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J Allergy Clin Immunol. 2018 Apr;141(4):1417-1426.e1. doi: 10.1016/j.jaci.2017.07.008. Epub 2017 Aug 3.

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

Author information

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.

Erratum in

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.

KEYWORDS:

CD3(+) T-cell receptor αβ(+) cell depletion; Primary immunodeficiency; haploidentical; hematopoietic stem cell transplantation; mismatched unrelated

PMID:
28780238
DOI:
10.1016/j.jaci.2017.07.008
[Indexed for MEDLINE]

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