Allogeneic Hematopoietic Cell Transplant in β-Thalassemia Major

Abstract

β-Thalassemia major (BTM) occurs globally and represents a major growing health problem in many countries (Weatherall et al. 2010). BTM involves deficient or absent synthesis of the β-globin chains that constitute hemoglobin molecules and results in chronic hemolytic anemia. Subjects with BTM must adhere to continuous red blood cell replacement program to sustain life but unfortunately therapy comes with undesirable and sometimes life-threatening complications (Fung et al. 2006; Rahav et al. 2006). Without regular transfusions, BTM patients develop tremendous skeleton deformities, hepatomegaly, and splenomegaly from chronic hemolysis with expansion of the hematopoietic system, and as the disease advances, extramedullary hematopoiesis ensues (Sabloff et al. 2011; Angelucci et al. 2010). In addition, the patients usually incur cardiopulmonary problems from chronic anemia and iron overload. The only curative outlet from BTM is via deployment of allo-HCT preferably from HLA-matched sibling donor (MSD) early in the course of the disease. The pre-HCT chronic iron overload (plus its sequelae) and viral infection(s) must be medically managed even after successful allo-HCT in patient now referred to as “ex-thalassemics.” The basic concept behind allo-HCT is to substitute carefully selected HLA-MSD’s CD34+ hematopoietic cells with recipient “thalassemic clone” hematopoietic cells with a goal to achieve effective and sustainable hematopoiesis translated into transfusion independence. Evaluation prior to allo-HCT in younger children (<17 years of age) with BTM aims to allocate them in one of the three well-defined prognostic groups as defined in Pesaro classification; this classification coined by Lucarelli and colleagues also assists in selection of best allo-HCT program for each group. Older (>17 years of age) patients with BTM usually have organ damage due to higher degree of iron overload with increase incidence of graft rejection compared to younger children (Lucarelli G et al. 1999). Usually, BTM patients older than 17 years of age fall into “high-risk” category and are best served with more complex allo-HCT program, somewhat analogous to the transplant programs employed for younger children with Pesaro class 3 risk group (Lucarelli et al. 1992), although with less intensive conditioning regimen to minimize treatment-related mortality (TRM). It is prudent to acknowledge that in the current era and in the middle-high-income countries, morbidity and mortality of allo-HCT are challenged by the accomplishment of better survival rates with nontransplant approaches but these approaches offer no chance of a cure and in many cases persistence of lifelong complications. The discussion for and against allo-HCT should be carefully conducted in centers with expertise handling patients with BTM.