Disparities In Transplant Outcomes Research Articles

Post-Transplant Cyclophosphamide Equalizes Clinical Outcomes of Allogeneic Hematopoietic Cell Transplantation across Racial and Ethnic Populations

Background Despite being the only curative option for many hematologic malignancies, allogeneic hematopoietic cell transplant (HCT) has been plagued by health disparities due to differences in access, donor availability, and outcomes across racial and ethnic minority populations (REM) (Gragert, NEJM, 2014). Even when a matched donor is available, HCT outcomes for REM patients are historically worse compared to non-Hispanic white (NHW) patients. (Landry, Stem Cell Investigation, 2021). The development of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has led to increased use of HLA haploidentical (haplo) or mismatched unrelated donors (MMUD) with comparable outcomes to HLA matched HCT (McCurdy, Advances in Hematology, 2015). While PTCy allows for almost every transplant-eligible REM patient to have a suitable donor, there is limited data evaluating whether this transplant platform results in similar outcomes for REM patients compared to NHW patients. The aim of this study was to investigate if disparities in transplant outcomes still exist between REM patients and NHW patients who received an HLA mismatched transplant with PTCy. Methods We retrospectively analyzed 302 consecutive adult patients who underwent haplo or MMUD HCT with PTCy at Moffitt Cancer Center between 2014 and 2022. All endpoints were compared between four groups: NHW, Hispanic-White, Black, and Other (Asian, biracial, or multiracial.) Results In this cohort, 59% (n=178) of patients identified as NHW, 14% (n=41) as Hispanic-White, 16% (n=48) as Black, 7% (n=21) as biracial or multiracial, and 4% (n=11) identified as Asian. Most patients were male (57%). The median age of all patents was 58. The most common indication for transplant was acute myeloid leukemia (48%), myeloablative conditioning (MAC) was utilized in 42%, and 89% received peripheral blood stem cells grafts. REM patients were more likely to be <65 years of age (60% vs 66-90%, p<0.001), female (36% vs 50-54%, p=0.04), and receive MAC conditioning (33% vs 40-71%, p<0.001). Median follow-up was 21 months. In all clinical outcomes, no significant differences were observed between NHW and REM patients. At day 100, the cumulative incidence of Grade II-IV aGVHD was 37% [95% CI 30-44%] for NHW patients, 32% [95% CI, 18-46%] for Hispanic-White patients, 27% [95% CI, 15-40%] for Black patients, and 26% [95% CI, 13-41%] for patients of Other races (p= 0.38). The cumulative incidence of moderate to severe cGVHD at 2 years was 21% [95% CI 15-28%] for NHW patients, 25% [95% CI, 13-39%] for Hispanic-White, 17% [95% CI, 7.8-29%] for Black, and 27% [95% CI, 13-42%] for patients of Other races (p = 0.80). At 2 years, the probability of relapse was 25% [95% CI 19-32%] for NHW patients, 24% [95% CI, 12-39%] for Hispanic-White patients, 27% [95% CI, 15-40%] for Black patients, and 18% [95% CI, 7.1-33%] for patients of Other races (p = 0.97). During the same time interval, non-relapse mortality (NRM) for NHW patients, Hispanic-White patients, Black patients, and patients of Other races were 19% [95% CI, 13-25%], 15% [95% CI, 5.9-27%], 19% [95% CI, 9.4-32%], and 24% [95% CI, 11-40%] (p = 0.73), respectively. At 2 years, relapse free survival (RFS) was 56% [95% CI 49-64%] for NHW patients, 61% [95% CI, 47-79%] for Hispanic-White patients, 54% [95% CI, 41-71%] for Black patients, and 58% [95% CI, 43-78%] for patients of Other races (p = 0.77). Comparably, OS at 2 years for NHW, Hispanic-White patients, Black patients, and patients of Other races was 64% [95% CI, 57-72%], 72% [95% CI, 60-88%], 53% [95% CI, 40-71%], and 63% [95% CI, 49-83%] respectively after two years (p = 0.92). In multivariate analysis, race/ethnicity had no significant impact on incidence of Grade II-IV aGVHD (p= 0.40), moderate/severe cGVHD (p = 0.80), rates of relapse (p = 0.86), NRM (p= 0.77), RFS (p = 0.69), or OS (p = 0.64) (Table). Conclusions These results show that the use of HLA mismatched donor HCT with PTCy achieves comparable clinical outcomes between REM and NHW patients. Our study suggests that PTCy effectively contributes to equitable healthcare in the setting of allogeneic HCT for REM patients.

Education and Psychosocial Factors Predict Odds of Death After Transfer to Adult health Care in Pediatric Liver Transplant Patients.

