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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:144

Article

Elfeky, Reem^1,2  Shah, Ravi M.^3,6  Unni, Mohamed N. M.⁴  Ottaviano, Giorgio⁵  Rao, Kanchan³  Chiesa, Robert³  Amrolia, Persis^1,3  Worth, Austen³  Flood, Terry⁴  Abinun, Mario⁴  Hambleton, Sophie⁴  Cant, Andrew J.⁴  Gilmour, Kimberly³  Adams, Stuart³  Ahsan, Gul³  Barge, Dawn⁴  Gennery, Andrew R.⁴  Qasim, Waseem¹  Slatter, Mary⁴  Veys, Paul^1,3 

[1] Univ Coll London UCL Great Ormond St Inst Child H, Mol & Cellular Immunol Unit, London, England

[2] Ain Shams Univ, Dept Paediat Allergy & Immunol, Cairo, Egypt

[3] Great Ormond St Hosp Sick Children, Blood & Bone Marrow Transplant Unit, London, England

[4] Great North Childrens Hosp, Host Def Unit, Newcastle Upon Tyne, Tyne & Wear, England

[5] Univ Milano Bicocca, Dept Paediat, Fdn MBBM, Monza, Italy

[6] Alberta Childrens Prov Gen Hosp, Dept Paediat Oncol & BMT, Calgary, AB, Canada

关键词: Mismatched stem cell transplantation;    graft-versus-host disease;    cord;    T-cell receptor alpha beta/CD19;    immune reconstitution;   

DOI  :  10.1016/j.jaci.2019.01.030

来源: Elsevier

【 摘 要 】

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) alpha beta/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 TCR alpha beta/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 TCR alpha beta(+)/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 TCR alpha beta(+)/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.

【 授权许可】

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