The only curative treatment available for thalassemia currently is HSCT. There is now extensive experience with transplantation, with several thousand patients having undergone the treatment.  Historically, risk classification was based on three criteria: hepatomegaly, the degree of portal fibrosis, and the degree of iron overload. In class 1 without adverse factors, the overall survival rate is 95%, and the event-free survival rate (without thalassemia) is 90%; class 2 patients with one or two risk fac tors have an 85% survival and an 81% event-free survival; and class 3 patients with all three risk factors have only 64% and 62% overall and event-free survival rates, respectively (Fig.1). Advances in conditioning regimens have considerably improved the outcome of class 3 patients who are younger than 17 years of age. Preparatory chemotherapeutic regimens to enhance immunosuppression and eradicate thalassemic clones using hydroxyurea, azathioprine, fludarabine, busulfan, and cyclophosphamide have increased the survival rate of class 3 patients to 93%; the rejection rate fell to 8%. These favorable results have not been reproduced in the older, more heavily iron-overloaded patients who remain high risk for transplant-related mortality.

Fig1. FAVORABLE OUTCOMES FOLLOWING ALLO-HSCT ARE ACHIEVED IN YOUNGER PATIENTS WITH HLA-MATCHED RELATED DONOR. The greatest 5-year probability of overall survival was observed in patients ≤ 6 years of age or who had an HLA-matched related donor.1 Only a minority of patients with TDT undergo allo-HSCT with the majority of those being less than 14 years old with an HLA-matched sibling donor, well controlled iron, and lacking iron-related morbidities. 2–6 Allo-HSCT, Allogeneic hematopoietic stem cell transplantation; HLA, human leukocyte antigen; TDT, transfusion-dependent β -thalassemia.

References: ¹Li C, Mathews V, Kim S, et al. Related and unrelated donor transplantation for β -thalassemia major: results of an international survey. Blood Adv. 2019;3(17):2562–2570. ²Baronciani D, Angelucci E, Potschger U, et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplant. 2016:51(4):536–541. ³Marziali M, Isgrò A, Gaziev J, Lucarelli G. Hematopoietic stem cell transplantation in thalassemia and sickle cell disease. Unicenter experience in a multi-ethnic population. Mediterr J Hematol Infect Dis. 2009;1(1):e2009027. ⁴Angelucci E, Baronciani D. Allogeneic stem cell transplantation for thalassemia major. Haematologica. 2008;93:1780. ⁵Shenoy S, Walters MC, Ngwube A, et al. Unrelated donor transplantation in children with thalassemia using reduced-intensity conditioning: The URTH Trial. Biol Blood Marrow Transplant. 2018;24:1216–1222. ⁶See WSQ, Tung JYL, Cheuk DKL, et al. Endocrine complications in patients with transfusion-dependent thalassaemia after haemopoietic stem cell transplantation. Bone Marrow Transplant. 2018;53:356–360.

While the criteria from the above classification are still relevant, currently, outcomes of HSCT in thalassemia are mostly dependent on two critical considerations: (a) the characteristics of the donor and (b) the preexisting morbidities in the recipient. The outcomes are superior when the donor is a matched relative, typically a sibling. Although other donor types have been used in the clinical trial set ting, outcomes are inferior from matched unrelated donors or any mis matched donor, including a haploidentical donor. However, over the years, results have improved quite significantly. In view of the available evidence, stem cell transplantation from a partially human leukocyte antigen (HLA)-matched relative is not routinely advisable, although it may be considered in extreme situations when transfusion support is impossible or life threatening when a patient is completely noncompliant with any type of iron chelation therapy. Additionally, alternative donor sources such as umbilical cord blood also have been used with some success, but because of the limited number of stem cells in each cord blood unit, this is limited to smaller children. Preexisting morbidities such as hepatomegaly, with or without fibrosis, and severe (inadequately treated) iron overload, increase the risk of failure.

Stem cell transplantation can fail or be lethal owing to its immunologic complications. The complications related to the procedure are similar to those that would occur in other allogeneic transplants and are related to preparative myeloablative chemotherapy, the risk of infection during the neutropenic period prior to engraftment, the occurrence of graft-versus-host disease (GVHD), and loss of the graft. The overall incidence of acute GVHD is 17% to 32% depending on the prophylaxis regimen, and the incidence of chronic GVHD is 27% in patients receiving hematopoietic stem cells from an HLA-matched parent or sibling.  In addition, side effects, such as infertility and clonal disease from the conditioning chemotherapy, are sometimes deterrents for patients who are seeking a curative approach.

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Thalassemic Structural Variants

Chronic Care of the Adult Patient With Thalassemia : Novel Therapeutic Approaches

Survival in Patients With Thalassemia Major

Organ System Manifestations of Hypothyroidism: Haematological Changes

Organ System Manifestations of Hypothyroidism: Musculoskeletal Changes

Organ System Manifestations of Hypothyroidism: Cerebral and neurological Changes

Organ System Manifestations of Hypothyroidism: Respiratory Changes

Organ System Manifestations of Hypothyroidism: Cardiovascular Changes

Organ System Manifestations of Hypothyroidism : Cutaneous Manifestations and Changes in the Connective Tissues

Thromboembolic Conditions

Conditions that Cause Excessive Bleeding in Humans

Absent Intrinsic Factor Secretion and Pernicious Anemia