Donor type and 3-month hospital readmission following kidney transplantation: results from the Netherlands organ transplant registry.

BACKGROUND: Hospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs. METHODS: We included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders. RESULTS: Among 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly. CONCLUSION: A lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.

Practice patterns of corneal transplantation in Europe: first report by the European Cornea and Cell Transplantation Registry.

PURPOSE: To report practice patterns of corneal transplantation in Europe. SETTING: Corneal clinics in 10 European member states (MS), the United Kingdom, and Switzerland. DESIGN: Multinational registry study. METHODS: Corneal transplant procedures registered in the European Cornea and Cell Transplantation Registry were identified. Preoperative donor and recipient characteristics, indication and reason for transplantation, and surgical techniques were analyzed. RESULTS: A total of 12 913 corneal transplants were identified from 10 European Union MS, the United Kingdom, and Switzerland. Most countries were self-sufficient with regard to donor tissue. Fuchs endothelial corneal dystrophy was the most common indication (41%, n = 5325), followed by regraft (16%, n = 2108), pseudophakic bullous keratopathy (12%, n = 1594), and keratoconus (12%, n = 1506). Descemet stripping automated endothelial keratoplasty (DSAEK, 46%, n = 5918) was the most commonly performed technique, followed by penetrating keratoplasty (30%, n = 3886) and Descemet membrane endothelial keratoplasty (9%, n = 1838). Vision improvement was the main reason for corneal transplantation (90%, n = 11 591). Surgical technique and reason for transplantation differed between indications. CONCLUSIONS: This report provides the most comprehensive overview of corneal transplantation practice patterns in Europe to date. Fuchs endothelial dystrophy is the most common indication, vision improvement the leading reason, and DSAEK the predominant technique for corneal transplantation.

Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation.

With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor.

Outcomes of corneal transplantation in Europe: report by the European Cornea and Cell Transplantation Registry.

PURPOSE: To analyze real-world graft survival and visual acuity outcomes of corneal transplantation in Europe. SETTING: Corneal clinics in 10 European Union member states, the United Kingdom, and Switzerland. DESIGN: Multinational registry study. METHODS: All corneal transplant procedures registered in the European Cornea and Cell Transplantation Registry (ECCTR) were identified. Graft survival of primary corneal transplants were analyzed using Kaplan-Meier survival curves with log-rank test and Cox regression. Corrected distance visual acuities (CDVAs) are reported at baseline and 2 years postoperatively using the Lundström distribution matrix. RESULTS: A total of 12 913 corneal transplants were identified. Overall, 32-year graft survival of corneal transplants was high (89%) but differed between indications, ranging from 98% in keratoconus and 80% for trauma. Overall, CDVA improved postoperatively, but the risk for losing vision ranged from 7% (baseline vision ≤0.1 Snellen) to 58% (baseline vision ≥1.0 Snellen). CONCLUSIONS: This report provides a comprehensive overview of graft survival and visual outcomes of corneal transplantation in Europe. In addition, it provides real-world estimates of outcomes for a variety of indications and surgical techniques to support benchmarking and demonstrates the relationship between baseline and postoperative vision.

Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry.

