Summary of patients who received allogeneic haematopoietic stem cell transplantation for alpha-thalassaemia.
| Patient no. | Age at HSCT/Sex | Mutation | IUT (Y/N) | Donor Source, Graft | Conditioning regimen | GVHD prophylaxis | Complications | Outcome | Authors |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 21 months/F | NA | N | MSD, BM | Bu,Cy, horse ATG | MTX, CSA | None | Neutrophil engraftment at day +17. Stable mixed chimerism (75%-90%). Transfusion independent. | Chik et al 1998 [46] |
| 2 | 21 months/F | Homozygous SEA deletion | N | MSD, 8/8 BM | Bu/Cy | CSA, MTX, horse ATG | None | Neutrophil engraftment at day +17. Donor chimerism 99%. Transfusion independent. | Chan et al (2021) [58] |
| 3 | 20 months/F | Homozygous SEA deletion | N | MSD, 5/6 CB | Bu/Cy | CSA, MTX, horse ATG | Grade 2 skin aGVHD resolved with systemic steroid, HHV−6 viremia resolved with foscarnet | Neutrophil engraftment at day +26. Donor chimerism 100%. Transfusion independent. | Chan et al (2021) [58] |
| 4 | 22 months/F | Homozygous SEA deletion | Y | MUD, 12/12 PBSC | Bu/Cy | CSA, MTX, horse ATG | Grade 2 aGVHD of skin and grade 3 aGVHD of gut resolved with systemic steroid, HHV−7 viremia spontaneously resolved | Neutrophil engraftment at day +15. Donor chimerism 100%. Transfusion independent. | Chan et al (2021) [58] |
| 5 | 28 months/M | Homozygous SEA deletion | Y | MUD, 12/12 PBSC | HU/AZA/Cy/Bu/T T/Flu | CSA, MTX, MMF, rabbit ATG | Grade 2 skin aGVHD resolved with systemic steroid, EBV and HHV−6 viremia resolved spontaneously.Line sepsis. | Neutrophil engraftment at day +11. Donor chimerism 98%. Transfusion independent. | Chan et al (2021) [58] |
| 6 | 60 months/M | Homozygous SEA deletion | Y | Haplo, PBSC (TCRαβ/CD45RA depleted) | HU/AZA/Cy/TT/Fl u/Treo | Rabbit ATG | Klebsiella bacteremia cleared with antibiotics. Grade 2 skin aGVHD resolved by topical steroid, grade 2 gut aGVHD resolved with steroid and ruxolitinib | Neutrophil engraftment at day +13. Donor chimerism 99%. Transfusion independent. | Chan et al (2021) [58] |
| 7 | 12 months/NA | NA | Y | MSD/NA | NA | NA | NA | Transfusion independent by 18 months | Kreger et al 2016 [2] |
| 8 | 24 months/NA | NA | N | NA | NA | NA | NA | Transfusion independent by 3 years | Kreger et al 2016 [2] |
| 9 | 20 months/F | Homozygous SEA deletion | N | MSD/CB | Bu/Cy/ATG | MTX,CSA | HHV-6 viremia, grade 2 skin aGVHD resolved with steroids, ITP resolved with IVIG. | Neutrophil engraftment at Day +26. Donor chimerism 100%. Transfusion independent. | Zhou et al 2001[59] |
| 10 | 23 months/M | Homozygous SEA deletion, Hb E trait | Y | MSD/BM | Cy/ 14Gy TBI | MTX, CSA | Mild VOD | Neutrophil engraftment at Day +27. Stable mixed donor chimerism 66%. Transfusion independent. | Thornley et al, 2003 [60] |
| 11 | 5 months/M | Homozygous deletion | Y | MUD, 10/10 BM | Bu/Cy/rabbit ATG | MTX, CSA | Moderate VOD treated with Antithrombin, Grade 4 mucositis, intubated x 18 days. | Neutrophil at Day +25. Stable mixed donor chimerism (78-95%). Transfusion independent. | ElSaid et al, 2016 [61] |
| 12 | 13 years/M | Homozygous SEA deletion | N | MMUD 9/10 | RIC (details NA) | NA | Invasive fungal infection, grade 4 skin and gut GVHD | Died 4 months post transplant from transplant related morbidity. | Pecker et al, 2016 [62] |
| 13 | 10 years/M | Homozygous SEA deletion | Y | MUD 9/10 | NA | NA | None | Donor 100% chimerism. Transfusion independent. | Pecker et al, 2016 [62] |
| 14 | 8 months/M | Homozygous SEA deletion | Y | #1 MUD, 4/6 CB | #1 Bu/Flu/ATG, TLI 750 cGy | #1 CSA, MMF | #1 Graft failure | #1 Graft failure | Yi et al, 2009 [63] |
| 2nd transplant at 18 months | #2 MUD, 6/6 CD34 selected PBSC | #2 Bu/Flu/ATG/TBI 200cGy | #2 CSA, MMF | #2 EBV associated PTLD treated with ganciclovir, Rituximab and reduced IS. No GVHD. | #2 Neutrophil engraftment at Day +18. Stable mixed donor chimerism 97%. Transfusion independent. | ||||
| 15 | 2 years/M | Homozygous SEA deletion | Y | MSD | Bu/Flu/ATG/TLI | NA | NA | Secondary graft failure at 7 months. Transfusion dependent. | Joshi et al, 2004 [64] |
| 16 | 44 months/F | Homozygous SEA deletion | N | MUD, 5/6 CB | Bu/Cy/horse ATG | Tacrolimus, MMF | Candida krusei sepsis, treated with liposomal amphotericin, grade 2 acute skin GVHD resolved with steroids. | Neutrophil engraftment at Day +12. Donor chimerism 100%. Transfusion independent. | Gumuscu et al, 2013 [65] |
| 17 | 19 months/F | Homozygous SEA deletion | N | MSD, BM | Bu/Cy | CSA, MTX | Febrile neutropenia, viral pneumonia, mucositis. | Neutrophil engraftment at Day +17. Mixed donor chimerism 59%. DLI x 5 then full donor chimerism achieved. Transfusion independent. | Pongtanakul et al, 2013 [66] |
NA: not available, HSCT: haematopoietic stem cell transplantation, IUT: intrauterine transfusions, GVHD: graft-versus-host-disease, F: female, M: male, SEA: Southeast Asian, MSD: matched sibling donor, MUD: matched unrelated donor, MMUD: mismatched unrelated donor, Haplo: haploidentical donor, BM: bone marrow, CB: cord blood, PBSC: peripheral blood stem cells, Bu: busulfan, Cy: cyclophosphamide, Hu: hydroxyurea, Aza: azathioprine, TT: thiotepa, Flu: fludarabine, Treo: treosulfan, CSA: cyclosporine, MTX: methotrexate, ATG: anti-thymocyte globulin, MMF: mycophenolate mofetil, aGVHD: acute graft-versus-host-disease, HHV-6: human herpes virus-6, EBV: Epstein-Barr virus, ITP: immune thrombocytopenia, IVIG: intravenous immunoglobulin, TBI: total body irradiation, VOD: veno-occlusive disease, Hb: haemoglobin, RIC: reduced intensity conditioning, TLI: total lymphoid irradiation, PTLD: post-transplant lymphoproliferative disease, ID: immunosuppression, DLI: donor lymphocyte infusion.
From: Chapter 12, CURATIVE THERAPIES FOR α-THALASSAEMIA
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