Donor Recipient Age Research Articles

Donor's long-term quality of life following living-donor lobar lung transplantation.

Living-donor lobar lung transplantation is an alternative procedure to deceased donation lung transplantation. It involves graft donation from healthy donors; however, only a few reports have discussed its long-term prognosis in living lung donors and their associated health-related quality of life. This study aimed to examine living lung donors' health-related quality of life. In our cross-sectional survey of living lung donors, we assessed health-related quality of life-based on three key aspects (physical, mental, and social health) using the 36-Item Short Form Health Survey. We also evaluated chronic postoperative pain and postoperative breathlessness using the numeric rating scale and the modified Medical Research Council Dyspnea scale, respectively. We obtained consent from 117 of 174 living lung donors. The average scores of the living lung donors on the 36-Item Short Form Health Survey were higher than the national average. However, some donors had poorer physical, mental, and social health, with lower summary scores than the national averages. Low mental component summary predictors included donor age (<40 years; odds ratio=10.2; p<.001) and recipient age (<18 years; odds ratio=2.73; p<.032). Low role-social component summary predictors included high lung allocation score (≥50; odds ratio=3.94, p<.002) and recipient death (odds ratio=3.64; p=.005). There were no predictors for a physical component summary. Additionally, many donors did not complain of pain or dyspnea. Living lung donors maintained an acceptable long-term health-related quality of life after surgery. Potential donors should be informed of relevant risk factors, and high-risk donors should receive appropriate support.

The effect of sex inequality on solid organ transplantation: A systematic review and meta-analysis

BackgroundSex disparities are related to biological differences, which may have significant impact on patient and allograft outcomes. The aim was to investigate the impact of sex on clinical and safety outcomes after solid organ transplantation (SOT). MethodsA systematic review and meta-analysis was performed. Observational studies comparing females vs. males after SOT were considered for inclusion after a systematic search of the Pubmed, Cochrane Library, and Web of Science databases conducted from 2016 to 2021. Primary outcome was mortality. PROSPERO register number: CRD42021282615. ResultsAfter retrieving 1103 studies, 22 observational studies (1,045,380 subjects) were finally deemed eligible for inclusion. Females accounted 36.3% of SOT recipients, but presented significantly lower mortality (odds ratio (OR): 0.87, 95% confidence interval (CI): 0.83–0.92, I2=78%). In subgroup analyses, mortality was significantly lower in females undergoing liver (OR: 0.89 95%CI: 0.86–0.92, I2=0%) or kidney transplantation (OR: 0.82 95%CI: 0.76–0.89, I2=72%). Male sex was consistently reported as a protective factor against hospital readmission. Among the outcomes, allograft dysfunction was influenced by a combination of donor-recipient sex and age. Data on overall infections were inconclusive. Several reports suggest a higher risk of malignancy among males. ConclusionsFemales represent one-third of SOT recipients but have higher survival rates than males after liver and kidney transplantation. The impact on graft dysfunction was heterogeneous. While further research is warranted, our findings should encourage clinicians and researchers to consider sex as a factor when taking decisions regarding SOT management.

Endothelial Complications of Hematopoietic Cell Transplantation for Sickle Cell Disease