BACKGROUND: Cold ischemia time (CIT) is known to impact kidney graft survival rates. We compare the impact of CIT on graft failure and mortality in circulatory death versus brain death donor kidneys and how it relates to donor age. METHODS: We used the prospective Dutch Organ Transplantation Registry to include 2153 adult recipients of brain death (n = 1266) and circulatory death (n = 887) donor kidneys after static cold storage from transplants performed between 2005 and 2012. CIT was modeled nonlinearly with splines. Associations and interactions between CIT, donor type, donor age, 5-year (death-censored) graft survival, and mortality were evaluated. RESULTS: The median CIT was 16.2 hours (interquartile range 12.8-20), ranging from 3.4 to 44.7 hours for brain death and 4.7 to 46.6 hours for circulatory death donor kidneys. At >12 hours of CIT, we observed an increased risk of graft failure in kidneys donated after circulatory death versus after brain death. This risk rose significantly at >22 hours of CIT (hazard ratio 1.45; 95% confidence interval, 1.01-2.49; P = 0.043). Kidneys that came from 60-year-old circulatory death donors demonstrated elevated hazard risk at 19 hours of CIT, a shorter timeline than that for kidneys that came from brain death donors of the same age (hazard ratio 1.33; 95% confidence interval, 1.00-1.78; P = 0.045). The additional harmful effects of increased CIT in kidneys from circulatory-death donors were also found for death-censored graft failure but did not affect mortality rates in any significant way. CONCLUSIONS: The findings support the hypothesis that prolonged cold ischemia is more harmful for circulatory death donor kidneys that have already been subjected to a permissible period of warm ischemia. Efforts should be made to reduce CIT, especially for older circulatory death donor kidneys.

Prediction models for delayed graft function: external validation on The Dutch Prospective Renal Transplantation Registry.

Background: Delayed graft function (DGF) is a common complication after kidney transplantation in the era of accepting an equal number of brain- and circulatory-death donor kidneys in the Netherlands. To identify those cases with an increased risk of developing DGF, various multivariable algorithms have been proposed. The objective was to validate the reproducibility of four predictive algorithms by Irish et al. (A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant 2010;10:2279-2286) (USA), Jeldres et al. (Prediction of delayed graft function after renal transplantation. Can Urol Assoc J 2009;3:377-382) (Canada), Chapal et al. (A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors. Kidney Int 2014;86:1130-1139) (France) and Zaza et al. (Predictive model for delayed graft function based on easily available pre-renal transplant variables. Intern Emerg Med 2015;10:135-141) (Italy) according to a novel framework for external validation. Methods: We conducted a prospective observational study with data from the Dutch Organ Transplantation Registry (NOTR). Renal transplant recipients from all eight Dutch academic medical centers between 2002 and 2012 who received a deceased allograft were included (N = 3333). The four prediction algorithms were reconstructed from donor, recipient and transplantation data. Their predictive value for DGF was validated by c-statistics, calibration statistics and net benefit analysis. Case-mix (un)relatedness was investigated with a membership model and mean and standard deviation of the linear predictor. Results: The prevalence of DGF was 37%. Despite a significantly different case-mix, the US algorithm by Irish was best reproducible, with a c-index of 0.761 (range 0.756 - 0.762), and well-calibrated over the complete range of predicted probabilities of having DGF. The US model had a net benefit of 0.242 at a threshold probability of 0.25, compared with 0.089 net benefit for the same threshold in the original study, equivalent to correctly identifying DGF in 24 cases per 100 patients (true positive results) without an increase in the number of false-positive results. Conclusions: The US model by Irish et al. was generalizable and best transportable to Dutch recipients with a deceased donor kidney. The algorithm detects an increased risk of DGF after allocation and enables us to improve individual patient management.

Performance of an easy-to-use prediction model for renal patient survival: an external validation study using data from the ERA-EDTA Registry.

Background: An easy-to-use prediction model for long-term renal patient survival based on only four predictors [age, primary renal disease, sex and therapy at 90 days after the start of renal replacement therapy (RRT)] has been developed in The Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in 10 European countries. Methods: Data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period 1995-2005 were included. Patients <16 years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10- (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes. Results: We used a data set of 136 304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with some small variation on the country level. The concordance index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75. Conclusions: A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.

Validation of the Prognostic Kidney Donor Risk Index Scoring System of Deceased Donors for Renal Transplantation in the Netherlands.

