Analysis of disparities in time to allogeneic transplantation in adults with acute myelogenous leukemia

Abstract

While alternative donors extend transplant access, whether recipient ancestry impacts the time to allogeneic transplant is not established. We analyzed the likelihood of clinically significant delays to allograft by patient ancestry in 313 transplanted adult acute myelogenous leukemia (AML) patients. Non-European ancestry patients (n = 99) were more likely than Europeans (n = 214) to receive HLA-mismatched donor allografts (45% versus 24%, p < 0.001). Overall, the median time from transplant indication to allograft was 127 days (range 57-1,683). In multivariable analysis, non-Europeans had an increased risk of prolonged indication-transplant time > 180 days (OR 2.1, 95%CI:1.4-5.6, p = 0.012) due to significant delays in indication-consult > 90 days (OR 2.8, 95%CI:1.3-4.5, p = 0.005) and consult-transplant > 120 days (OR 2.4, 95%CI:1.2-3.7, p = 0.005). Compared to recipients of HLA-matched unrelated donors (URD), HLA-mismatched adult donor recipients were at increased risk of delayed indication-transplant whereas matched sibling and cord blood recipients were at lower risk. Sub-analysis showed more indication-transplant delays in non-European versus European 8/8 URD recipients (44% versus 19% > 180 days, p = 0.004). Finally, the pandemic further exacerbated delays for non-Europeans. In summary, while non-European AML patients are less likely to receive 8/8 URDs as expected, if they do their transplants are delayed. HLA-identical siblings and cord blood facilitate the fastest transplants regardless of patient ancestry whereas other adult donor transplants are delayed. Strategies to mitigate referral barriers, hasten donor evaluation, and utilize all alternative donor sources are critical to ensure timely transplantation for AML patients.

A new beginning: can omidubicel emerge as the next, viable alternative donor source?

“… 27 In an observational study at Memorial-Sloan Kettering, racial disparities persisted despite the advancements in alternative donor allogeneic hematopoietic cell transplantation (HCT), using mismatched URD, haploidentical, and UCB grafts. 28 In this real-world report conducted during 2016–2021, access to 8/8 URD had increased over time for Europeans versus non-Europeans, up to 95% versus 61% ( p < 0.001) respectively. Thus, UCB use has proven successful in patients with high-risk malignancies who lack matched or single antigen mismatched URD options.…”

“…an observational study at Memorial-Sloan Kettering, racial disparities persisted despite the advancements in alternative donor allogeneic hematopoietic cell transplantation (HCT), using mismatched URD, haploidentical, and UCB grafts. 28 30 The study objectives and eligibility criteria were similar between trials, and showed similar outcomes including 1-year overall survival (OS), time to neutrophil engraftment, and the rates of GVHD. The 1-year probabilities of OS and progression-free survival (PFS) were 54% and 46% respectively for dCBT, and 62% and 48% respectively for haplo-BM transplantations.…”

Inaccuracies in assignment of patient race and ethnicity: implications for unrelated donor searches and health care delivery

“…Accurate patient ancestry determination is critical in the evaluation of candidates for allogeneic bone marrow transplantation (BMT) without suitable related donors, given that patients with non-European ancestry are much less likely to have an 8 of 8 HLA–matched unrelated donor (URD) 1 , 2 , 3 , 4 and are more likely to suffer delays to transplant 5 which can adversely affect transplant outcomes. 6 , 7 It is known that recording patients with full or part non-European origins as White non-Hispanic can result in inaccurate and potentially dangerous overestimation of the likelihood of securing an 8 of 8 URD, thereby delaying pursuit of alternative–mismatched adult donors or cord blood grafts.…”

Association between non-European ancestry, low socioeconomic status, and receipt of HLA-disparate allografts in adult BMT recipients

“…Although ancestry 1 , 2 , 3 , 4 and socioeconomic status 5 , 6 , 7 (SES) both affect allogeneic transplant care delivery, the association between these variables and their interaction with stem cell donor type are not established. Given that patients from historically marginalized groups are more likely to have lower SES 8 and face financial hardship compared with other patients, 9 , 10 and because non-European ancestry patients are more likely to lack an 8/8 human leukocyte antigen (HLA)-matched unrelated donor (URD) compared with their European counterparts, 1 , 4 we hypothesized that low SES disproportionately affects non-European recipients of HLA-disparate grafts (cord blood [CB], haploidentical, or 4/8 to 7/8 mismatched URD [mmURD] grafts).…”

“…During the study period, in the absence of an HLA-identical sibling donor, an 8/8 HLA allele-matched URD was prioritized followed by either double unit CB or haploidentical grafts as previously described. 2 mmURDs have been used as an additional alternative more recently. Ancestry was classified as previously described 11 based on detailed kinship history performed by the transplant staff during the pretransplantation evaluation.…”