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PubMed This is a summary of 28 peer-reviewed journal articles Updated
Hematology

Treatments and Therapies: Transfusions, Chelation, and Beyond

At a Glance

Treatment for HbE/beta-thalassemia is individualized: transfusions manage severe anemia, iron chelation removes excess iron, and luspatercept may reduce transfusion needs. Some patients may consider stem cell transplant or gene therapy, but these options require conditioning and long-term follow-up.

Managing HbE/beta-thalassemia requires a personalized approach that changes as you or your child grows. While standard treatments focus on maintaining healthy blood levels and managing iron, newer therapies are beginning to offer more options for reducing the burden of the disease.

The Foundation: Blood Transfusion Therapy

For those with the Transfusion-Dependent (TDT) phenotype, regular blood transfusions are the cornerstone of care [1].

  • The Goal: Transfusions do more than just treat anemia; they provide enough healthy red blood cells to tell the bone marrow it can stop working so hard. This helps prevent bone changes and organ enlargement [2][3].
  • Extended Matching: To prevent your immune system from forming antibodies that can cause hemolytic transfusion reactions (a process called alloimmunization), standard care now recommends extended red-cell matching. This goes beyond the basic ABO and RhD types to include other markers like Rh C, c, E, e and Kell [4][5]. Matching these antigens can significantly reduce the risk of developing harmful antibodies [6]. The blood bank coordinates this extended matching for every unit.

Managing Iron: Chelation Therapy

Every bag of blood contains iron that the body cannot easily get rid of. Even patients who don’t receive regular transfusions (NTDT) can develop iron overload because their bodies absorb extra iron from food to try and make more blood [7][8].

To remove this excess iron, doctors prescribe iron chelators. Note that chelation is not automatically required for every NTDT patient; decisions are individualized based on iron trends, liver iron concentration, and organ findings. Each medication requires specific safety monitoring:

  • Deferasirox (Exjade/Jadenu): Taken as a pill or granule. It requires monthly checks of kidney function (creatinine) and liver tests. Doctors also monitor for protein in the urine (proteinuria) because of the risk of renal and hepatic toxicity [9][10].
  • Deferiprone (Ferriprox): Requires strict white blood cell monitoring (absolute neutrophil count) because it can rarely cause a dangerous drop in infection-fighting cells called neutropenia or agranulocytosis. Action Plan: You must seek urgent medical advice for any fever, sore throat, or signs of infection [11].
  • Deferoxamine (Desferal): An older medication given via a slow pump under the skin. Long-term use requires regular hearing (audiology) and vision (ophthalmology) checks due to sensory toxicity risks [12][13].

New Horizons: Luspatercept

Luspatercept (Reblozyl) is a newer, non-curative injection that helps red blood cells mature more effectively [14].

  • For TDT: In many jurisdictions, it is indicated for adults to reduce the “transfusion burden” (the number of units needed), though it does not reliably eliminate the need for transfusions entirely [14].
  • For NTDT: It has been shown in trials to raise hemoglobin levels, which can improve energy, though pediatric and NTDT use depends on local approval and ongoing evidence [15][16].
    While it is an important tool, important risks include hypertension, bone pain, thromboembolic events, and potential worsening of extramedullary hematopoiesis [14].

Potentially Disease-Modifying and Intensive Options

For some families, therapies that offer a “functional cure” are considered. These options are intensive, carry significant risks, and eligibility depends on age, phenotype, and organ status.

