Analysis of 3,843 Unrelated Donors (URD) for 455 Allograft Candidates Reveals Low URD Availability with Marked Racial/ Ethnic Disparities: Major Implications for Transplant Center & Registry Operations

Introduction: Although hematologic malignancies patients (pts) often require urgent transplants, the degree to which unrelated donor (URD) availability is a barrier to prompt allografting is not established.

Methods: We evaluated availability of requested URDs 1/2020-12/2022, overall & by pt ancestry, in 455 consecutive adults with acute leukemia, MDS or MPN who had a formal URD search & for whom ≥ 1 URDs were pursued for confirmatory typing (CT). We also examined donor location & Donor Readiness Score (DRS; the prediction of a donor's likelihood of availability for CT) by pt ancestry. We hypothesized that URD availability is a major barrier to transplant for underserved racial/ ethnic groups & this has not improved in the post-pandemic era.

Results: Of 455 pts [median age 63 yrs, range 21-81; 250/455 (55%) with acute leukemia], 74% (335/455) had European (EURO) & 26% (120/455) non-European (non-EURO) ancestry. For these 455 pts, 3,843 URDs (median age 27 yrs, range 17-61; 1,951/3,843 [51%] male) were requested for CT or simultaneous CT-workup; 71% (2,730/3,843) of URDs were for EURO & 29% (1,113/3,843) for non-EURO pts; & 56% (2,140/3,843) were from domestic & 44% (1,703/3,843) international registries. Of 2,775 URDs with an assigned DRS, the median score was 63% (range 16-94%). URDs requested for non-EURO pts were more likely to be domestic [EUROs: 1,411/2,730 (52%) vs non-EUROs: 729/1,113 (65%), p < .001]. Also, URDs for non-EUROs had markedly lower median DRS (EUROs: 71% vs non-EUROs: 52%) with over 15x the proportion with DRS ≤ 30% [EUROs: 30/2,073 (1.5%) vs non-EUROs: 160/702 (23%), p < .001].

Table 1A-C outlines URD availability at CT & workup, overall & by pt ancestry. In summary:

• At CT, per pt: More non-EURO pts had greater than 10 URDs requested (p = .045), less than 5 URDs that agreed to CT (p < .001), & at least 5 URDs unavailable (p < .001), compared with EUROs.

• At workup, per pt: For over one-quarter (134/455, 29%), 3-5 URDs were requested. More non-EURO pts had less than 2 URDs that agreed to workup (p = .007) & at least 2 URDs unavailable (p = .017), compared with EUROs.

• At CT: Only half (2,036/3,843, 53%) of requested URDs were available for CT or CT-workup. URDs were less likely to agree to CT if requested for non-EURO pts ( vs EUROs), if domestic ( vs international), or if lower DRS (p < .001 for each).

• At workup: Of URDs requested for workup after CT, while 461/598 (77%) agreed, URDs requested for non-EURO pts were less likely to agree (p < .001).

• Overall: Availability of the 3,843 URDs requested for the 455 pts was low, with less than half available (Fig. 1A). Notably, URDs requested for non-EURO pts had lower availability (p < .001).

• By ancestry sub-type: African & non-Black Hispanic pts had the lowest URD availability.

• Over time: When examining 2020-2022, the worse URD availability for non-EURO pts is not improving in the post-pandemic era (Fig. 1B).

• URD provision: Of pts with ≥ 1 URD who agreed to workup, 12% did not have an URD available within 14 days of the 1st proposed collection date, & of 263 5-8/8 URD recipients for whom a primary URD was selected, over one third (103/263, 39%) were not transplanted with that donor. Of transplanted pts, as expected, non-EURO pts were less likely to receive 8/8 URDs (p < .001) &, for those who did, their URDs were older (p = .018), & 5-7/8 URDs requested for non-EUROs were more HLA-mismatched (p < .001).

Conclusions: We demonstrate significant ongoing disparities in URD access that have major implications for transplant center & registry operations. Incorporating careful assessment of pt ancestry, transplant centers should pursue, & registries should permit, simultaneous pursuit of multiple URDs, especially for non-EURO pts, deciding at the outset what degree of HLA-mismatch will be accepted if an URD is desired but an 8/8 URD is unlikely (Davis et al, TCT 2023). Moreover, centers are ethically obliged to inform pts if timely URD procurement is unlikely, especially as these pts are commonly from underserved racial/ ethnic groups. Registries need to address high URD attrition, & prospective investigation of efforts to speed donor identification are needed. Finally, utilization of all alternative donors (5-7/8 URD, haploidentical & cord blood) is needed to facilitate donors for all in the time required for optimized transplantation.