Amir Ali Hamidieh, Maryam Behfar
Thalassaemia major (TM) is one of the most common hereditary haematologic disorder with insufficient production of red blood cells. Although regular blood transfusion relieves the complication such as anaemia, bone marrow expansion, heart failure and growth retardation, it causes more severe side effects due to iron overload and eliminate the overall survival. The first haematopoietic stem cell transplantation (HSCT) in TM patients was carried out more than three decades ago. Today although gene therapy is the potential novel therapeutic option for thalassaemia, HSCT is the sole available curative treatment worldwide for these patients.
HSCT outcome is influenced by patient’s age, type of donor, stem cell source and Pesaro risk classification before transplant. Older patients, especially who with iron over load and/or evidence of alloimmunization duo to multiple transfusion have a higher risk of toxicities, graft rejection, graft-versus-host disease (GvHD), and transplant-related mortality. According to EBMT report, patients under 14 years old are the best transplant candidates to achieved optimal outcome in matched family donor HSCT.
The best clinical outcomes of HSCT in thalassaemia major are reported in those with human leukocyte antigen (HLA) identical sibling donors. However, lack of HLA-identical sibling is one of the major limitations in HSCT. Matched other related/unrelated donor are widely used in these patients. Using high-resolution molecular typing for both HLA class I and II loci and optimization of conditioning regimens, GvHD prophylaxis and supportive care have significantly improved transplant outcomes in other related/unrelated setting compared with matched sibling donors. All related donor candidates must be assayed for this genetic disorder before donation.
Although recently the use of non-myeloablative conditioning reported in some studies, myeloablative conditioning regimen with or without anti-thymocyte globulin has been accepted as a standard conditioning regimen for TM.
After a successful transplant, patients become transfusion independent but the untreated already iron overload impacts on patient’s quality of life and their lifespan. Therefore, close observation of iron accumulation by non-invasive method such as T2 MRI and/or elastography are recommended and management of iron overload with phlebotomy or chelation therapy should be considered.
Correspondence: Professor Amir Ali Hamidieh, Professor at Children’s Medical Centre, Tehran, Director of Paediatric Cell Therapy Research Centre, Tehran University of Medical Sciences, Tehran, Iran. Email: [email protected]