Introduction Hematopoietic cell transplantation (HCT) is a curative therapy for sickle cell disease (SCD), with especially favorable outcomes in young patients from HLA-identical donors. Unfortunately, HCT is associated with endothelial injury syndromes (EIS), including veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), transplant-associated thrombotic microangiopathy (TA-TMA), and also acute graft-versus-host disease (GVHD), that increase transplant risk. This is further complicated by hemolysis-mediated endothelial dysfunction in patients with SCD. The impact of EIS in this population is not certain. We thus sought to better evaluate endothelial complications of HCT for SCD in a large, international registry. Methods We examined de-identified records of HCT for SCD that were retrieved from data on patients transplanted between 1991 and 2020 in the United States submitted to the Center for International Blood and Marrow Transplant Research (CIBMTR) obtained through curesickle.org. Patients were followed longitudinally until death, loss to follow-up, or last contact through June 2021 at 3, 6, 12, and 24 months after HCT, and then every 2 years. Donors included HLA-matched siblings, haploidentical relatives, and HLA-matched and HLA-mismatched unrelated donors. We examined overall survival, event-free survival, and acute and chronic GVHD. Cox regression models were used to examine for risk factors associated with TMA and VOD. In addition, one-factor (univariate) analysis was used to identify factors associated with higher risk complications. Results A total of 1641 unique patients underwent a first allogeneic HCT between 1991 and 2020, with a median year of HCT of 2014. Of HCT recipients, 67.7% were below the age of 18 years at HCT and 74.7% had Karnofsky performance score ≥ 90. Acute GVHD grades II-IV developed in 18.3% and 22.3% developed chronic GVHD. Graft failure was reported in 17.6% following HCT, which was from an HLA-identical sibling in 61.5%, mismatched relative in 17.6%, matched unrelated donor in 10.2%, and mismatched unrelated donor in 10.7%. Conditioning regimen was myeloablative (50.8%), reduced intensity (23%), or non-myeloablative (22.3%). Patients were followed for a median of 47.8 months (0.3 - 312.9), with 3-year overall survival 91.2% and 3-year event-free survival 85.2%. Median time to death was 9.6 months for 152 patients. Estimated hazard ratio (HR) of death in 7/8 vs. 8/8 HLA matching was 1.5 (95% CI: 0.752, 2.445), which was not statistically significant. However, HR of death for ≤ 6/8 vs. 8/8 HLA matching was 1.7 (95% CI: 1.215, 2.445), indicating a statistically significant increased risk of death. TA-TMA was reported in 27 patients at a median of 2.8 months post-HCT. Univariate analysis of risk factors for TA-TMA indicated increasing incidence with the year of HCT. Age at HCT, HLA matching, and conditioning regimen intensity were not significantly associated. VOD was reported in 24 cases; Cox proportional hazards analysis indicated decreasing incidence with year of HCT. Estimated HR for VOD of patients who developed grade II-IV AGVHD group was 2.965, (95% C.I. 1.089, 8.074). Age at HCT, conditioning intensity, and donor type were not significant. Acute and chronic GVHD were associated with recipient age > 10 years and donors other than HLA-matched siblings; non-myeloablative conditioning was protective against GHVD development. Conclusion Incidence of endothelial complications following HCT for SCD is low, although TA-TMA has been increasingly recognized in recent years. VOD has been observed less frequently over time and correlates with acute GVHD. Donor type, recipient age, and conditioning intensity have the greatest impact on GVHD development.

The strategy of diminishing age gap effect on different donor-recipient combinations in living donor kidney transplantation.

The disparity between kidney donation and the number of uremic patients on the waiting list has increased the demand for older live-donor kidneys (OLK). However, the donor-recipient age gap may have an impact on the recipient's outcome. Patients who underwent living donor kidney transplantation at our institute between 2005 and 2019 were enrolled and categorized into four donor-recipient groups according to age (≥50 years and <50 years). The Estimated Post-Transplant Survival (EPTS) score was used to quantify the recipient's condition. Adjusted models analyzed recipient outcomes and related risks among the four groups. Of the 154 pairs of live donors and recipients, OLK did not influence overall or death-censored graft survival. The four donor-recipient combinations had similar recipient outcomes, except it slightly worsened in the "old donor to young recipient" group. The EPTS score (adjusted HR, 1.02; 95% CI, 1.01-1.04; p = 0.014) and rejection (adjusted HR, 4.26; 95% CI, 1.36-13.37; p = 0.013) were significant risk factors for overall and death-censored graft survival, respectively. Recipients with pretransplant diabetes or prior solid organ transplantation could have amplified risk effects. The main causes of graft loss were death in older recipients and chronic rejection in younger recipients. OLK is safe for young recipients. Nevertheless, adequate immunosuppression should be maintained to prevent rejection and subsequent graft loss, especially for those receiving second kidney transplantation. In contrast, older recipients should avoid overt immunosuppression and control their comorbidities, such as diabetes-related complications to improve their long-term outcomes.

Expanded Criteria Donor With Severe Acute Kidney Injury: Worth to Use?

Expanded criteria donors (ECDs) may present with acute kidney injury (AKI). Many transplantation centers refuse to use these kidneys because of concerns about poor transplant outcomes, resulting in a high discard rate. However, long-term results of ECDs with AKI (ECDs+AKI) have not been extensively studied. We retrospectively compared outcomes of ECDs with ECDs+AKI. Primary outcome was 5-year allograft and patient survival rate. Secondary outcomes were allograft function, rates of delayed graft function, and allograft rejection. Of 743 deceased donor kidney transplant recipients, 95 ECD cases were included in this study. There were 38 patients (40%) with ECDs and 57 patients (60%) with ECDs+AKI. Mean donor creatinine was progressively higher with severity of AKI. Five-year graft and patient survival were comparable between ECDs and ECDs+AKI (80.6% vs 81.1%, P=.95 and 91.7% vs 88.7%, P=.73). Mean (SD) allograft estimated glomerular filtration rate was 36.7 (14.5) vs 40.6 (22.7) mL/min/1.73 m2 with P=.61, respectively. Multivariate analysis showed factors associated graft loss were delayed graft function (P=.01) and donor-recipient age difference ≥10 years (P=.038), not AKI status. Kidney transplant from ECDs+AKI has comparable allograft survival with ECDs without AKI. Use of ECDs+AKI is worthwhile and kidneys from ECDs+AKI should not be discarded. Recipient selection and perioperative care are important to optimize the use of scarce resource.

