Ravi M Shah1, Reem Elfeky2, Zohreh Nademi3, Waseem Qasim2, Persis Amrolia2, Robert Chiesa2, Kanchan Rao2, Giovanna Lucchini2, Juliana M F Silva2, Austen Worth2, Dawn Barge4, David Ryan4, Jane Conn5, Andrew J Cant3, Roderick Skinner6, Intan Juliana Abd Hamid3, Terence Flood3, Mario Abinun3, Sophie Hambleton3, Andrew R Gennery3, Paul Veys2, Mary Slatter3. 1. Department of Immunology and BMT, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. Electronic address: rshah_haemonc@yahoo.ca. 2. Departments of Immunology and BMT, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 3. Department of Immunology and BMT, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. 4. Immunology Laboratory, Newcastle upon Tyne Hospitals National Health Service Trust, Newcastle upon Tyne, United Kingdom. 5. Department of Haemato-Oncology, Northern Center for Cancer Care, Newcastle upon Tyne, United Kingdom. 6. Department of Paediatric Oncology and BMT, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
Abstract
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) αβ CD3+ cells from the graft. METHODS: CD3+TCRαβ+/CD19+ depleted grafts were given in conditioned (except 3) children with PIDs. Treosulfan (busulfan in 1 patient), fludarabine, thiotepa, and anti-thymocyte globulin or alemtuzumab conditioning were used in 77% of cases, and all but 4 received GvHD prophylaxis. RESULTS: Twenty-five patients with 12 types of PIDs received 26 HSCTs. Three underwent transplantation for refractory GvHD that developed after the first cord transplantation. At a median follow-up of 20.8 months (range, 5 month-3.3 years), 21 of 25 patients survived and were cured of underlying immunodeficiency. Overall and event-free survival at 3 years were 83.9% and 80.4%, respectively. Cumulative incidence of grade II to IV acute GvHD was 22% ± 8.7%. No case of visceral or chronic GvHD was seen. Cumulative incidences of graft failure, cytomegalovirus, and/or adenoviral infections and transplant-related mortality at 1 year were 4.2% ± 4.1%, 58.8% ± 9.8%, and 16.1% ± 7.4%, respectively. Patients undergoing transplantation with systemic viral infections had poor survival in comparison with those with absent or resolved infections (33.3% vs 100%). CONCLUSION: CD3+TCRαβ+ and CD19+ cell-depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD-causing T-cell receptor (TCR) αβ CD3+ cells from the graft. METHODS: CD3+TCRαβ+/CD19+ depleted grafts were given in conditioned (except 3) children with PIDs. Treosulfan (busulfan in 1 patient), fludarabine, thiotepa, and anti-thymocyte globulin or alemtuzumab conditioning were used in 77% of cases, and all but 4 received GvHD prophylaxis. RESULTS: Twenty-five patients with 12 types of PIDs received 26 HSCTs. Three underwent transplantation for refractory GvHD that developed after the first cord transplantation. At a median follow-up of 20.8 months (range, 5 month-3.3 years), 21 of 25 patients survived and were cured of underlying immunodeficiency. Overall and event-free survival at 3 years were 83.9% and 80.4%, respectively. Cumulative incidence of grade II to IV acute GvHD was 22% ± 8.7%. No case of visceral or chronic GvHD was seen. Cumulative incidences of graft failure, cytomegalovirus, and/or adenoviral infections and transplant-related mortality at 1 year were 4.2% ± 4.1%, 58.8% ± 9.8%, and 16.1% ± 7.4%, respectively. Patients undergoing transplantation with systemic viral infections had poor survival in comparison with those with absent or resolved infections (33.3% vs 100%). CONCLUSION: CD3+TCRαβ+ and CD19+ cell-depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.
Authors: Mathias Kurzay; Fabian Hauck; Irene Schmid; Volker Wiebking; Anna Eichinger; Eva Jung; Ann Boekstegers; Tobias Feuchtinger; Christoph Klein; Michael H Albert Journal: Haematologica Date: 2019-03-07 Impact factor: 9.941
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