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

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.

Impact of allogeneic stem cell transplantation comorbidity indexes after haplotransplant using post‐transplant cyclophosphamide

“…Indeed, Elsawy et al 16 reported no statistically significant differences in terms of OS nor NRM for patients with high AC/AI in a cohort of 117 patients receiving Haplo-SCT (respectively HR: 1,19, p = 0.60 and HR: 1.66, p = 0.08 for AC/AI ≥4 vs. 0-3). The discrepancy with other reports showing an impact of HCT-CI [6][7][8][9] may likely be due to the retrospective nature and potential selection biases for all of these studies including ours. However, our cohort is currently the largest one having evaluated the impact of C/AI and AC/AI in Haplo-SCT.…”

“…Similar conflicting data have been observed after Haplo-SCT with PTCY. 8 In conclusion, it seems that the HCT-CI, C/AI, and AC/ AI scores do not predict survivals nor NRM in Haplo-SCT with PTCY, suggesting that pre-transplant comorbidities should not be a contra-indication to this procedure. As donor age is the only factor predicting survivals and NRM in this series, the selection of a younger donor should be the preferred choice whenever possible for these patients.…”

“…Interestingly, the HCT-CI was found to influence NRM without impacting survivals 7 or conversely influence survivals without impacting NRM. 8 It has also been identified to predict graft-versus-host disease (GVHD) 13 or relapse. 15 Conversely, the performance of C/AI and AC/AI scores has been poorly evaluated after Haplo-SCT.…”

“…Haploidentical Allo‐HSCT (Haplo‐SCT) using post‐transplant cyclophosphamide (PTCY) is a procedure in constant expansion worldwide. 5 The HCT‐CI has been already explored in this setting yet with conflicting results as it has been shown to impact 6 , 7 , 8 , 9 or not 10 , 11 , 12 , 13 , 14 survivals and/or NRM. Interestingly, the HCT‐CI was found to influence NRM without impacting survivals 7 or conversely influence survivals without impacting NRM.…”

Stem-Cell Transplantation in Adult Patients with Relapsed/Refractory Hodgkin Lymphoma

“…As the best strategy for choosing a haploidentical donor is selecting a younger haploidentical donor, a sibling is preferable to a parent donor, and a father donor is better than a mother in terms of improving outcomes [67].…”