Landmarks in development of allogeneic transplantation for thalassemia
| Reference . | Year . | Center . | Main donor population . | Recipients . | Innovation . | Key outcome . |
|---|---|---|---|---|---|---|
| 5 | 1990 | Pesaro, Italy | HLA-identical family donors | 222 TM age <16 y | First large series. Identification of class 1, 2, 3 risk conditioning: busulfan (3.5 mg/kg per d for 4 d) + cyclophosphamide (50 mg/kg per d for 4 d) | Class 1: mortality 6%, rejection 0% |
| Class 3: mortality 24%, rejection 35% | ||||||
| Sodani, Blood | 2004 | Rome, Italy | HLA-identical family donors | 33 TM: all class 3, age <17 y | Reduced C + add fludarabine Immunosuppression with azathioprine chelation. Hydroxyurea to suppress BM (from day 45) | All class 3: mortality 7%, rejection 8% |
| Andreani, Blood Transf | 2008 | Rome, Italy | HLA-identical sibling donor | 93 TM median age 9.2 y | Stable mixed chimerism in mature erythrocytes Standard Bu, Cy conditioning plus: ±fludarabine, hydroxyurea, and azathioprine | Stable mixed chimerism in 46% of patients. Residual host cells increase rejection risk |
| Gaziev, Blood | 2010 | Rome, Italy | HLA-identical family donor | 71 children with liver damage | Pharmacokinetic monitoring of Bu | 7% mortality, 5% rejection; pharmacokinetic monitoring improves outcome |
| 7 | 2012 | Athens, Greece | HLA-matched siblings | 75 pediatric TM | ATG with conditioning to reduce graft rejection | Mortality 4%, rejection 4%, overall mortality 6%, class 3 |
| Galambrun, Biol Blood Marrow Transplant | 2013 | France, multicenter | Mainly matched sibling 96/108 | 108: TM | ATG to reduce graft rejection | 35% rejection without ATG 10% rejection with ATG |
| Mathews, Blood | 2013 | Vellore, India | Matched related donors | 50 high-risk TM (class 3) | Treosulfan-based conditioning | Mortality 13%, rejection 8% |
| 8 | 2005 | Cagliari, Italy BMT Group | MUD | 27 TM adults; median age, 22 y | High-resolution HLA molecular type conditioning: addition of thiotepa to Bu, Cy | Mortality 21%, rejection 14% |
| Li, Blood | 2012 | Guangzhou, China | 52 MUD, 30 matched sibling donors | 82 TM children and adolescents | Conditioning modifications: Bu adjusted to PK fludarabine 200 mg/kg, thiotepa, azathioprine + Hu on days −45 to −11 | Mortality 9%, rejection 4% with MUD novel conditioning improves survival in MUD |
| 24 | 2012 | Rome, Italy | MUD (n = 40) HLA-identical sibling (n = 20) | Children and adults median 7 y, classes 1-3 | Conditioning with treosulfan + thiotepa and fludarabine to reduce toxicity | Mortality 7%, rejection 9%; treosulfan-based regimen effective and safe |
| Ruggeri, Biol Blood Marrow Transplant | 2011 | Paris, France, Eurocord office | Cord umbilical unrelated | 35 children with TM | Unrelated umbilical cord | Mortality 38%, rejection 57%; low cell dose associated with graft failure |
| Sodani, Blood | 2010 | Rome, Italy | HLA-haploidentical maternal donors | 22 TM children and adults | T depleted CD34+ donation | Mortality 10%, rejection 27%; no GVHD in those with full chimerism (n = 14) |
| Gaziev, Blood Adv | 2018 | Rome, Italy | HLA-haploidentical family donors | 14 TM (TCR) 40 TM CD34+ comparators | TCRαβ+/CD19+-depleted grafts (TCR) ATG containing preparative regimen | Mortality 16% in TCR group, rejection 14%; lymphoproliferative complications, thrombocytopenia, hemolytic anemia |
