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

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.

• Authors: Ravi M Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M F Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R Gennery, Paul Veys, Mary Slatter
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 141 Issue 4 Pg. 1417-1426.e1 (04 2018) ISSN: 1097-6825 [Electronic] United States
• PMID: 28780238 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Chemical References

• Antigens, CD19
• Antilymphocyte Serum
• CD19 molecule, human
• CD3 Complex
• Receptors, Antigen, T-Cell, alpha-beta
• Alemtuzumab
• Thiotepa
• treosulfan
• Vidarabine
• Busulfan
• fludarabine

Topics

• Alemtuzumab (immunology)
• Antigens, CD19 (immunology)
• Antilymphocyte Serum (immunology)
• Busulfan (analogs & derivatives, immunology)
• CD3 Complex (immunology)
• Child
• Child, Preschool
• Female
• Graft vs Host Disease (immunology, prevention & control)
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunologic Deficiency Syndromes (immunology, therapy)
• Infant
• Male
• Receptors, Antigen, T-Cell, alpha-beta (immunology)
• Retrospective Studies
• Thiotepa (immunology)
• Transplantation Conditioning (methods)
• Vidarabine (analogs & derivatives, immunology)