Haploidentical hematopoietic stem cell transplantation (haplo HSCT) has emerged as an important treatment modality. Most reports comparing haplo HSCT with post-transplant cyclophosphamide (PTCy) and other donor sources have focused on outcomes in older adults treated with reduced intensity conditioning. Therefore, in the current study, we evaluated outcomes in patients with hematological malignancy treated with myeloablative conditioning prior to haplo (n=375) or umbilical cord blood (UCB, n=333) HSCT. All haplo recipients received a 4 of 8 HLA matched graft while recipients of UCB were matched at 6-8/8 (n=145) or ≤5/8 (n=188) HLA antigens. Recipients of 6-8/8 UCB transplants were younger (14 years vs. 21 and 29 years) and more likely to have lower co-morbidity scores compared to recipients of ≤5/8 UCB and haplo HSCT (81% vs. 69% and 63%, respectively). UCB recipients were more likely to have acute lymphoblastic leukemia and transplanted in second complete remission (CR) whereas haplo HSCT recipients were more likely to have acute myeloid leukemia in first CR. Other characteristics, including cytogenetic risk were similar. Survival at 3 years was similar for the donor sources (66% haplo and 61% after ≤5/8 and 58% after 6-8/8 UCB). Notably, relapse at 3 years was lower in recipients of ≤5/8 UCB (21%, p=0.03) compared to haplo (36%) and 6-8/8 UCB (30%). However, non-relapse mortality was higher in ≤5/8 UCB (21%) compared to other groups (p<0.0001). These data suggest that haplo HSCT with PTCy after myeloablative conditioning provides an overall survival outcome comparable to that after UCB regardless HLA match group.

Introduction: Hematopoietic cell transplantation (HCT) carries significant risks for mortality, which are not proportionally shared across individuals. Among HCT recipients, we have previously shown that low socioeconomic status (SES) is predictive of increased mortality following HCT, and the underlying mechanism for this outcome is not fully explained by race, insurance status or access to care. Furthermore, following HCT, the donor immune system replaces that of the recipient, leading to long-term engraftment with donor-derived immune cells. Previous work has not addressed the influence of donor socioeconomic factors on HCT recipient outcomes. Therefore, we hypothesized that SES would impact donor hematopoietic cells and this effect would be transferrable and associated with adverse recipient outcomes. Methods: Recipients of matched unrelated donor allogeneic peripheral blood stem cell HCT between 2000-2013 for hematologic malignancy, resided in the United States (US) with a documented ZIP code, and had a HCT donor with documented US ZIP code were identified from the Center for International Blood and Marrow Transplantation Research (CIBMTR). Using donor ZIP code, SES measures of household income, poverty, education, housing and employment were derived from the U.S. Census American Community Survey. A standardized donor SES composite score was computed as an equally weighted average of the 5 standardized SES variables (mean composite score = 0, standard deviation (SD) = 1). Multivariable models, adjusted for donor and recipient characteristics, were used to evaluate associations between donor SES composite score with HCT recipient disease free survival (DFS), overall survival (OS), treatment related mortality (TRM), relapse, and acute and chronic graft versus host disease (GVHD). Results were considered significant if P < 0.01. Results: Among 2,005 HCT recipients, median age at diagnosis was 51 years (range 1-77), 44% were female, and 55% had acute myeloid leukemia. Median post-HCT follow up was 120 months (range 4-219). Donors were 44% female and median age at hematopoietic cell donation was 34.7 years (range 18-62). The standardized donor composite scores ranged from -2.6 to 3.9, with a higher composite score indicative of greater socioeconomic disadvantage. Multivariable analyses identified significant associations between the standardized donor SES composite score and DFS (HR 1.07 per SD SES, 95% CI 1.02-1.13; p=0.0088), OS (HR 1.09 per SD SES, 95% CI 1.04-1.15; p=0.0007), and TRM (HR 1.10 per SD SES, 95% CI 1.03-1.17; p=0.0049). Significant associations were not identified between donor SES and relapse or GVHD. Quantitatively, recipients transplanted with cells from a donor of greater socioeconomic disadvantage (i.e. SES composite score 2 SD above the mean) experienced a 10% reduction in DFS and OS, and a 5% increase in TRM at 3 years compared with those transplanted with cells from a high-SES donor (SES composite score 2 SD below the mean) (Figure). Conclusions: For the first time, we have demonstrated that socioeconomic disadvantage among HCT donors results in adverse transplant outcomes in the HCT recipient. This novel finding suggests that SES has biologic impacts down to the stem cell level that persist even when transplanted into a new host during HCT. The implications of these findings are broad and suggest the need for public health interventions targeting socioeconomic support as a means for preventing social disparities in cancer treatment outcomes. Figure 1 Figure 1. Disclosures Verneris: Novartis: Other: advisory board; jazz: Other: advisory board; Fate Therapeutics: Consultancy.