  • Stem Cell Transplant (HSCT): Replacing the bone marrow with healthy cells from a donor (ideally a matched sibling). Risks include graft-versus-host disease (GVHD), severe infection, graft failure, and transplant-related mortality. It is most successful in younger children who haven’t yet developed organ damage from iron [17][18].
  • Gene Therapy: Newer “one-time” treatments use your own cells.
    • Exa-cel (Casgevy) uses CRISPR-based editing of a genetic enhancer to restart fetal hemoglobin [19].
    • Beti-cel (Zynteglo) is a lentiviral gene-addition therapy that introduces a functional beta-globin gene [20].
    • The Process: Both require myeloablative conditioning, a high-dose chemotherapy (busulfan) that clears out the old bone marrow to make room for the new cells [21][22].
    • The Risks: This chemotherapy can cause severe risks including prolonged cytopenias, infections, organ toxicity, and infertility, making fertility preservation (like freezing eggs or sperm) a vital step before starting [22][23].
    • Limitations: These therapies are extremely expensive and require specialized centers for treatment [24][25]. Long-term follow-up is necessary, and specific clinical efficacy for the HbE genotype continues to be established [26].

Regardless of the path chosen, regular monitoring of iron in the liver and heart through MRI remains essential to ensure the heart and other organs stay healthy for a lifetime [27][28].

Common questions in this guide

What are the main treatments for HbE/beta-thalassemia?
Treatment depends on whether a person is transfusion-dependent and on their anemia, iron levels, age, and organ health. Options include red blood cell transfusions, iron-removing medicines, luspatercept, and, for selected patients, a stem cell transplant or gene therapy.
What does extended blood matching mean, and why is it used?
The blood bank matches more blood markers than the basic ABO and RhD types, including Rh C, c, E, e, and Kell. This lowers the chance of developing antibodies that can make future transfusions unsafe or cause a reaction.
Does everyone with HbE/beta-thalassemia need iron chelation?
No. People who receive regular transfusions and some people who do not receive regular transfusions can build up excess iron, so the decision is based on iron trends, liver iron measurements, and signs of organ effects. A clinician chooses and monitors chelation for the individual.
What monitoring is needed with iron chelation medicines?
Deferasirox requires regular kidney and liver tests and checks for protein in the urine. Deferiprone requires frequent white blood cell monitoring, and fever or a sore throat needs urgent medical advice. Deferoxamine can require hearing and vision checks during long-term use.
Can luspatercept stop the need for transfusions?
Luspatercept may lower the number of transfusions needed by some adults with transfusion-dependent disease and may raise hemoglobin in some people who are not regularly transfused. It does not reliably eliminate transfusions, and approval and evidence vary by age, location, and disease group.
What should I know before gene therapy or a stem cell transplant?
Gene therapy requires intensive conditioning chemotherapy to clear space in the bone marrow, and transplant also involves major treatment and monitoring. Risks may include infections, low blood counts, organ injury, and infertility; transplant can also cause graft-versus-host disease or graft failure. Discuss fertility preservation, eligibility, long-term follow-up, and treatment at a specialized center with the care team.

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Has my child received extended red-cell genotyping (including C, c, E, e, and Kell) to help the blood bank find the safest possible matches?
  2. 2.What is the specific monitoring plan for my child's iron chelation medication—for example, how often will we check kidney function for deferasirox or white blood cell counts for deferiprone?
  3. 3.Based on my child's iron levels and current symptoms, would they be a candidate for luspatercept, and how likely is it to reduce their need for transfusions?
  4. 4.If we consider gene therapy or a stem cell transplant, what are the specific risks of the conditioning (chemotherapy) process, and how would we handle fertility preservation?
  5. 5.Are there local clinical trials for newer treatments like gene therapy that are specifically enrolling patients with the HbE/beta-thalassemia genotype?

References

References (28)
  1. 1

    The Effect of Blood Transfusion on Growth of Patients with Hb E/β-Thalassemia.

    Chuansumrit A, Sirachainan N, Kitpoka P, et al.

    Hemoglobin 2019; (43(4-5)):264-272 doi:10.1080/03630269.2019.1692863.

    PMID: 31760834
  2. 2

    New therapeutic targets in transfusion-dependent and -independent thalassemia.

    Cappellini MD, Motta I

    Hematology. American Society of Hematology. Education Program 2017; (2017(1)):278-283 doi:10.1182/asheducation-2017.1.278.

    PMID: 29222267
  3. 3

    Systematic Literature Review of the Burden of Disease and Treatment for Transfusion-dependent β-Thalassemia.

