New graft manipulation strategies improve the outcome of mismatched stem cell transplantation in children with primary immunodeficiencies.

Abstract

BACKGROUND:

Mismatched stem cell transplantation is associated with a high risk of graft loss, graft-versus-host disease (GvHD), and transplant-related mortality. Alternative graft manipulation strategies have been used over the last 11 years to reduce these risks.

OBJECTIVE:

We investigated the outcome of using different graft manipulation strategies among children with primary immunodeficiencies.

METHODS:

Between 2006 and 2017, 147 patients with primary immunodeficiencies received 155 mismatched grafts: 30 T-cell receptor (TCR) αβ/CD19-depleted grafts, 43 cord blood (CB) grafts (72% with no serotherapy), 17 CD34+ selection with T-cell add-back grafts, and 65 unmanipulated grafts.

RESULTS:

The estimated 8-year survival of the entire cohort was 79%, transplant-related mortality was 21.7%, and the graft failure rate was 6.7%. Posttransplantation viral reactivation, grade II to IV acute graft-versus-host disease (aGvHD), and chronic graft-versus-host disease (cGvHD) complicated 49.6%, 35%, and 15% of transplantations, respectively. Use of TCRαβ/CD19 depletion was associated with a significantly lower incidence of grade II to IV aGvHD (11.5%) and cGvHD (0%), although with a greater incidence of viral reactivation (70%) in comparison with other grafts. T-cell immune reconstitution was robust among CB transplants, although with a high incidence (56.7%) of grade II to IV aGvHD. Stable full donor engraftment was significantly greater at 80% among TCRαβ+/CD19+-depleted and CB transplants versus 40% to 60% among the other groups.

CONCLUSIONS:

Rapidly accessible CB and haploidentical grafts are suitable alternatives for patients with no HLA-matched donor. Cord transplantation without serotherapy and TCRαβ+/CD19+-depleted grafts produced comparable survival rates of around 80%, although with a high rate of aGvHD with the former and a high risk of viral reactivation with the latter that need to be addressed.

• Authors: Reem Elfeky, Ravi M Shah, Mohamed N M Unni, Giorgio Ottaviano, Kanchan Rao, Robert Chiesa, Persis Amrolia, Austen Worth, Terry Flood, Mario Abinun, Sophie Hambleton, Andrew J Cant, Kimberly Gilmour, Stuart Adams, Gul Ahsan, Dawn Barge, Andrew R Gennery, Waseem Qasim, Mary Slatter, Paul Veys
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 144 Issue 1 Pg. 280-293 (07 2019) ISSN: 1097-6825 [Electronic] United States
• PMID: 30731121 (Publication Type: Journal Article)
• Copyright: Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD19
• CD19 molecule, human
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Adolescent
• Antigens, CD19 (immunology)
• Child
• Child, Preschool
• Graft vs Host Disease (etiology, immunology)
• Humans
• Infant
• Primary Immunodeficiency Diseases (immunology, therapy)
• Receptors, Antigen, T-Cell, alpha-beta (immunology)
• Stem Cell Transplantation (adverse effects, methods)
• Virus Diseases (etiology, immunology)