Graft Rejection and Survival in Patients Undergoing Multi-Organ Heart Transplantation

Purpose Graft rejection and related complications remain leading causes of death in heart transplantation. Here we compare rates of graft rejection and survival in the following transplantation groups: heart-only, heart-lung, heart-kidney, and heart-liver. Methods Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed heart transplants performed from January 1988 to September 2020. Graft survival was assessed with Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were performed to assess hazard ratios. Rejection rates were compared with logistic regression. Results A total of 80,058 patients were included in this study. We found increased risk of graft failure in heart-lung patients and reduced risk in heart-kidney and heart-liver transplants: HR 1.87 (95% 1.75-1.99, p <0.001), HR 0.89 (95% 0.82-0.96, p <0.01), and 0.80 (95% 0.66-0.98, p <0.05), respectively. Rejection rates were lowest in heart-liver transplants, followed by heart-kidney, and heart-lung transplants: OR 0.88 (95% 0.85-0.92, p <0.001), OR 0.91 (95% 0.9-0.93, p <0.001), and OR 0.96 (95% 0.93-1, p <0.05), respectively. These results were consistent in multivariate analysis. Adjusting for donor age, recipient age, and ethnicity found increased risk of graft failure in heart-lung recipients while heart-kidney and heart-liver recipients possessed lower risk: HR 2.01 (95% 1.88-2.14, p <0.001), HR 0.84 (95% 0.78-0.91, p<0.001), and HR 0.80 (95% 0.65-0.97, p <0.05), respectively. Conclusion Heart-lung graft survival is significantly depressed in relation to all other examined groups. Rejection rates are lowest in heart-liver transplants, though all multi-organs showed reduced risk relative to heart-only transplants. More studies are needed to account for confounding and validate these findings prospectively. Graft rejection and related complications remain leading causes of death in heart transplantation. Here we compare rates of graft rejection and survival in the following transplantation groups: heart-only, heart-lung, heart-kidney, and heart-liver. Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed heart transplants performed from January 1988 to September 2020. Graft survival was assessed with Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were performed to assess hazard ratios. Rejection rates were compared with logistic regression. A total of 80,058 patients were included in this study. We found increased risk of graft failure in heart-lung patients and reduced risk in heart-kidney and heart-liver transplants: HR 1.87 (95% 1.75-1.99, p <0.001), HR 0.89 (95% 0.82-0.96, p <0.01), and 0.80 (95% 0.66-0.98, p <0.05), respectively. Rejection rates were lowest in heart-liver transplants, followed by heart-kidney, and heart-lung transplants: OR 0.88 (95% 0.85-0.92, p <0.001), OR 0.91 (95% 0.9-0.93, p <0.001), and OR 0.96 (95% 0.93-1, p <0.05), respectively. These results were consistent in multivariate analysis. Adjusting for donor age, recipient age, and ethnicity found increased risk of graft failure in heart-lung recipients while heart-kidney and heart-liver recipients possessed lower risk: HR 2.01 (95% 1.88-2.14, p <0.001), HR 0.84 (95% 0.78-0.91, p<0.001), and HR 0.80 (95% 0.65-0.97, p <0.05), respectively. Heart-lung graft survival is significantly depressed in relation to all other examined groups. Rejection rates are lowest in heart-liver transplants, though all multi-organs showed reduced risk relative to heart-only transplants. More studies are needed to account for confounding and validate these findings prospectively.

Improvement in Heart Transplant Outcomes: From Medicare Flagging to Best in the World