    Betts M, Flight PA, Paramore LC, et al.

    Clinical therapeutics 2020; (42(2)):322-337.e2 doi:10.1016/j.clinthera.2019.12.003.

    PMID: 31882227
  4. 4

    Alloimmunization in transfused patients with constitutional anemias in Norway.

    Furuseth MT, Alme C, Garvik LJ, et al.

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 2021; (60(5)):103257 doi:10.1016/j.transci.2021.103257.

    PMID: 34420880
  5. 5

    Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline.

    Compernolle V, Chou ST, Tanael S, et al.

    Transfusion 2018; (58(6)):1555-1566 doi:10.1111/trf.14611.

    PMID: 29697146
  6. 6

    Red blood cell alloimmunisation in transfusion-dependent thalassaemia: a systematic review.

    Franchini M, Forni GL, Marano G, et al.

    Blood transfusion = Trasfusione del sangue 2019; (17(1)):4-15 doi:10.2450/2019.0229-18.

    PMID: 30653458
  7. 7

    Precision Medicine in Transfusion-Dependent and Non-Transfusion-Dependent β-Thalassemia: Toward Personalized Diagnosis and Therapy.

    Karen AA, Tluli O, Hashem IE, et al.

    Hemoglobin 2026; (50(5)):405-413 doi:10.1080/03630269.2026.2709700.

    PMID: 42572810
  8. 8

    PREVALENCE AND RISK FACTORS FOR CARDIAC IRON OVERLOAD AND CARDIOVASCULAR COMPLICATIONS AMONG PATIENTS WITH THALASSEMIA IN NORTHERN THAILAND.

    Tantiworawit A, Tapanya S, Phrommintikul A, et al.

    The Southeast Asian journal of tropical medicine and public health 2016; (47(6)):1335-42.

    PMID: 29634199
  9. 9

    Jadenu® Substituting Exjade® in Iron Overloaded β-Thalassemia Major (BTM) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles.

    Yassin MA, Soliman AT, De Sanctis V, et al.

    Mediterranean journal of hematology and infectious diseases 2018; (10(1)):e2018064 doi:10.4084/MJHID.2018.064.

    PMID: 30416696
  10. 10

    Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST).

    Vichinsky E, El-Beshlawy A, Al Zoebie A, et al.

    Pediatric blood & cancer 2017; (64(9)) doi:10.1002/pbc.26507.

    PMID: 28296163
  11. 11

    Deferiprone versus deferoxamine in thalassemia intermedia: Results from a 5-year long-term Italian multicenter randomized clinical trial.

    Calvaruso G, Vitrano A, Di Maggio R, et al.

    American journal of hematology 2015; (90(7)):634-8 doi:10.1002/ajh.24024.

    PMID: 25809173
  12. 12

    Ocular manifestations in patients with transfusion-dependent β-thalassemia.

    Akritidou F, Praidou A, Papamitsou T, et al.

    Hippokratia 2021; (25(2)):79-82.

    PMID: 35937508
  13. 13

    Assessing the auditory effects of oral chelation therapy drug Deferasirox in individuals with β-thalassemia major.

    Tiwana BS, Aggarwal A, Bhagat S, et al.

    World journal of otorhinolaryngology - head and neck surgery 2024; (10(4)):309-314 doi:10.1002/wjo2.150.

    PMID: 39677049
  14. 14

    A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia.

    Cappellini MD, Viprakasit V, Taher AT, et al.

    The New England journal of medicine 2020; (382(13)):1219-1231 doi:10.1056/NEJMoa1910182.

    PMID: 32212518
  15. 15

    Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial.

    Taher AT, Cappellini MD, Kattamis A, et al.

    The Lancet. Haematology 2022; (9(10)):e733-e744 doi:10.1016/S2352-3026(22)00208-3.

    PMID: 36007538
  16. 16

    Efficacy and safety of luspatercept in non-transfusion-dependent β-thalassemia: long-term results from the BEYOND study.

    Taher AT, Viprakasit V, Kattamis A, et al.