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Summary It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post‐transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013–2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non‐relapse mortality (NRM). The analysis demonstrated a significant, non‐linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25–30 [hazard ratio (HR) 1.66–1.71, p < 0.05] and MUD transplants at a BMI of 25–45 (HR, 1.61–3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.

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6500 Background: Allogeneic hematopoietic cell transplantation (HCT) carries significant risks, with low socioeconomic status (SES) being predictive of increased mortality. Our team recently discovered that socioeconomic disadvantage among unrelated HCT donors results in decreased recipient overall survival (OS) and increased treatment-related mortality (TRM) within a cohort from the Center for International Blood and Marrow Transplant Research (CIBMTR). We also demonstrated that upregulation of the stress- and SES-related gene expression profile termed the ‘conserved transcriptional response to adversity’ (CTRA) is associated with low SES and worse outcomes among HCT recipients. Here, we hypothesize that donor immunologic characteristics associated with neighborhood socioeconomic disadvantage (CTRA) will confer prognostic risk to HCT recipients as indicated by inferior long-term recipient outcomes. Methods: Among a subset of the above cohort for which donor whole blood samples were available from the CIBMTR repository, we evaluated whether donor cell CTRA gene regulation was associated with inferior HCT outcomes at 3 years in recipients being treated for hematologic malignancy. Multivariable models adjusted for donor and recipient characteristics evaluated associations between donor CTRA and recipient OS, TRM, disease free survival (DFS), relapse, and acute and chronic graft versus host disease. Results were considered significant if P<0.05. Results: We identified 263 donor-recipient pairs for study inclusion. Median recipient age at hematologic malignancy diagnosis was 53 years (range 19-77), 46% were female, and 54% had acute myeloid leukemia. Donors were 35% female and median age at donation was 31 years (range 18-60). In RNA sequencing data from HCT donors, greater CTRA expression was associated with reduced OS (covariate-adjusted HR=1.94/CTRA SD, 95% CI [1.01, 3.71], p=.046) which was driven predominately by increased TRM (adjusted HR=5.04, [2.20, 11.50], p=.0001). These clinical outcomes are consistent with those observed to be associated with donor SES in our prior work. Donor cell effects on transplant outcomes derived predominately from the pro-inflammatory component of the CTRA (OS: adjusted HR=1.67, [1.20, 2.33], p = .0026; TRM: adjusted HR=2.21, [1.21, 4.06], p=.010) and emerged above and beyond the effects of the recipients’ own SES, as well as multiple other recipient disease, treatment, and demographic factors. Donor CTRA was not associated with relapse, DFS, or other transplant outcomes. Conclusions: For the first time, we show that transcriptome patterning among HCT donors, consistent with neighborhood SES disadvantage, results in adverse recipient HCT outcomes. These findings suggest that SES has a biologic impact at either the stem or immune cell level that persists even when transplanted into a new host.

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