Thalassemia is an inherited blood disorder that happens when the body doesn’t make enough healthy hemoglobin—a protein in your red blood cells that transports oxygen from your lungs to the rest of your body. When red blood cells do not have enough energy (ATP) within, they break down sooner than normal (called hemolysis) or don't mature properly (called ineffective erythropoiesis). This can lead to low hemoglobin, which results in chronic anemia. Signs and symptoms of thalassemia can vary from person to person. They may be present at birth or develop during the first 2 years of life. Some patients are diagnosed in adulthood. Some people don't have symptoms at all, while others need lifelong treatment.

Emerging Data

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Morbidity Data

QoL

Complications of chronic anemia develop over time^1,2

A 10-year cohort study of patients with non–transfusion-dependent (NTD) beta-thalassemia showed that, over time, hemoglobin is a significant predictor of morbidity.* Patients were morbidity-free at the start of observation and did not receive any form of transfusion, iron chelation, or fetal hemoglobin induction therapy over the 10-year study.¹

More than 86% of patients with hemoglobin less than 10 g/dL, and 21% of patients with hemoglobin more than or equal to 10 g/dL, experienced a morbidity.

Emerging data show patients with alpha-thalassemia may experience similar morbidities to patients with beta-thalassemia, including pulmonary hypertension, thrombotic events, osteoporosis, abnormal hepatic function, and endocrinopathy.^3-7

*Morbidities included are liver disease, extramedullary hematopoiesis, diabetes mellitus, hypothyroidism, hypoparathyroidism, osteoporosis, hypogonadism, thrombosis, and pulmonary hypertension.¹

^†Defined as hemoglobin levels <10 g/dL.²
^‡After adjusting for confounding/mediating effects of age, splenectomy, and serum ferritin.¹

The dataset consisted of 53 patients with beta-thalassemia intermedia who were from outside the US and had no existing morbidity at baseline. Mean baseline hemoglobin level was 9.1 ± 1.2 g/dL (range: 6.8–12.5) and median age was 24.7 years (range: 2–56). A total of 14 patients (26.9%) had a hemoglobin level ≥10 g/dL and 39 (73.1%) had a hemoglobin level <10 g/dL. No patients died or were lost to follow-up during the study.¹

Increases of 1 g/dL of hemoglobin are associated with reduced morbidity risk⁸

A 10-year retrospective cohort study of patients with NTD beta-thalassemia showed that a decrease of 1 g/dL of hemoglobin is independently associated with the development of morbidities. Baseline hemoglobin level and the number of new morbidities were collected for each patient.⁸

Graph showing how chronic anemia is associated with multiple morbidities.

Complications of thalassemia

The following complications were studied in one or both of two separate long-term studies^1,8:

Cardiovascular
- Heart failure
- Pulmonary hypertension
- Thrombosis

Endocrine and bone disease
- Osteoporosis
- Hypoparathyroidism
- Hypogonadism
- Diabetes mellitus

Leg ulcers

Hepatic
- Liver disease
- Abnormal liver function

Hematological
- Extramedullary hematopoietic pseudotumors

Cardiovascular
- Heart failure
- Pulmonary hypertension
- Thrombosis

Hepatic
- Liver disease
- Abnormal liver function

Endocrine and bone disease
- Osteoporosis
- Hypoparathyroidism
- Hypogonadism
- Diabetes mellitus

Hematological
- Extramedullary hematopoietic pseudotumors

Leg ulcers

In a retrospective analysis, data were obtained from 150 NTD patients with beta-thalassemia across 2 chronic care centers in Lebanon and Italy. The average hemoglobin level was taken at baseline based on an average over 6 months and the development of new morbidities was tracked over a 10-year follow-up period. These included established complications like extramedullary hematopoietic pseudotumor, leg ulcers, thrombosis, and more (pulmonary hypertension, abnormal liver function, heart failure, osteoporosis, hypogonadism, hypothyroidism, diabetes mellitus). All patients adhered to international screening guidelines.⁸

The mean age of patients was 35.7 ± 12.5 years (range: 8–66). The mean baseline hemoglobin level was 9.0 ± 1.4 g/dL (median: 8.7, range: 6.8–13.1) with 118 patients (78.7%) having levels <10 g/dL. No patients died, were lost to follow-up, or needed regular transfusions.⁸

PATIENTS WITH NTD THALASSEMIA REPORTED A SIMILAR OR WORSE QUALITY OF LIFE AS MEASURED BY SF-36 VS THOSE WHO WERE TRANSFUSION-DEPENDENT (TD)⁹

Differences between NTD and TD patients were clinically meaningful for vitality (energy and fatigue), mental health (psychological distress and well-being), and general health.⁹

Quality of life graph showing the mean difference of non–transfusion-dependent and transfusion-dependent patients.

