning regimen should be individualized based on the patient's risk factors and disease status 4.