<h3>Purpose</h3> SRTR data has recently published that the University of Chicago Medical Center (UCMC) heart transplant (HTx) program possesses the highest one-year survival in the world despite being flagged in the past by Medicare. We assessed UCMC's HTx patient outcomes compared to those from other centers in the United States before and after 2015. <h3>Methods</h3> Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed heart transplants performed from January 1988 to September 2020. Re-transplants and multi-organ transplants were excluded. Survival was assessed with Kaplan-Meier method and compared by log-rank test. Univariate and multivariate cox regression analyses were performed to assess hazard ratios. <h3>Results</h3> A total of 69,174 patients were included in this study. Pre-2015, 1-year survival was 84.9% (95% CI 81.3-88.7) at UCMC versus 86.7% (95% CI 86.5-87) at other centers. Cox regression analyses found a trend towards greater risk for mortality in UCMC patients, HR 1.16 (95% CI 0.88-1.52, p = 0.286). These results were consistent in multivariate analysis adjusting for donor age and recipient age. Post-2015, 1-year survival was 95.7% (95% CI 92.4-99.1) versus 91.8% (95% CI 91.4-92.3) at other centers. Cox regression analyses showed a trend towards reduced hazard for mortality in UCMC patients, HR 0.49 (95% CI 0.22-1.10, p = 0.086). Relative to itself, there was a significant improvement in 1-year survival between the two time periods at UCMC, HR 0.25 (95% CI 0.11-0.59, p = 0.001). <h3>Conclusion</h3> There has been a large improvement in HTx outcomes at UCMC, accompanied by a restructuring and refinement of program practices in the year 2015. One-year survival at UCMC has gone from underperforming relative to other centers in the country to enjoying the highest survival in the nation.

Cross-Organ Survival in Patients Undergoing Multi-Organ Cardiac Transplantation

<h3>Purpose</h3> Multi-organ cardiac (i.e., heart-X) transplantation indications have increased as analyses suggest comparable outcomes to patients undergoing single-organ procedures. Here, we present a comparison between survival outcomes in three of the most prevalent multi-organ procedures: heart-lung, heart-kidney, and heart-liver transplantation. <h3>Methods</h3> Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed heart transplants performed from January 1988 to September 2020. Heart-pancreas and triple-organ transplants were excluded due to insufficient sample size. Survival was assessed with Kaplan-Meier method and compared by log-rank test. Univariate and multivariate cox regression analyses were performed to assess hazard ratios. <h3>Results</h3> A total of 80,058 patients were included in this study. Heart-lung transplant recipients experienced significantly worse survival compared to those receiving heart-kidney, heart-liver, or heart-only transplants (p <0.0001). Cox regression analyses found an increased risk for mortality in heart-lung transplants, HR 1.91 (95% CI 1.79-2.04, p <0.001). Multivariate analysis adjusting for donor age, recipient age, and ethnicity found increased risk for mortality in heart-lung transplants and reduced risk in heart-kidney transplants, HR 2.15 (95% CI 2.01-2.29, p <0.001) and HR 0.86 (95% CI 0.8-0.93, p <0.001), respectively. Higher donor or recipient age and African American ethnicity were associated with worse outcomes. <h3>Conclusion</h3> Patients undergoing heart-lung transplantation have poorer outcomes, while heart-liver and heart-kidney transplants display improved rates of survival relative to heart-only transplants. Further research should be performed to validate these findings prospectively and account for confounding.

Oh to Be Young at Heart - Patterns and Implications of Extreme Age Mismatch in Heart Transplantation

<h3>Purpose</h3> While donor recipient age mismatch is common in heart transplantation, the distribution patterns and implications of extreme age mismatch are not well described. We also explored differences in age mismatch related to 2018 changes in adult criteria. <h3>Methods</h3> UNOS data from 1/1/2000 - 9/4/2020 was analyzed. Recipient and donor characteristics and fixed term graft survival were recorded. Ages (years) were categorized - Group 1 = 0-9, 2 = 10-17, 3 = 18-29, 4 = 30-49, 5 = 50-59, 6 = 60+. Groups 5/6 were deemed "older adults". Two sample Z test of proportions was used to compare graft survivals for selected cohorts. Chi-square was used to compare gender data. <h3>Results</h3> 15.4% of hearts accepted by pediatric recipients are from adult donors; 6.7% of hearts accepted by adult recipients are from pediatric (ped) donors. Ped recipients accept 2.8% of adult organs; adult recipients account for 31.2% of accepted ped donors. There is no difference in allocation of ped donors to adult recipients before/after 2018 adult status changes (p=0.42). <i>Extreme age mismatch:</i> 98% of listings for older adults include ped donors in age criteria; ped donors account for 5.8% of accepted donors for this group. Older adults taking ped hearts are more likely to be female (+10%, p=0.0001) and are more likely to accept male donors (+6.5%, p=0.0001). These recipients taking ped hearts are of lower listing status than their counterparts that accept adult hearts. There is no difference in 1 yr or 10 yr graft survival for ped donors with ped recipients vs older adult recipients (1 yr: 89.6% vs 91.2%, p=0.16, 10 yr: 58.2% vs 57.4%, p = 0.65). Older adults have better survival with ped donors vs adult, 57.4% vs 53.4%, p = 0.01. Extreme age mismatch accounts for 3.3% of heart transplants. <h3>Conclusion</h3> Older adults taking ped hearts are more likely to be female than those taking adult hearts and tend to accept a higher proportion of male donors. There is no significant difference in 1 or 10 yr graft survival for ped hearts that go to ped recipients compared to older adult recipients.