BACKGROUND: The prognostic Kidney Donor Risk Index (KDRI)-developed and internally validated in the United States-is a widely used tool to predict transplant outcome of a deceased donor kidney. The KDRI is currently used for longevity matching between donors and recipients in the United States. METHODS: We aimed to externally validate the KDRIdonor-only and KDRIfull as proposed by Rao et al (2009). KDRIdonor-only consist of 10 donor factors, and KDRIfull with an additional 4 transplant factors. We used the Dutch Organ Transplantation Registry to include 3201 adult recipients transplanted from 2002 to 2012. RESULTS: The median Dutch KDRI was 1.21 and comparable with the year 2012 in the United States (median of 1.24). The calibration-slope was 0.98 and 0.96 for the KDRIfull and KDRIdonor-only, respectively, indicating that predictions of graft failure were on average similar. The discriminative ability (Harrell C) of the KDRIfull and the KDRIdonor-only at 5 years was 0.63 (95% confidence interval [CI], 0.62-0.64), and 0.62 (95% CI, 0.61-0.63), respectively. We found misspecification of 3 KDRI factors: age (P = 0.002), weight (P = 0.017), and cold ischemia time (P < 0.001). Adding the use of inotropic drugs before donation (P = 0.040) and the interaction between circulatory-death donor kidneys and prolonged cold ischemic time (>24 hours vs 12 hours; P = 0.059) could improve predictive ability. CONCLUSIONS: The KDRI performs equal in the Dutch population. Discriminative ability of the KDRI indicates limited clinical use for adequate individualized decisions. An updated KDRI may contribute to a standardized policy meeting the growing demand of donor kidneys in the Eurotransplant region.

Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death-A Dutch Cohort Study.

BACKGROUND: Organ shortage persists despite a high rate of donation after circulatory death (DCD) in the Netherlands. The median waiting time for a deceased donor kidney in 2013 was 3.5 years. Most DCD kidneys are from controlled DCD (cDCD; Maastricht category III). Experience with uncontrolled donors after cardiac death (uDCD), that is, donors with an unexpected and irreversible cardiac arrest (Maastricht categories I and II), is increasing; and its effect on transplant outcomes needs evaluation. METHODS: We used the Dutch Organ Transplantation Registry to include recipients (≥18 years old) from all Dutch centers who received transplants from 2002 to 2012 with a first DCD kidney. We compared transplant outcome in uDCD (n = 97) and cDCD (n = 1441). RESULTS: Primary nonfunction in uDCD was higher than in the cDCD (19.6% vs 9.6%, P < 0.001, respectively). Delayed graft function was also higher in uDCD than in cDCD, but not significantly (73.7% vs 63.3%, P = .074, respectively). If censored for primary nonfunction, estimated glomerular filtration rates after 1 year and 5 years were comparable between uDCD and cDCD (1 year: uDCD, 44.3 (23.4) mL/min/m and cDCD, 45.8 (24.1) mL/min/m; P = 0.621; 5 years: uDCD, 49.1 (25.6) mL/min/m and cDCD, 47.7 (21.7) mL/min/m; P = 0.686). The differences in primary nonfunction between kidneys from uDCD and cDCD were explained by differences in the first warm ischemic period, cold ischemic time, and donor age. CONCLUSIONS: We conclude that uDCD kidneys have potential for excellent function and can constitute a valuable extension of the donor pool. However, further efforts are necessary to address the high rate of primary nonfunction.

Stretching the Limits of Renal Transplantation in Elderly Recipients of Grafts from Elderly Deceased Donors.

An increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002-2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type. In multiple logistic regression analysis, elderly recipients of elderly DCD kidneys experienced more delayed graft function and acute rejection than did elderly recipients of young DBD kidneys (odds ratios 10.43 [95% confidence interval (95% CI), 5.75 to 18.91] and 2.78 [95% CI, 1.35 to 5.73], respectively). In Cox regression analysis, elderly recipients of elderly DCD kidneys had a 5-year mortality risk higher than that of elderly recipients of young DBD kidneys (hazard ratio, 1.86; 95% CI, 1.15 to 3.02). Elderly recipients of elderly kidneys had a 5-year mortality rate comparable to that of waitlisted elderly patients remaining on dialysis. Among elderly recipients, 63.8% of those who received elderly DCD kidneys, 45.5% of those who received elderly DBD kidneys, and approximately 26% of those who received young DBD or DCD kidneys had an eGFR<30 ml/min per 1.73 m2 (including primary nonfunction) after 1 year. In conclusion, improving donor selection and preservation is warranted if the allocation of elderly DCD grafts to elderly recipients is to be expanded.

