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. 2022 Feb 22;6(4):1319-1328.
doi: 10.1182/bloodadvances.2020004072.

T-replete HLA-matched grafts vs T-depleted HLA-mismatched grafts in inborn errors of immunity

Su Han Lum  1   2 , Sinéad Greener  1 , Inigo Perez-Heras  1 , Daniel Drozdov  1 , Rebecca P Payne  2 , Helen Watson  3 , Kay Carruthers  4 , Robert January  1 , Zohreh Nademi  1   2 , Stephen Owens  1 , Eleri Williams  1 , Sheila Waugh  5 , Shirelle Burton-Fanning  5 , Timmothy Ronan Leahy  6 , Andrew Cant  1   2 , Mario Abinun  2 , Terry Flood  1 , Sophie Hambleton  1   2 , Andrew R Gennery  1   2 , Mary Slatter  1   2
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T-replete HLA-matched grafts vs T-depleted HLA-mismatched grafts in inborn errors of immunity

Su Han Lum et al. Blood Adv. .

Abstract

Hematopoietic cell transplantation (HCT) has become standard-of-care for an increasing number of inborn errors of immunity (IEI). This report is the first to compare transplant outcomes according to T-cell-replete (ie, T-replete) HLA-matched grafts using alemtuzumab (n = 117) and T-cell-depleted (ie, T-depleted) HLA-mismatched grafts using T-cell receptor-αβ (TCRαβ)/CD19 depletion (n = 47) in children with IEI who underwent first HCT between 2014 and 2019. All patients received treosulfan-based conditioning except patients with DNA repair disorders. For T-replete grafts, the stem cell source was marrow in 25 (21%) patients, peripheral blood stem cell (PBSC) in 85 (73%), and cord blood in 7 (6%). TCRαβ/CD19 depletion was performed on PBSCs from 45 haploidentical parental donors and 2 mismatched unrelated donors. The 3-year overall survival (OS) and event-free survival for the entire cohort were 85% (77%-90%) and 79% (69%-86%), respectively. Analysis according to age at transplant revealed a comparable 3-year OS between T-replete grafts (88%; 76%-94%) and T-depleted grafts (87%; 64%-96%) in younger patients (aged <5 years at HCT). For older patients (aged >5 years), the OS was significantly lower in T-depleted grafts (55%; 23%-78%) compared with T-replete grafts (87%; 68%-95%) (P = .03). Grade III to IV acute graft-versus-host disease was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete cord blood, and 2% of T-depleted PBSC (P = .73). Higher incidence of viremia (P < .001) and delayed CD3 reconstitution (P = .003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCRαβ/CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Graft composition and engraftment kinetics according to T-replete marrow, T-replete PBSC, T-replete CB, and T-depleted PBSC. (A) Total nucleated cell (TNC) dose, ×108/kg. (B) CD34+ cells, ×106/kg. (C) CD3+ cells, ×108/kg. (D) CD19+ cells, ×107/kg. (E) Neutrophil recovery. (F) Platelet recovery. NS, not significant.
Figure 2.
Figure 2.
Cumulative incidence of aGvHD and survival according to T-replete and T-depleted grafts. (A) Grade II to IV aGvHD. (B) Grade III to IV aGvHD. (C) OS according to age at transplant. (D) EFS according to age at transplant.
Figure 3.
Figure 3.
Cumulative incidence of viremia (CMV, adenovirus [AdV], EBV and HHV6) according to T-replete and T-depleted grafts.
Figure 4.
Figure 4.
A matched-pair analysis for immune reconstitution kinetics posttransplant. Means (± standard error of the mean) CD3+ (A), CD4+ (B), CD8+ (C), activated T lymphocytes (D), natural killer (NK) cells (E), and CD19+ lymphocytes (F) measured at different time points posttransplant. *P < .05; **P < .001.
Figure 5.
Figure 5.
The latest donor chimerism in T-replete and T-depleted grafts. (A) Myeloid donor chimerism. (B) T-lymphocyte chimerism.
See this image and copyright information in PMC

References

    1. Tangye SG, Al-Herz W, Bousfiha A, et al. . Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee [published correction appears in J Clin Immunol. 2020;40(1):65]. J Clin Immunol. 2020;40(1):24-64. - PMC - PubMed
    1. Cole T, McKendrick F, Titman P, et al. . Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant. J Clin Immunol. 2013;33(1):8-13. - PubMed
    1. Lum SH, Flood T, Hambleton S, et al. . Two decades of excellent transplant survival for chronic granulomatous disease: a supraregional immunology transplant center report. Blood. 2019;133(23):2546-2549. - PubMed
    1. Gragert L, Eapen M, Williams E, et al. . HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339-348. - PMC - PubMed
    1. Slatter M., Rao K, Amrolia P, et al. . Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117(16):4367-4375. - PubMed

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