The New French Heart Allocation System Has Improved Access to Transplantation in Adolescents

<h3>Purpose</h3> The French allocation system launched on January 2018 introduced donor-recipient age matching. The allocation score decreases linearly from 100% to 0% for candidates 15 to 40 years older than the donor. The aim of this study was to evaluate the effect of the new system on waitlist outcomes in pediatric heart candidates. <h3>Methods</h3> All candidates registered on the national waiting list before 18 years old between January 2010 and December 2020 were included in this cohort study using the national registry Cristal. Waitlist outcomes of the candidates registered before (2010-2017, n=266) and after (2018-2020, n=99) implementation of the new system were compared. The main outcomes were cumulative incidences of transplantation and waitlist mortality or delisting for worsening medical condition. Cumulative incidences were estimated using competing risk analyses with transplantation and death or delisting for worsening medical condition as the competing events. <h3>Results</h3> During the study period 365 listings in 358 candidates resulted in 274 heart transplantations. Among the 365 transplant candidates (195 males, 11+ years n=175, cardiomyopathy n=221, congenital heart disease n=72, retransplantation n=13, other n=59) 179 were CMV-negative, 147 had HLA alloantibodies, 191 were on inotropic infusion, 67 on short-term mechanical circulatory support (MCS) and 41 on long-term MCS at listing. Overall, the 12-month cumulative incidence of transplantation and waitlist mortality was 77% [72-81] and 18% [14-22], respectively. In adolescents the cumulative incidence of transplantation increased after implementation of the new system while waitlist mortality did not change (Figures). In children 0-10 years of age no difference was observed between the 2 periods. <h3>Conclusion</h3> Since the implementation of the new allocation system, access to transplantation has improved in adolescents. Improvement in access to transplantation in younger children requires an expansion of the small children heart donor pool.

Artificial Intelligence 12 Lead ECG Based Heart Age Estimation and 1-year Outcomes After Heart Transplantation

<h3>Purpose</h3> Donor-recipient age differences are known to play a role in post-transplant outcomes with donors >50 or recipients >60 resulting in more complications. Studies to date, however, have not utilized artificial intelligence (AI) based analysis to estimate heart-age in recipients after transplantation. We evaluated the impact of donor heart-age assessment by 12 lead ECG on predicting outcomes within the first year after transplantation with a validated AI model. <h3>Methods</h3> All heart transplant recipients from May 2018 to June 2020 at Mayo Clinic Florida were included. AI based ECG age analysis was performed at time of discharge and 12 months after transplantation. Change in AI ECG heart age was compared to donor and recipient age over time and analyzed for association with rejection or death within the first year after transplant. <h3>Results</h3> A total of 67 patients underwent heart transplantation during our review period. Two patients died prior to hospital discharge and were not included in the analysis. Of the remaining 65 recipients, 45 were male (69%). Median recipient age at transplant was 58 years (IQR 47-64) with a median donor age at transplant of 29 years (IQR 22 -37), p<0.01. Median donor age was 29 years younger than recipient at transplant. One-year survival was 95% with 11 patients treated for rejection during the first year after transplant. The median AI ECG predicted heart age at discharge was 50 years (IQR 41 - 60), which was associated with 1-year survival (p<0.001) and an AUC of .789. At 1 year follow up the AI ECG heart age found 33 patients age had increased to match the recipient age at transplant compared to 27 patients whose AI ECG heart age remained between the donor and recipient age (p = 0.012). Comparing younger (<60) to older recipients (>=60) at transplant correlated with younger AI ECG heart age between the two groups (46 vs 66, p < 0.01) on discharge and at 1 year (50 vs. 61, p<0.01). No significant difference in rejection (p=0.44) or death (p=0.31) between younger or older recipients at 1 year. <h3>Conclusion</h3> 12 lead ECG is a simple noninvasive procedure that can be done easily after transplantation. Our data suggests there may be a signal with AI ECG heart age and one-year endpoints. In an age of publicly reported outcomes, identification of higher risk patients may change practice patterns and improve survival. Larger studies are warranted to evaluate this finding.

