T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Shah, Ravi M.¹  Elfeky, Reem³  Nademi, Zohreh¹  Qasim, Waseem³  Amrolia, Persis³  Chiesa, Robert³  Rao, Kanchan³  Lucchini, Giovanna³  Silva, Juliana M. F.³  Worth, Austen³  Barge, Dawn⁴  Ryan, David⁴  Conn, Jane⁵  Cant, Andrew J.¹  Skinner, Roderick²  Abd Hamid, Intan Juliana¹  Flood, Terence¹  Abinun, Mario¹  Hambleton, Sophie¹  Gennery, Andrew R.¹  Veys, Paul³  Slatter, Mary¹ 

[1] Great North Childrens Hosp, Royal Victoria Infirm, Dept Immunol & BMT, Newcastle Upon Tyne, Tyne & Wear, England

[2] Great North Childrens Hosp, Royal Victoria Infirm, Dept Paediat Oncol & BMT, Newcastle Upon Tyne, Tyne & Wear, England

[3] Great Ormond St Hosp Children NHS Fdn Trust, Dept Immunol & BMT, London, England

[4] Newcastle Tyne Hosp Natl Hlth Serv Trust, Immunol Lab, Newcastle Upon Tyne, Tyne & Wear, England

[5] Northern Ctr Canc Care, Dept Haematooncol, Newcastle Upon Tyne, Tyne & Wear, England

关键词: Primary immunodeficiency;    haploidentical;    mismatched unrelated;    hematopoietic stem cell transplantation;    CD3(+) T-cell receptor alpha beta(+) cell depletion;   

DOI  :  10.1016/j.jaci.2017.07.008

来源: Elsevier

【 摘 要 】

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) alpha beta CD3(+) cells from the graft. Methods: CD3(+)TCR alpha beta(+)/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(+)TCR alpha beta(+) and CD19(+) cell-depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.

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