Evaluating People With Thalassemia: The Thalassemia Longitudinal Cohort (TLC) Study

Thalassemias are inherited blood disorders that are characterized by low levels of hemoglobin and healthy red blood cells. The two major types of thalassemia are alpha thalassemia and beta thalassemia, and there are several forms of each type. Symptoms can range from mild to severe and may include anemia, delayed growth, bone problems, and an enlarged spleen. People with mild forms of the disease may not need any treatment, while people with moderate to severe thalassemia may be treated with blood transfusions to refresh the healthy red blood cell supply, iron chelation therapy to remove excess iron from the body, and folic acid supplements to help build healthy red blood cells. Stem cell transplants can cure the disease, but they are not widely used because of the difficulty of finding donors. This study will establish a database of people with thalassemia and people who used to have thalassemia to examine the prevalence and incidence of complications related to the disease. Participants' DNA will be analyzed and plasma will be collected for use in future studies. Participants in this study may also be asked if they are interested in enrolling in other Thalassemia Clinical Research Network studies.

This study has enrolled people with thalassemia or people whose thalassemia was cured after undergoing a stem cell transplant. At a baseline study visit, participants with thalassemia will undergo a medical history interview; a medical record review; blood collection; and questionnaires on quality of life, nutritional status, and medication adherence. Follow-up visits will occur once a year for at least 3 years or for the duration of the study and will include repeat baseline testing. Participants who have undergone a successful stem cell transplant will attend only one study visit that will include a medical history interview, a medical record review, and quality of life questionnaires.

Inclusion criteria

for People with Thalassemia:

• Thalassemia, as documented by clinical diagnosis, including the following types:

• Beta-thalassemia (intermedia or major)
• Hemoglobin H (HbH) disease
• HbH with non-deletional mutations (e.g., HbH Constant Spring)
• E-beta-thalassemia
• Homozygous alpha-thalassemia (i.e., 4-gene alpha deletion or equivalent null alpha mutation)
• Other thalassemic conditions not explicitly excluded
• Thalassemia intermedia due to heterozygous beta mutation with alpha-gene excess
• Requires at least annual monitoring for end-organ injury related to thalassemia, including all clinical measures specified in this study

Inclusion criteria

for People who Have Received a Successful Stem Cell Transplant:

• Received a successful hematopoietic stem cell transplant, defined as engraftment of all three cell lines and transfusion independence by 100 days post-transplant, for any of the thalassemia disorders listed above
• Monitored for end-organ injury related to thalassemia before their successful stem cell transplant, including all clinical measures specified in this study

Exclusion criteria

for People with Thalassemia:

• Has any of the following mild or mixed diagnoses:

• Thalassemia trait (i.e., single recessive beta-gene mutation, two-gene alpha-gene mutation)
• Thalassemia/Hb S, C, or D compound heterozygotes
• HbH with steady state hemoglobin above 9.0 g/dL and no history of significant thalassemia complications (e.g., endocrinopathies, cardiac dysfunction, growth impairment, pulmonary hypertension)
• Unable or unwilling to be followed annually