Comparative Analyses of Donor-Recipient Age Differences in Adult Cardiothoracic Transplantation: An Analysis of the UNOS/OPTN Database

<h3>Purpose</h3> Broad trends towards increased thoracic organ transplantation in older recipients are well-described. Additionally, usage of older donor organs is well-accepted by many programs. However, little is known about comparative recipient and donor age demographics, and how these may vary with time. <h3>Methods</h3> Using UNOS/OPTN STAR database for both isolated heart (iHTx) and lung transplantation (iLTx) in adults (1988-2017), annual composition of donor organ pool, recipient waitlist pool, and transplanted patient pool, were characterized with respect to age. The 30-day and 1-year recipient survival outcomes are reported. <h3>Results</h3> For iHTx, temporal trends of increased transplantation of older recipients were observed; increased percentages of recipients aged 60-69 and >70 were identified, with decreases in recipients aged 50-59 and 40-49. These trends were identified in iLTx as well, and were more substantial. In both iHTx and iLTx, by 2017, recipients aged 60-69 accounted for the single largest age range undergoing transplantation. However, analysis of survival outcomes from 2010-17 for iHTx (durable continuous flow mechanical circulatory support era), and from 2006-17 for iLTx (lung allocation score era) revealed reduced 30-day and 1-year survival as a function of recipient age, with exception of iLTx in the age 18-29 group. In contrast, no clear temporal trends were observed with respect to donor heart and lung age demographics. Heart and lung donors aged 18-29 accounted for the single largest age range, followed by ages 30-39. <h3>Conclusion</h3> Cardiothoracic transplantation involves a transference of organs from younger to older individuals, and the extent of this has increased more recently. However, older recipients have decreased short-term survival, which likely translates to diminished long-term survival, given a decreased prospective life expectancy even for healthy older individuals. These findings may have implications for organ allocation policies.

B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4+and CD8+ T cells, B cells, and natural killer cells at the time of V1. Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titer. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T cell and B cell counts, ongoing I/C treatment, and a haploidentical donor were characteristic of nonhumoral responders. However, multiparameter analysis showed that B cell aplasia was the sole factor predicting the absence of a specific immune response (odds ratio, 0.01; 95% confidence interval, 0.00 to 0.10; P < 10−3). Indeed, the rate of humoral response was 9.1% in patients with B cell aplasia versus 95.9% in patients with a B cell count >0 (P < 10−9). These results advocate for the administration of anti-SARS-CoV-2 vaccination in allo-HSCT recipients as early as peripheral B cell levels can be detected, and also suggest the need for close monitoring of B-cell reconstitution after Allo-HSCT.

The Effects of Donor-Recipient Age and Sex Compatibility in the Outcomes of Deep Anterior Lamellar Keratoplasties.

PurposeCorneal transplantations are the commonest allogenic transplant surgeries performed worldwide. Transplantable grade donor cornea is a finite resource. There is thus an impetus for eye banks to optimize the use of each harvested cornea, and clinicians to minimize the risks of graft rejection and failure. With better survival and lower rejection rates, anterior lamellar keratoplasty has gained popularity as an alternative technique to full-thickness penetrating keratoplasty, for the treatment of corneal stromal diseases. This study evaluated the effects of donor-recipient age- and sex-matching on the outcomes of eyes that had undergone deep anterior lamellar keratoplasty (DALK) surgeries.DesignObservational cross-sectional study (national corneal graft registry data).SubjectsAll DALK surgeries performed in a tertiary ophthalmic hospital over an 11-year period.MethodsTo analyse the effects of donor-recipient sex-matching, transplantations were classified as “presumed H-Y incompatible” (male donor to female recipient) or “presumed H-Y compatible” (all other donor-recipient sex combinations). For age-matching, differences in donor and recipient ages were calculated. Cox proportional hazards regressions were used to evaluate the influence of donor-recipient sex-matching and age-matching on graft failure and rejection.Main Outcome MeasuresRates of graft failure and rejection within each group.Results401 eyes were included. 271 (67.6%) transplants were presumed H-Y compatible. 29 (7.2%) grafts failed and 9 (2.2%) grafts rejected. There were trends of lower hazard ratios (HRs) in graft failure and rejection in the presumed H-Y compatible group [HRs: 0.59 (95% CI 0.20–1.77, p = 0.34) and 0.93 (95% CI 0.22–3.89, p = 0.926), respectively]. Median difference in age between recipients and donors was 15.0 years (IQR −2.8–34.3). The HRs of graft failure and rejection were not influenced by donor-recipient age [HRs per 1-year increase in age difference: 0.995 (95% CI 0.98–1.01, p = 0.483) and 1.01 (95% CI 0.99–1.03, p = 0.394), respectively].ConclusionIn eyes that had undergone DALK surgeries, no significant influence of donor-recipient sex- or age-matching on graft rejection and failure was observed. Without strong evidence and the limitations of obtaining sample sizes required for an adequately powered study, the benefits of sex- and age-matching of donors and recipients during graft allocation for DALK surgeries is currently inconclusive.

