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Multicenter Study
. 2020 Aug 25;4(16):3900-3912.
doi: 10.1182/bloodadvances.2020001620.

Impact of donor age and kinship on clinical outcomes after T-cell-replete haploidentical transplantation with PT-Cy

Jacopo Mariotti  1 , Anna Maria Raiola  2 , Andrea Evangelista  3 , Angelo Michele Carella  4 , Massimo Martino  5 , Francesca Patriarca  6 , Antonio Risitano  7 , Stefania Bramanti  1 , Alessandro Busca  8 , Luisa Giaccone  8   9 , Lucia Brunello  8 , Emanuela Merla  4 , Lucia Savino  4 , Barbara Loteta  5 , Giuseppe Console  5 , Renato Fanin  6 , Alessandra Sperotto  6 , Luana Marano  7 , Serena Marotta  7 , Camilla Frieri  7 , Simona Sica  10 , Patrizia Chiusolo  10 , Samia Harbi  11 , Sabine Furst  11 , Armando Santoro  12 , Andrea Bacigalupo  10 , Didier Blaise  13 , Emanuele Angelucci  2 , Domenico Mavilio  14   15 , Luca Castagna  1 , Benedetto Bruno  8   9
Affiliations
Multicenter Study

Impact of donor age and kinship on clinical outcomes after T-cell-replete haploidentical transplantation with PT-Cy

Jacopo Mariotti et al. Blood Adv. .

Erratum in

Abstract

Donor selection contributes to improve clinical outcomes of T-cell-replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

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Conflict of interest statement

Conflict-of-interest disclosure: A. Santoro is on the advisory board at Bristol-Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, and Merck Sharp & Dohme; receives consultancy fees from Arqule/Sanofi; and receives speaker’s bureau fees from Takeda, Bristol-Myers Squibb, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, and Merck Sharp & Dohme. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Cumulative incidence of aGVHD and cGVHD. The 100-day cumulative incidence of grade 2 to 4 aGVHD in the whole population (A) and according to donor age (B) (≤30 years, 30-50 years, and >50 years). The 100-day cumulative incidence of grade 3 to 4 aGVHD in the whole population (C) and according to donor age (D) (≤30 years, 30-50 years, and >50 years). Two-year cumulative incidence of moderate-to-severe cGVHD in the entire population (E) and according to donor age (F) (≤30 years, 30-50 years, and >50 years).
Figure 2.
Figure 2.
Cumulative incidence of NRM and disease relapse. Three-year NRM in the whole population (A) and stratified by donor age (B) (30 years, 30-50 years, and >50 years). Three-year cumulative incidence of disease relapse in the entire population (C) and according to donor age (D) (≤30 years, 30-50 years, and >50 years).
Figure 3.
Figure 3.
Analysis of clinical outcome in terms of OS, PFS, and GRFS. Three-year OS in the whole population (A) and stratified by donor age (B). Three-year PFS in the whole population (C) and according to donor age (D). Three-year GRFS in the entire population (E) and stratified according to donor age (F) (≤30 years, 30-50 years, and >50 years).
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References

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