Hematologic responses to fetal globin gene inducers or erythropoietin (EPO) in β-thalassemia patients.
| Therapeutic Agent . | Action . | Thalassemia Syndromes . | Increase in Total Hb (g/dL) [range] . | Responses . | Authors . |
|---|---|---|---|---|---|
| Abbreviations: SCFAD, short chain fatty acid derivative, HDACi, histone deacetylase inhibitor; AC, acetyl group; R, repressor; SSP, stage selector protein(s); BFU-E, burst forming units erythroid | |||||
| 5-Azacytidine | Hypomethylation +/− cytotoxicity | Thalassemia intermedia | 2.5 [1.5–4] | 1/1 | Ley 19823 |
| 1/1 | Dunbar 19894 | ||||
| 3/3 | Lowrey 19935 | ||||
| Hydroxyurea (HU) | Cytotoxicity and erythroid regeneration →high-F BFU-E | HbE/β-thalassemia | 2.0 [1–3.3] | 3/3 | Hajjar 19946 |
| 2.7 [2.2–3.2] | 2/2 (β globin) | Zeng 19957 | |||
| 0.6 [0–1.7] | 11/13 | Fucharoen 19968 | |||
| Thalassemia intermedia | 1.0 | 3/8 | Loukopoulos 19989 | ||
| HbE/β-thalassemia | 0.9 | 7/19 | Singer 200210 | ||
| Sodium phenylbutyrate (SPB) | ? HDACi effect | Thalassemia intermedia and major | 2.1 [1.2–2.8] | 4/8 untransfused | Collins 199511 |
| Arginine butyrate (AB) and AB + Erythropoietin (EPO) | Activates γ globin gene promoter, (SSP binding), (? HDACi effect) | Thalassemia intermedia and major | 2.7 [0.6–5] | 7/10 (AB +/− EPO) | Perrine 199312 Perrine 200313 |
| Isobutyramide | Activates γ globin gene promoter | Thalassemia intermedia | Increase in HbF, Reduced transfusion requirements | 6/10 | Cappellini, 20002 |
| Thalassemia major | 2/4 | Reich 200014 | |||
| EPO | Stimulates erythroid proliferation, promotes erythroid cell survival | Thalassemia intermedia | 2 [1–3] | 5–7/10 | Rachmilewitz 199815 |
| Thalassemia major | 2.5 | 4/4 | Bourantas 199716 | ||
| 2 | 8/10 | Nisli 199617 | |||
| Reduced transfusion requirements | 3/26 | Nisli 199718 | |||
| 5/10 | Chaidos 200419 | ||||
| Darbepoietin | Stimulates erythropoiesis | Thalassemia intermedia | 1.6 [0.7–3.8] | 4/6 | Singer 200320 |
| HU + EPO | As above | Thalassemia intermedia | 1.7 [0.5–4] | Loukopoulos 19989 | |
| HbE/β-thalassemia | 1.2 | 1/5 | Singer 200210 | ||
| HU + SPB | As above | β Lepore | 3 [2–4] | 2/2 | Olivieri 199721 |
| Therapeutic Agent . | Action . | Thalassemia Syndromes . | Increase in Total Hb (g/dL) [range] . | Responses . | Authors . |
|---|---|---|---|---|---|
| Abbreviations: SCFAD, short chain fatty acid derivative, HDACi, histone deacetylase inhibitor; AC, acetyl group; R, repressor; SSP, stage selector protein(s); BFU-E, burst forming units erythroid | |||||
| 5-Azacytidine | Hypomethylation +/− cytotoxicity | Thalassemia intermedia | 2.5 [1.5–4] | 1/1 | Ley 19823 |
| 1/1 | Dunbar 19894 | ||||
| 3/3 | Lowrey 19935 | ||||
| Hydroxyurea (HU) | Cytotoxicity and erythroid regeneration →high-F BFU-E | HbE/β-thalassemia | 2.0 [1–3.3] | 3/3 | Hajjar 19946 |
| 2.7 [2.2–3.2] | 2/2 (β globin) | Zeng 19957 | |||
| 0.6 [0–1.7] | 11/13 | Fucharoen 19968 | |||
| Thalassemia intermedia | 1.0 | 3/8 | Loukopoulos 19989 | ||
| HbE/β-thalassemia | 0.9 | 7/19 | Singer 200210 | ||
| Sodium phenylbutyrate (SPB) | ? HDACi effect | Thalassemia intermedia and major | 2.1 [1.2–2.8] | 4/8 untransfused | Collins 199511 |
| Arginine butyrate (AB) and AB + Erythropoietin (EPO) | Activates γ globin gene promoter, (SSP binding), (? HDACi effect) | Thalassemia intermedia and major | 2.7 [0.6–5] | 7/10 (AB +/− EPO) | Perrine 199312 Perrine 200313 |
| Isobutyramide | Activates γ globin gene promoter | Thalassemia intermedia | Increase in HbF, Reduced transfusion requirements | 6/10 | Cappellini, 20002 |
| Thalassemia major | 2/4 | Reich 200014 | |||
| EPO | Stimulates erythroid proliferation, promotes erythroid cell survival | Thalassemia intermedia | 2 [1–3] | 5–7/10 | Rachmilewitz 199815 |
| Thalassemia major | 2.5 | 4/4 | Bourantas 199716 | ||
| 2 | 8/10 | Nisli 199617 | |||
| Reduced transfusion requirements | 3/26 | Nisli 199718 | |||
| 5/10 | Chaidos 200419 | ||||
| Darbepoietin | Stimulates erythropoiesis | Thalassemia intermedia | 1.6 [0.7–3.8] | 4/6 | Singer 200320 |
| HU + EPO | As above | Thalassemia intermedia | 1.7 [0.5–4] | Loukopoulos 19989 | |
| HbE/β-thalassemia | 1.2 | 1/5 | Singer 200210 | ||
| HU + SPB | As above | β Lepore | 3 [2–4] | 2/2 | Olivieri 199721 |