Age-dependent Sex Differences in Graft Loss After Kidney Transplantation.

Sex differences in kidney graft loss rates were reported in the United States. Whether these differences are present in other countries is unknown. We estimated the association between recipient sex and death-censored graft loss in patients of all ages recorded in the Scientific Registry of Transplant Recipients, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study registries who received a first deceased donor kidney transplant (1988-2019). We used multivariable Cox regression models, accounting for the modifying effects of donor sex and recipient age, in each registry separately; results were combined using individual patient data meta-analysis. We analyzed 438 585 patients. Young female patients 13-24 y old had the highest crude graft loss rates (female donor: 5.66; male donor: 5.50 per 100 person-years). Among young recipients of male donors, females showed higher graft loss risks than males (0-12 y: adjusted hazard ratio [aHR] 1.42, (95% confidence interval [CI], 1.17-1.73); 13-24 y: 1.24 (1.17-1.32); 25-44 y: 1.09 (1.06-1.13)). When the donor was female, there were no significant differences by recipient sex among those of age <45 y; however, the aHR for females was 0.93 (0.89-0.98) in 45-59 y-old and 0.89 (0.86-0.93) in ≥ 60 y-old recipients. Findings were similar for all 3 registries in most age intervals; statistically significant heterogeneity was seen only among 13-24-y-old recipients of a female donor (I2 = 71.5%, P = 0.03). There is an association between recipient sex and kidney transplantation survival that is modified by recipient age and donor sex.

Adult Living-Donor Kidney Transplantation, Donor Age, and Donor–Recipient Age

IntroductionOwing to organ shortage, the number of kidney transplantation (KT) involving older adult living donors is increasing. We aimed to investigate the effects of living-donor age and donor-recipient age differences on KT outcomes.MethodsThis single-center, retrospective cohort study involved 853 adult LDKTs performed between January 2008 and December 2018. Recipients were stratified into the following 5 groups based on donor age and donor-recipient age difference: donor age, 30 to 49 years and age difference, −10 to 15 years; donor age, 50 to 69 years and age difference, −10 to 15 years; donor age, 50 to 69 years and age difference, 15 to 40 years; donor age, 70 to 89 years and age difference, −10 to 15 years; and donor age, 70 to 89 years and age difference, 15 to 40 years (groups 1, 2, 3, 4, and 5, respectively). As a primary outcome, the risk of graft loss was investigated. The secondary outcomes were postoperative estimated glomerular filtration rates (eGFRs) and mortality rates of recipients.ResultsGroup 4, representing KT between older adult donors and older adult recipients, had the highest graft loss risk and mortality. The eGFRs of the recipients from donors aged 70 to 89 years (groups 4 and 5) were significantly lower than those from donors in the other groups. Although the differences in the eGFR between groups 4 and 5 were not significant, the eGFR of group 4 was lower than that of group 5 at 6 months post-KT.ConclusionLDKTs from older adult donors to older adult recipients resulted in the worst graft survival and mortality rates.

Higher levels of serum phosphorus are associated with coronary calcification post heart transplantation

Abstract Background A higher serum phosphorus level, although within the normal range has been linked to coronary artery and aortic calcification in the non-transplant population. Coronary calcification is mostly associated with donor-derived lesions, and is uncommon within the first years after heart transplantation. Purpose We aimed to investigate the association of phosphorus levels with plaque calcification after heart transplantation. Methods A total of 156 patients who underwent virtual histology intravascular ultrasound (VH-IVUS) studies for cardiac allograft vasculopathy (CAV) surveillance and had fasting serum phosphorus levels &amp;lt;4.5 mg/dL, were included in the analyses. IVUS analyses were performed in the proximal left anterior descending artery, and plaque composition of dense calcium (DC) was evaluated using VH-IVUS, and presented as percent DC of total plaque volume. The patients were separated into 3 groups according to tertiles of serum phosphorus levels. Results Mean recipient and donor ages were 54±13 and 31±14 years, respectively. Mean serum phosphorus in recipients was 3.5±0.6 mg/dL, with median time after transplantation at the IVUS studies of 6 (3,10) years. There were no significant differences in %DC between phosphorus tertiles in patients who underwent IVUS within 6 years after transplantation (p=0.11, Fig. 1A). However, beyond 6 years after transplantation, we observed an incremental association between phosphorus levels and the extent of calcification (p=0.02, Fig. 1B). In this group, serum phosphorus levels significantly correlated with %DC (standardized β=0.29, P=0.008), and this correlation remained significant after adjustment for donor age, recipient age, and eGFR (standardized β=0.26, P=0.001). Conclusion Higher serum phosphorus levels were associated with a level-dependent increase in calcified coronary artery plaque in patients starting 6 years post heart transplant. Long-term exposure to higher serum phosphorus, even within the normal range, might promote plaque calcification after heart transplantation. Funding Acknowledgement Type of funding sources: None.