No statistically significant differences were observed between the dark and light gray bars, which represent NTD and TD patients, respectively.⁹

Results were measured by the SF-36 questionnaire.^† Domains measured included⁹:

Vitality (eg, energy and fatigue)

General health

Mental health (eg, psychological distress and well-being)

Physical functioning (limitations in physical activities due to health problems)

Bodily pain

Social functioning (limitations in social activities due to physical or emotional problems)

Role-emotion (limitations in usual role activities due to emotional problems)

Role-function (limitations in usual role activities due to health problems)

Dataset was obtained from a multisite, prospective, non-interventional observational study conducted at 5 treatment centers across 4 countries: Greece, Italy, Lebanon, and Thailand, involving 102 adult patients with beta-thalassemia. Quality of life outcomes were collected using 2 validated patient-reported outcome (PRO) instruments: the 36-Item Short Form Survey version 2.0 (SF-36v2) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An). Data were collected at baseline and then once every 3 weeks for up to 24 weeks. The primary endpoints were the 2 summary scores of the SF-36v2, the Physical Component Score and Mental Component Score, for all patients with beta-thalassemia over the study period, compared with the general population. Secondary endpoints included changes in SF-36v2 and FACT-An scores between TD and NTD patients over the study period.⁹

Almost all health-related quality of life domain and summary scores were lower in patients who were NTD vs TD^9‡

^†SF-36 consists of 36 questions that are clustered to yield 8 health status scales. SF-36 score ranges from 0 to 100, with higher scores indicating higher levels of function and⁄or better health.¹⁰
^‡Role-physical was the only exception.⁹

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References:

1. Musallam KM, Cappellini MD, Daar S, Taher AT. Morbidity-free survival and hemoglobin level in non-transfusion dependent beta-thalassemia: a 10-year cohort study. Ann Hematol. 2022;101(1):203-204. doi:10.1007/s00277-020-04370-2 2. Musallam KM, Taher AT, Cappellini MD, et al. Untreated anemia in nontransfusion-dependent β-thalassemia: time to sound the alarm. European Hematology Association; 2022. 3. Musallam KM, Viprakasit V, Lombard L, et al. Systematic review and evidence gap assessment of the clinical, quality of life, and economic burden of alpha-thalassemia. eJHaem. Published online April 2, 2024. doi:10.1002/jha2.882 4. Amid, A, Angastiniotis, M, Boonbowornpong, TP, et al. Guidelines for the Management of α-Thalassaemia. Thalassaemia International Federation; 2023. 5. Musallam KM, Cappellini MD, Coates TD, et al. Alpha-thalassemia: a practical overview. Blood Rev. 2024;64:101165. doi:10.1016/j.blre.2023.101165 6. Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;11(10):1886-1892. doi:10.1182/blood-2009-09-243154 7. Winichakoon P, Tantiworwit A, Rattanathammethee T, et al. Prevalence and risk factors for complications in patients with nontransfusion dependent alpha- and beta-thalassemia. Anemia. 2015;2015. doi:10.1155/2015/793025 8. Musallam KM, Cappellini MD, Taher AT. Variations in hemoglobin level and morbidity burden in non-transfusion-dependent β-thalassemia. Ann Hematol. 2021;100(7):1903-1905. doi:10.1007/s00277-021-04456-5. 9. Cappellini MD, Kattamis A, Viprakasit V, et al. Quality of life in patients with β-thalassemia: a prospective study of transfusion-dependent and non-transfusion-dependent patients in Greece, Italy, Lebanon, and Thailand. Am J Hematol. 2019;94(10):E261-E264. doi:10.1002/ajh.25584 10. Short Form 36 (SF-36): an overview. ScienceDirect Topics. Accessed February 8, 2024. https://www.sciencedirect.com/topics/nursing-and-health-professions/short-form-36