Recent Advances in Bone Marrow Transplantation in Hemoglobinopathies

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is currently the only treatment with curative potential for sickle cell disease (SCD) and beta-thalassemia. HCT was first used to treat SCD and thalassemia more than two decades ago, and with increasing experience this treatment modality has shifted from being an experimental intervention to one in which selected patient populations are targeted for treatment. Recent multicenter clinical studies show an event-free survival (EFS) of 85% after human leukocyte antigen (HLA)-identical sibling transplantation for SCD, using conventional myeloablative conditioning with a backbone of busulfan (BU) and cyclophosphamide (CY) [1-3]. Results of HCT for thalassemia show very similar outcomes, with EFS probabilities that range from 81%-87% [4,5]. However, the risk of graft failure, recurrent disease, graft-versus-host-disease (GVHD), infections, and long-term sequelae of chronic GVHD and endocrinopathies related to Fe overload and myeloablative BU limit broader application of this therapy. Non-myeloablative conditioning regimens may offer a lower risk of toxicity, and investigations to identify a regimen that is sufficiently immunosuppressive to ensure stable engraftment of donor cells are ongoing. Alternative sources of donor hematopoietic cells that include HLA-matched unrelated donor (URD) and umbilical cord blood (UCB), are being pursued for hemoglobinopathies, with promising initial results. This review discusses the successes, challenges and future direction of HCT for SCD and thalassemia.

Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010

“…For example, patients' clinical conditions and transplantation events, such as causes of transplant-related mortality, were not detailed. Several experiences, such as those of North America and the FarEast, [14][15][16][17][18][19] were also not reported to the EBMT registry. However, the EBMT ProMISe regulations and the large number of cases reported guarantee the accuracy of the data presented.…”

Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia patients

“…This assumes major importance especially in developing countries that are unable to sustain the high-cost of prevention (prenatal diagnosis) and treatment (iron-chelation and frequent blood transfusion), let alone bone marrow transplantation (49). Novel therapeutic approaches, such as gene therapy (50,51), although of great potential, are not yet available, while the development of new symptom-ameliorating drugs is commercially unattractive due to the large investments required.…”

The Switch from Fetal to Adult Hemoglobin

“…The only potentially curative therapies that are available for these diseases are bone marrow transplantation (Michlitsch and Walters 2008) and gene therapy (Persons 2009), but there are numerous challenges that exist to implement these treatments and they have significant limitations for widespread use, particularly in the developing world (Sankaran and Nathan 2010b). These curative therapies still remain largely experimental, although important scientific and clinical advances in these approaches are being made (Hsieh et al 2009;Cavazzana-Calvo et al 2010).…”