Impact of Donor Age and Relationship on Outcomes of Peripheral Blood Haploidentical Hematopoietic Cell Transplantation
Authors: Pruitt Aaron , Gao Feng , De Togni Elisa , Singareddy Aaron , Cochran Hunter , Godbole Sonia , Slade Michael , Abboud Ramzi 
Published: November 2021

Abstract
Introduction: Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly utilized therapy for a variety of hematologic malignancies. Determining which donor characteristics affect transplant outcomes is of particular interest in haplo-HCT, as there are often multiple donors available for a given patient. A survival benefit with younger donors has been reported in some recent observational studies (DeZern et. al., Blood Advances, March 2021); (Canaani et. al., AJH, Sep. 2017). A decrease in non-relapse mortality (NRM) and increase in relapse with no overall survival difference associated with younger donors has also been observed (Mariotti et. al., Blood Advances, June 2020). These previous studies have utilized populations with bone marrow as the predominant stem cell source. Solomon et al. (BBMT Sep. 2018) observed poorer survival, increased relapse, and worse NRM with parent donors relative to children in a largely peripheral blood population. HLA DR and DP mismatch were noted to be associated with improved survival. Here we describe outcomes in peripheral blood haplo-HCT and their association with potentially selectable donor characteristics including age and relationship to the patient.
Patients and Methods: We performed a retrospective review of patients who underwent peripheral blood haplo-HCT with PtCy from July 2009 through May 2021. A total of 323 patients were identified with AML (205), ALL (43), MDS (26), and other (49). Univariate and multivariate analyses (MVA) were conducted examining the effect of donor characteristics on overall survival (OS), NRM, relapse, acute and chronic GVHD. Donor characteristics included age, relationship, ABO status, CMV status, and HLA match grade. We controlled for patient characteristics known to affect outcomes including disease type, DRI, HCT CI, KPS, active disease at transplant, myeloablative conditioning, and prior HCT.
Results: Median donor age was 40 (range 15-71) with male predominance (64%). Most were ABO compatible (63%) - 12% had major ABO mismatch, 20% minor, and 4% bidirectional. Donor-recipient CMV status matched in 61% of pairs, 13% were donor positive-recipient negative, 26% donor negative-recipient positive. Most were 5/10 HLA matched (51%) with 20% 6/10 and 13% 7-9/10. Univariate analysis revealed that increasing donor age was associated with higher NRM (HR 2.29, p=0.005 for donors age 30-44; HR 2.06, p=0.012 age &gt; 44) but lower relapse risk (HR 0.56, p=0.012 age 30-44; HR 0.69, p=0.10 age &gt; 44). There were no differences in aGVHD or cGVHD based on donor characteristics in univariate analysis. In MVA, relapse risk was lower in patients with older donors , p=0.046). In contrast, NRM was higher in patients with older donors (HR 1.73 age 30-44, HR 1.69 age &gt; 44, p=0.010). There was no difference in overall survival based on donor age (HR 1.23 age 30-44, HR 1.38 age &gt; 44, p=0.11). We next examined the effect of donor relationship on outcomes while controlling for donor age, patient age, and patient disease risk factors. We found no difference in outcomes between parent, sibling, or child donors.
Conclusions: Increasing donor age was associated with lower relapse risk but higher NRM. These competing effects resulted in no difference in OS based on donor age. Other donor factors including relationship (parent / sibling / child), CMV status, ABO mismatch, donor sex, and HLA match grade were not associated with outcomes. Solomon et al. reported better outcomes with child compared to parent donors, a finding not replicated here, however our analysis controlled for donor age which could have been a proxy for relationship in their study. These data suggest that in peripheral blood haplo-HCT, younger donors may be preferred in patients with high risk of transplant related complications. In contrast, older donors may be preferred in patients where relapse risk is high. Data on HLA-DR and DP match is being analyzed and will be presented at the ASH 2021 meeting.
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Disclosures
No relevant conflicts of interest to declare.