To analyze demographic, psychosocial, and clinical factors in pediatric liver transplant recipients for their association with death or loss to follow up in adulthood. We aimed to better understand known health disparities in transplant outcomes and identify potentially modifiable risk factors prior to transfer. A retrospective cohort study of children who underwent liver transplantation at a large tertiary transplant center and were transferred to adult care between 2000 and 2015. During the study period, 101 qualifying patients were transferred. Ninety-three individuals followed with an adult provider, while 8 were lost to follow up. In total 23 of 93 patients died after transfer (24.7%). Several childhood factors were associated with adult death: Black race [odds ratio (OR) 6.59, P < 0.001]; psychiatric illness or substance use (OR 2.81, P = 0.04); failure to graduate high school before transfer (OR 9.59, P < 0.001); posttransplant tacrolimus medication-level variability index >2.5 (OR 5.36, P = 0.04); provider documentation of medication nonadherence (OR 4.72, P = 0.02); acute cellular rejection (OR 4.44, P = 0.03); the presence of diabetes mellitus (OR 5.71, P = 0.001), and chronic kidney disease (OR 2.82, P = 0.04). Failure to graduate HS was associated with loss to follow up ( P < 0.001). On multivariate analysis, Black race, substance use, diabetes, and failure to graduate HS retained association with adult death (each P < 0.05). Complex, intertwined patient characteristics are associated with increased odds of death in pediatric liver transplant recipients transferred to adult care. Early recognition of high-risk patients and intervention for modifiable factors, such as improved HS graduation and substance use prevention, may improve long-term outcomes.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation

BackgroundAfrican American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics.MethodsOutcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients.ResultsTransplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010.ConclusionRelative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Improving Trends in 6-month Mortality after Heart Transplant in White vs. Black Recipients

<h3>Purpose</h3> We previously reported improving 30-year trends in short-term heart transplant outcomes using Scientific Registry of Transplant Recipients (SRTR). While racial disparities in transplant outcomes are well-documented, how these improving trends differ by racial subgroups has not been studied. <h3>Methods</h3> Using SRTR, we identified all adult heart recipients with racial subgroups white or black. Temporal changes in recipients, donors, and providers were described. Outcome of all-cause death 6 months post-transplant was analyzed by race. Multivariable modified Poisson regression estimated yearly risk of mortality compared to 1989 adjusted for population characteristics and tested for race-year interaction. <h3>Results</h3> Among 58,204 heart recipients, frequency of black recipients increased 8.6%-23.9% from 1989-2017. Known risk factors (<i>e.g.</i> age ≥ 55, IABP) were more frequent in white and increased over 30 years in both groups. More black recipients had initial urgency of Status 1a/b. In black recipients, 9.5% experienced all-cause death within 6 months of transplant compared to 10.2% of white. Adjusting for population characteristics, mortality risk in black recipients was 13% higher relative to white recipients (p<0.05); yet we observed similar improving trends in 6-month mortality over time in black and white recipients (p=0.98). <h3>Conclusion</h3> From 1989 to 2017, an increasing proportion of heart recipients are black, a racial subgroup that continues to be associated with heightened mortality risk within 6 months post-transplant. Nevertheless, 30-year trends in short-term outcomes have been improving irrespective of recipient race.

Variation in Racial Disparities in Liver Transplant Outcomes Across Transplant Centers in the United States.

Little is known about the role that transplant centers may play in perpetuating racial disparities after liver transplantation, which are unexplained by patient-level factors. We examined variation in between-center and within-center disparities among 34,114 Black and White liver transplant recipients in the United States from 2010 to 2017 using Scientific Registry of Transplant Recipient (SRTR) data. We used Cox proportional hazards models to calculate transplant center-specific Black-White hazard ratios and hierarchical survival analysis to examine potential effect modification of the race-survival association by transplant center characteristics, including transplant volume, proportion of Black patients, SRTR quality rating, and region. Models were sequentially adjusted for clinical, socioeconomic, and center characteristics. After adjustment, Black patients experienced 1.11 excess deaths after liver transplant per 100 person-years compared with White patients (95% confidence interval [CI], 0.65-1.56), corresponding to a 21% increased mortality risk (95% CI, 1.12-1.31). Although there was substantial variation in this disparity across transplant centers, there was no evidence of effect modification by transplant center volume, proportion of minority patients seen, quality rating, or region. We found significant racial disparities in survival after transplant, with substantial variation in this disparity across transplant centers that was not explained by selected center characteristics. This is the first study to directly evaluate the role transplant centers play in racial disparities in transplant outcomes. Further assessment of the qualitative factors that may drive disparities, such as selection processes and follow-up care, is needed to create effective center-level interventions to address health inequity.

Different Subsets of Haematopoietic Cells and Immune Cells in Bone Marrow between Young and Old Donors