Impact of donor telomere length on survival in patients undergoing matched sibling donor transplantation for aplastic anaemia.

Although telomere shortening is seen frequently in patients with aplastic anaemia (AA), there are no data on its association in matched sibling donor (MSD) transplants. We evaluated the effect of pre-transplant telomere length of patients and donors, measured by quantitative real-time polymerase chain reaction in 163 recipients undergoing MSD transplants. The median age of patients and donors was 24 and 26years, respectively. Fludarabine and cyclophosphamide was the main conditioning regimen used and all received peripheral blood stem cell grafts. Engraftment occurred in 89% with graft failure (primary and secondary) in 6%. Acute and chronic graft-versus-host disease (GVHD) occurred in 28% and 24%, respectively. At a median follow-up of 37months, 117 patients (72%) were alive. All patients and donors were divided into short and long telomere length based on their median and quartile values. Patient telomere length was not associated with severity of AA, neutrophil recovery, graft failure, acute GVHD or chronic GVHD. Longer donor telomere length was associated with better overall survival [hazard ratio (HR)=0·2, P=0·006] but did not influence neutrophil recovery, graft failure, acute or chronic GVHD. The five-year overall survival was significantly better (94·9±3·5% vs 65·4±4·3%, P=0·002) for donors with long (highest quartile, DTL-HQ) versus short (lower three quartiles, DTL-LQ) telomeres, respectively. On multivariate analysis, longer donor telomere length, recipient age and acute GVHD continued to remain significant. This is the first study demonstrating an association of donor telomere length on overall survival following MSD transplant for AA but it needs to be confirmed in larger studies.

Practice Patterns in the Acceptance of Medically Complex Living Kidney Donors with Obesity, Hypertension, Family History of Kidney Disease, or Donor-Recipient Age Discrepancy.

Background To assess the practice patterns of the acceptance of medically complex living kidney donors (MCLKDs). Methods We distributed a survey to nephrologists and transplant surgeons (TS) across the world through major international transplant societies. The survey contained questions regarding obesity, abnormal blood glucose profile, mild hypertension, donor-recipient age discrepancy, or family history of kidney disease of unknown etiology. Results In total, 239 respondents from 29 countries (42% were nephrologists and 58% were TS). Most respondents would allow donations from obese donors, especially if they intended to lose weight but would be cautious if these donors had abnormal blood glucose or family history of diabetes mellitus. In hypertensive donors, future pregnancy plans mattered in decisions regarding the acceptance of female donors. Most respondents would allow young donors but would be more cautious if they had a future risk of hypertension or a family history of kidney disease of unknown etiology. They would also allow donations from an older person if prolonged waiting time was anticipated. We found multiple areas of consensus of practice among the diverse members of international transplant societies, with some interesting variations among nephrologists and TS.Conclusions This survey highlights the practice patterns of the acceptance of MCLKDs among the international community. In the absence of clear guidelines, this survey provides additional information to counsel kidney donors with these conditions.

Trends in Early Graft Failure Leading to Regrafting After Endothelial Keratoplasty in the United States.

The purpose of this study was to report trends in the prevalence of early graft failure after endothelial keratoplasty in the United States. Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) graft volumes were collected from records maintained by 6 major eye banks in the United States from January 1, 2013, to December 31, 2018. The prevalence and presumed cause of early graft failures (defined as a graft with persistent edema or regrafted within 8 weeks after keratoplasty) each year were sourced from surgeon-reported adverse events. Failed graft cases from the 3 eye banks were compared with nonfailures at the donor and recipient levels to perform subset analysis of factors associated with early graft failure. A total of 51,887 endothelial keratoplasty tissues were distributed during the study period; 72% were DSAEK grafts. The total number of early graft failures reported was 168 of 14,284 (1.18%) for DMEK and 322 of 37,603 (0.86%) for DSAEK. Early DMEK failures decreased from 2013 (7.69%) to 2018 (0.68%). In generalized linear mixed model analyses adjusting for donor tissue characteristics, recipient age, and diagnosis, an association of borderline significance was found between higher donor age and early failure [odds ratio (95% confidence interval): 1.03 (1.00-1.05); unit change of 1 yr] and DSAEK [odds ratio 1.02 (1.00-1.04); unit of change 1 yr] cases. The proportion of early graft failures in DMEK decreased over time and was comparable with failure rates in DSAEK at the end of the study period. The surgical learning curve might have played a role.