Reem Elfeky1, Ravi M Shah2, Mohamed N M Unni3, Giorgio Ottaviano4, Kanchan Rao5, Robert Chiesa5, Persis Amrolia6, Austen Worth5, Terry Flood3, Mario Abinun3, Sophie Hambleton3, Andrew J Cant3, Kimberly Gilmour5, Stuart Adams5, Gul Ahsan5, Dawn Barge3, Andrew R Gennery3, Waseem Qasim7, Mary Slatter3, Paul Veys6. 1. Molecular and Cellular Immunology Unit, University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Paediatric Allergy and Immunology, Ain Shams University, Cairo, Egypt. Electronic address: r.elfeky@ucl.ac.uk. 2. Blood and Bone Marrow Transplant Unit, Great Ormond Street Hospital, London, United Kingdom; Department of Paediatric Oncology and BMT, Alberta Children's Hospital, Calgary, Alberta, Canada. 3. Host Defence Unit, Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom. 4. Department of Paediatrics, Fondazione MBBM University of Milan-Bicocca, Monza, Italy. 5. Blood and Bone Marrow Transplant Unit, Great Ormond Street Hospital, London, United Kingdom. 6. Molecular and Cellular Immunology Unit, University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom; Blood and Bone Marrow Transplant Unit, Great Ormond Street Hospital, London, United Kingdom. 7. Molecular and Cellular Immunology Unit, University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom.
Abstract
BACKGROUND: Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks. OBJECTIVE: We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies. METHODS: Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) αβ/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34+ selection with T-cell add-back grafts, and 65 unmanipulated grafts. RESULTS: The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRαβ/CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRαβ+/CD19+-depleted and CB transplants versus 40% to 60% among the other groups. CONCLUSIONS: Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRαβ+/CD19+-depleted grafts produced comparable survival rates of around 80%, although with a high rate of aGvHD with the former and a high risk of viral reactivation with the latter that need to be addressed. Crown
BACKGROUND: Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks. OBJECTIVE: We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies. METHODS: Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) αβ/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34+ selection with T-cell add-back grafts, and 65 unmanipulated grafts. RESULTS: The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRαβ/CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRαβ+/CD19+-depleted and CB transplants versus 40% to 60% among the other groups. CONCLUSIONS: Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRαβ+/CD19+-depleted grafts produced comparable survival rates of around 80%, although with a high rate of aGvHD with the former and a high risk of viral reactivation with the latter that need to be addressed. Crown
Authors: Reem Elfeky; Giovanna Lucchini; Su-Han Lum; Giorgio Ottaviano; Natalia Builes; Zohreh Nademi; Alexandra Battersby; Terence Flood; Stephen Owens; Andrew J Cant; Helen Young; Sinéad Greener; Patrick Walsh; David Kavanagh; Srinivas Annavarapu; Kanchan Rao; Persis Amrolia; Robert Chiesa; Austen Worth; Claire Booth; Roderick Skinner; Bilyana Doncheva; Joseph Standing; Andrew R Gennery; Waseem Qasim; Mary Slatter; Paul Veys Journal: Blood Adv Date: 2020-06-09