    Blood advances 2025; (9(23)):6108-6119 doi:10.1182/bloodadvances.2025016554.

    PMID: 40875596
  17. 17

    Unrelated Donor Peripheral Blood Stem Cell Transplantation for Patients with β-Thalassemia Major Based on a Novel Conditioning Regimen.

    Sun L, Wang N, Chen Y, et al.

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2019; (25(8)):1592-1596 doi:10.1016/j.bbmt.2019.03.028.

    PMID: 30951841
  18. 18

    Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

    Rahal I, Galambrun C, Bertrand Y, et al.

    Haematologica 2018; (103(7)):1143-1149 doi:10.3324/haematol.2017.183467.

    PMID: 29599204
  19. 19

    Gene Therapies for Hemoglobinopathies: Efficacy, Cell Collection & Transfusion Support.

    Inam Z, Han H, Webb J, Delaney M

    Transfusion medicine reviews 2025; (39(4)):150930 doi:10.1016/j.tmrv.2025.150930.

    PMID: 41223813
  20. 20

    Regulatory Assessment of Casgevy for the Treatment of Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-Occlusive Crises.

    Kerwash E, Sajic M, Rantell KR, et al.

    Current issues in molecular biology 2024; (46(8)):8209-8225 doi:10.3390/cimb46080485.

    PMID: 39194702
  21. 21

    Exa-cel in Children with Transfusion-Dependent β-Thalassemia or Sickle Cell Disease.

    Frangoul H, de la Fuente J, Chopra Y, et al.

    The New England journal of medicine 2026; (395(10)):947-958 doi:10.1056/NEJMoa2603387.

    PMID: 42274009
  22. 22

    Alternative conditioning regimens for hemoglobinopathy gene therapy: balancing efficacy, toxicity, and the next frontier.

    Sharma A, Corbacioglu S

    Blood advances 2026; (10(18)):6118-6123 doi:10.1182/bloodadvances.2026019856.

    PMID: 42418372
  23. 23

    Hurdles to the Adoption of Gene Therapy as a Curative Option for Transfusion-Dependent Thalassemia.

    Thuret I, Ruggeri A, Angelucci E, Chabannon C

    Stem cells translational medicine 2022; (11(4)):407-414 doi:10.1093/stcltm/szac007.

    PMID: 35267028
  24. 24

    Current therapeutic landscape of β-thalassemia: focus on gene therapy.

    Cheng AN, Kwiatkowski JL

    Therapeutic advances in rare disease 2026; (7()):26330040261433028 doi:10.1177/26330040261433028.

    PMID: 41919270
  25. 25

    Translating CRISPR to Practice in the Clinic: Transformative Therapy in Hemoglobinopathies and Emerging Applications in Malignancies.

    Salim Hammoud M, Hanna R

    JCO oncology practice 2026; OP2600479 doi:10.1200/OP-26-00479.

    PMID: 42617141
  26. 26

    Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia.

    Locatelli F, Lang P, Wall D, et al.

    The New England journal of medicine 2024; (390(18)):1663-1676 doi:10.1056/NEJMoa2309673.

    PMID: 38657265
  27. 27

    Severe Liver Iron Concentrations (LIC) in 24 Patients with β-Thalassemia Major: Correlations with Serum Ferritin, Liver Enzymes and Endocrine Complications.

    Kanbour I, Chandra P, Soliman A, et al.

    Mediterranean journal of hematology and infectious diseases 2018; (10(1)):e2018062 doi:10.4084/MJHID.2018.062.

    PMID: 30416694
  28. 28

    Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent β-thalassemia patients who remained on the same monotherapy over 10 years.

    Musallam KM, Barella S, Origa R, et al.

    Blood cells, molecules & diseases 2024; (107()):102859 doi:10.1016/j.bcmd.2024.102859.

    PMID: 38820707

This page is for informational purposes only and does not constitute medical advice. A hematology team should tailor transfusion, chelation, transplant, or gene-therapy decisions to the patient’s age, test results, and overall health.