Long Term Outcomes in β Thalassemia Major

Hematopoietic stem cell transplantation (HSCT) is considered a suitable alternative to conservative management which includes chronic transfusion therapy, iron chelation (iron overload) and management of complications of transfusion therapy and iron overload. Barriers to HSCT considerations include risks inherent to transplant- early mortality, graft versus host disease (GVHD), graft rejection, infections prior to immune reconstitution, and transplant related organ toxicities. As in supportive care, significant progress has been made in HSCT for thalassemia has been made over the last 3 decades. This has resulted in disease-free survival (DFS) rates exceeding 80% especially in young, low-risk patients with histocompatible (same gene) family donors and more recently even in unrelated donor transplants following streamlining of preparative regimen and improvements in post-HSCT supportive care. Lucarelli and his colleagues at Pesaro initially pioneered HSCT in thalassemia and described a standard "Pesaro" risk stratification scheme based on liver size by physical examination, fibrosis detected on liver biopsy, and chelation history. This has been used for years to risk stratify patients before HSCT and has been shown to correlate well with immediate transplantation outcomes. More recently reports from the Center for International Blood and Marrow Transplant Research (CIBMTR) and from the Asian sub-continent on results of Human Leukocyte Antigen (HLA) -matched sibling HSCT for thalassemia major confirmed that age at transplantation and liver size are independent predictors of mortality after transplantation. In patients aged \<7 years and without hepatomegaly (liver palpated \<2 cm below the costal margin), the 5-year probabilities of Overall Survival (OS) and DFS were 98% and 94%, respectively (ref). Morbidity in thalassemia patients (both transplant related and non-transplanted) is attributed to iron overload associated end organ damage. Although there is data on long term outcomes in chronically transfused thalassemia patients, the data on long-term outcomes after HSCT for thalassemia remains limited. Some patients undergo hematopoietic stem cell transplantation (HSCT) in hopes to cure themselves of Beta-Thalassemia. Other patients manage their Beta-Thalassemia with supportive care including chronic blood transfusions, iron chelation and medications. The purpose of this study is to compare how patients with Beta-Thalassemia are doing after HSCT versus those patients who manage their Beta-Thalassemia with supportive care. This proposal aims to compare long term outcomes in thalassemia patients that have survived a HSCT for thalassemia and compare it with the age and sex matched patients who have remained on transfusion therapy with regular chelation. In order to compare these two subsets of patients, data will be obtained from the Thalassemia Longitudinal Cohort (TLC) study.