T-cell receptor ??+ and CD19+ cell–depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency - 05/04/18
, Reem Elfeky, MD b, Zohreh Nademi, PhD a, Waseem Qasim, MD, PhD b, Persis Amrolia, PhD, FRCP, FRCPath b, Robert Chiesa, MD b, Kanchan Rao, MRCPCH b, Giovanna Lucchini, MD b, Juliana M.F. Silva, MD b, Austen Worth, MD, PhD b, Dawn Barge, PhD c, David Ryan, DipSc, MSc c, Jane Conn, MD d, Andrew J. Cant, MD a, Roderick Skinner, PhD, DCH, FRCPCH e, Intan Juliana Abd Hamid, MD a, Terence Flood, MD a, Mario Abinun, MD a, Sophie Hambleton, DPhil a, Andrew R. Gennery, MD a, Paul Veys, FRCP, FRCPath b, Mary Slatter, MD aAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Primary immunodeficiency, haploidentical, mismatched unrelated, hematopoietic stem cell transplantation, CD3+ T-cell receptor αβ+ cell depletion
Abbreviations used : aGvHD, ATG, CMV, CTL, EFS, GvHD, HHV-6, HSCT, mMUD, NK, PID, SCID, TCR, TMA, TPN
Plan
| Disclosure of potential conflict of interest: W. Qasim received consultancy fees from Orchard and Autolus and travel expenses from Miltenyi; his institution received grants from Bellicum and Miltenyi for other works; both the institution and the coauthor submitted a patent for T-cell gene editing; both received royalties from Orchard; and both received stock options from Autolus. A. Worth's institution received consultancy fees from advisory board work for Biotest, assessment of evidence of efficacy for cytomegalovirus specific IG, an NIHR grant for patient benefit and a grant from Welcome Trust Clinical research training Fellowship for other works; he personally received payment for manuscript preparation from the British Journal of Haematology for a commissioned review article. A. J. Cant received consultancy fees from Sanofi Pasteur MSD. S. Hambleton received board membership from MRC Infection and Immunity Board, is employed by Newcastle University, and received payment for lectures from Biotest Immunology forum; her institution received ad hoc consultancy fees from UCB Pharma and grants the from Sir Jules Thorn Charitable Trust and the Wellcome Trust for other works. P. Veys received payment for lectures from Gilead, Chimerix, and CIBMT. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 4
P. 1417 - avril 2018 Retour au numéro
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