| Reference . | Year . | Center . | Main donor population . | Recipients . | Innovation . | Key outcome . |
|---|---|---|---|---|---|---|
| 5 | 1990 | Pesaro, Italy | HLA-identical family donors | 222 TM age <16 y | First large series. Identification of class 1, 2, 3 risk conditioning: busulfan (3.5 mg/kg per d for 4 d) + cyclophosphamide (50 mg/kg per d for 4 d) | Class 1: mortality 6%, rejection 0% |
| Class 3: mortality 24%, rejection 35% | ||||||
| Sodani, Blood | 2004 | Rome, Italy | HLA-identical family donors | 33 TM: all class 3, age <17 y | Reduced C + add fludarabine Immunosuppression with azathioprine chelation. Hydroxyurea to suppress BM (from day 45) | All class 3: mortality 7%, rejection 8% |
| Andreani, Blood Transf | 2008 | Rome, Italy | HLA-identical sibling donor | 93 TM median age 9.2 y | Stable mixed chimerism in mature erythrocytes Standard Bu, Cy conditioning plus: ±fludarabine, hydroxyurea, and azathioprine | Stable mixed chimerism in 46% of patients. Residual host cells increase rejection risk |
| Gaziev, Blood | 2010 | Rome, Italy | HLA-identical family donor | 71 children with liver damage | Pharmacokinetic monitoring of Bu | 7% mortality, 5% rejection; pharmacokinetic monitoring improves outcome |
| 7 | 2012 | Athens, Greece | HLA-matched siblings | 75 pediatric TM | ATG with conditioning to reduce graft rejection | Mortality 4%, rejection 4%, overall mortality 6%, class 3 |
| Galambrun, Biol Blood Marrow Transplant | 2013 | France, multicenter | Mainly matched sibling 96/108 | 108: TM | ATG to reduce graft rejection | 35% rejection without ATG 10% rejection with ATG |
| Mathews, Blood | 2013 | Vellore, India | Matched related donors | 50 high-risk TM (class 3) | Treosulfan-based conditioning | Mortality 13%, rejection 8% |
| 8 | 2005 | Cagliari, Italy BMT Group | MUD | 27 TM adults; median age, 22 y | High-resolution HLA molecular type conditioning: addition of thiotepa to Bu, Cy | Mortality 21%, rejection 14% |
| Li, Blood | 2012 | Guangzhou, China | 52 MUD, 30 matched sibling donors | 82 TM children and adolescents | Conditioning modifications: Bu adjusted to PK fludarabine 200 mg/kg, thiotepa, azathioprine + Hu on days −45 to −11 | Mortality 9%, rejection 4% with MUD novel conditioning improves survival in MUD |
| 24 | 2012 | Rome, Italy | MUD (n = 40) HLA-identical sibling (n = 20) | Children and adults median 7 y, classes 1-3 | Conditioning with treosulfan + thiotepa and fludarabine to reduce toxicity | Mortality 7%, rejection 9%; treosulfan-based regimen effective and safe |
| Ruggeri, Biol Blood Marrow Transplant | 2011 | Paris, France, Eurocord office | Cord umbilical unrelated | 35 children with TM | Unrelated umbilical cord | Mortality 38%, rejection 57%; low cell dose associated with graft failure |
| Sodani, Blood | 2010 | Rome, Italy | HLA-haploidentical maternal donors | 22 TM children and adults | T depleted CD34+ donation | Mortality 10%, rejection 27%; no GVHD in those with full chimerism (n = 14) |
| Gaziev, Blood Adv | 2018 | Rome, Italy | HLA-haploidentical family donors | 14 TM (TCR) 40 TM CD34+ comparators | TCRαβ+/CD19+-depleted grafts (TCR) ATG containing preparative regimen | Mortality 16% in TCR group, rejection 14%; lymphoproliferative complications, thrombocytopenia, hemolytic anemia |
Bu, busulfan; Cy, cyclophosphamide; TM, thalassemia major.