Background Young donors are reported to be associated with better transplant outcomes than old donors in allo-HSCT, but the underlying mechanism is still uncertain. Successful allo-HSCT relies on the rapid reconstitution of donor-derived haematopoietic and immune systems in the recipient. Therefore, characterizing the differences in percentages of HSCs and progenitors and immune cell subtypes between young and old donors may help explain the disparities in transplant outcomes. In humans, HSCs give rise to multipotent progenitors (MPPs) that further segregate into either common myeloid progenitors (CMPs) or multipotent lymphoid progenitors (MLPs), which in turn segregate into either common lymphoid progenitors (CLPs) or granulocyte-macrophage progenitors (GMPs). CMPs further segregate into either megakaryocyte-erythroid progenitor (MEPs), or GMPs. However, differences in the frequencies of HSCs and their progenitors between young and old adults remain uncertain. In addition, aGVHD is generally considered to be associated with increased ratios of donor Th1/Th2, Tc1/Tc2 and M1/M2 macrophage. However, little is known about the cytokine-producing T cell subsets and macrophage subsets in BM between young and old donors. Aims To evaluate the different subsets of HSCs and their progenitors and immune cells among young (aged &amp;lt;30 years), middle-aged (aged 30-45 years), and old donors (aged &amp;gt;45 years). Moreover, to analyze the association between donor characteristics and HSC frequency. M ethods In this prospective study, a total of 60 healthy adult donors, including 20 young donors, 20 middle-aged donors, and 20 old donors were enrolled. The frequencies and ROS levels of BM HSCs(CD34+CD38−CD90+CD45RA−) and progenitors including MPPs(CD34+CD38−CD90−CD45RA−), MLPs(CD34+CD38−CD45RA+), CLPs(CD34+CD38+CD7−CD10+CD45RA+), GMPs(CD34+CD38+CD7−CD10−CD45RA+), CMPs(CD34+CD38+CD7−CD10−CD135+CD45RA+), and MEPs(CD34+CD38+CD7−CD10−CD135−CD45RA−) were quantified by flow cytometry. Furthermore, T cell and macrophage subsets were analyzed in young, middle-aged and old donors by flow cytometry. Effector T cells, naïve T cells, effector memory T cells and central memory T cells were identified as CD45RA+CCR7−, CD45RA+CCR7+, CD45RA−CCR7−, and CD45RA−CCR7+. Th1, Th2, Tc1 and Tc2 were identified as CD3+CD8−IFN-γ+, CD3+CD8−IL-4+, CD3+CD8+IFN-γ+ and CD3+CD8+IL-4+, respectively. In addition, M1 and M2 were identified as CD14+CCR2+CD68+ and CD14+CX3CR1+CD163+. Moreover, the association of donor characteristics with HSC frequency was analysed by univariate and multivariate analysis. Results To determine the differences in HSCs and progenitors in different age donors, HSCs and six subpopulations were compared among young, middle-aged and old donors. The frequencies of HSCs and myeloid progenitors, including CMPs and MEPs in CD34+ cells were significantly lower and the frequencies of lymphoid progenitors including MLPs and CLPs in CD34+ cells were higher in the BM of young donors than in that of old donors. Significantly lower levels of ROS in HSCs and progenitors were observed in young donors than in the other donors. Furthermore, to investigate the differences in the differentiation potential from HSCs to immune cells in different age donors, T cell and macrophage subsets were compared among the three donor age groups. Young donors demonstrated a lower CD4+/CD8+ T cell ratio, lower memory T cell frequency and higher naïve T cell frequency in both CD4+ cells and CD8+ cells. Importantly, BM immune cells from young donors polarized towards less pro-inflammatory T cells characterized by Th1 and Tc1, and more immune suppressor cells, such as M2, than those from old donors. As a result, young donors had lower ratios of Th1/Th2, Tc1/Tc2 and M1/M2 in BM. In addition, multivariate analysis showed that age≥37 was independently correlated with a higher HSC frequency. Conclusion BM HSCs from young donors exhibited a lower frequency, balanced myeloid-lymphoid differentiation potential, lower ROS level and produced more immune suppressors and fewer immune effector cells than those from old donors. Donor age might be a good predictor of HSC frequency. Although further validation is required, the differences in the frequency and immune differentiation potential of HSCs in BM between young and old donors may partly explain the different outcomes of allo-HSCT. Disclosures No relevant conflicts of interest to declare.

Outcomes of Heart Transplantation in Adults with Congenital Heart Disease Since UNOS Allocation System Change: UNOS Registry Analysis

Outcomes in cardiac transplantation (HT) in patients with congenital heart disease (CHD) with the UNOS registry are well defined. The UNOS allocation system prioritized patients with CHD and created greater clarity regarding upgrading listing urgency based on exception status for this group. We sought to examine the wait list times and post-HT outcomes in this population since the implementation of the new allocation system and compare them to outcomes prior to this change. Patients with CHD who had undergone HT 6 months prior to the change in UNOS allocation system (N=144) and patients with CHD who had undergone HT in the 6 months since the implementation of the new system (N=61) were identified. Variables including age, sex, diabetes status, ethnicity, ischemic time, dialysis, life support measures, and days on waiting list were used for multivariate Cox regression analysis comparing outcomes 6 months before and after UNOS change in allocation system. The pre-UNOS change group had more patients with diabetes (p=0.013). Median time on the wait list was significantly lower following the policy change (35 days vs. 67 days,p < 0.001). In both groups, CHD patients required similar frequencies of IABP, VAD, and ventilator support. During this study period, 23 patients died (14 pre-UNOS change, 9 post-UNOS change). There was a significant increase in the overall post-transplant mortality rate following the new transplant allocation system change (Figure, p=0.01). Compared to pre-UNOS change in allocation system, CHD patients in the new UNOS allocation system have decreased waiting list time but increased mortality. Further study is warranted to better understand these disparities in transplant outcomes since implementation of the new UNOS allocation system.