The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent.

Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were 'donor found' and 'transplantation reached'. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P<0.0001). Non-Northwestern European patients more often needed a cord blood transplant. The degree of HLA matching was significantly lower for non-Northwestern European patients (P<0.0006). The time needed to identify a donor decreased for both populations. The percentage of Northwestern European patients reaching transplantation increased from 77% to 83% and for non-Northwestern European patients from 57% to 72% (P=0.0003). The increase of the global inventory resulted in more transplants for patients lacking a family donor, although the quality and quantity of (potential) haematopoietic cell grafts for patients of a non-Northwestern European descent remained inferior, indicating the need for adaptation of recruitment.

Improved Mortality Prediction in Dialysis Patients Using Specific Clinical and Laboratory Data.

BACKGROUND: Risk prediction models can be used to inform patients undergoing renal replacement therapy about their survival chances. Easily available predictors such as registry data are most convenient, but their predictive value may be limited. We aimed to improve a simple prediction model based on registry data by incrementally adding sets of clinical and laboratory variables. METHODS: Our data set includes 1,835 Dutch patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. The potential survival predictors were categorized on availability. The first category includes easily available clinical data. The second set includes laboratory values like albumin. The most laborious category contains glomerular filtration rate (GFR) and Kt/V. Missing values were substituted using multiple imputation. Within 1,225 patients, we recalibrated the registry model and subsequently added parameter sets using multivariate Cox regression analyses with backward selection. On the other 610 patients, calibration and discrimination (C-index, integrated discrimination improvement (IDI) index and net reclassification improvement (NRI) index) were assessed for all models. RESULTS: The recalibrated registry model showed adequate calibration and discrimination (C-index=0.724). Adding easily available parameters resulted in a model with 10 predictors, with similar calibration and improved discrimination (C-index=0.784). The IDI and NRI indices confirmed this, especially for short-term survival. Adding laboratory values resulted in an alternative model with similar discrimination (C-index=0.788), and only the NRI index showed minor improvement. Adding GFR and Kt/V as candidate predictors did not result in a different model. CONCLUSION: A simple model based on registry data was enhanced by adding easily available clinical parameters.

Survival prognosis after the start of a renal replacement therapy in the Netherlands: a retrospective cohort study.

BACKGROUND: There is no single model available to predict the long term survival for patients starting renal replacement therapy (RRT). The available models either predict survival on dialysis until transplantation, survival on the transplant waiting list, or survival after transplantation. The aim of this study was to develop a model that includes dialysis survival and survival after an eventual transplantation. METHODS: From the Dutch renal replacement registry, patients of 16 years of age or older were included if they started RRT between 1995 and 2005, still underwent RRT at baseline (90 days after the start of RRT) and were not registered at a non-renal organ transplant waiting list (N = 13868). A prediction model of 10-year patient survival after baseline was developed through multivariate Cox regression analysis, in one half of the research group. Age at start, sex, primary renal disease (PRD) and therapy at baseline were included as possible predictors. A sensitivity analysis has been performed to determine whether listing on the transplant waiting list should be added. The predictive performance of the model was internally validated. Calibration and discrimination were computed in the other half of the research group. Another sensitivity analysis was to assess whether the outcomes differed if the model was developed and tested in two geographical regions, which were less similar than the original development and validation group. No external validation has been performed. RESULTS: Survival probabilities were influenced by age, sex, PRD and therapy at baseline (p < 0.001). The calibration and discrimination both showed very reasonable results for the prediction model (C-index = 0.720 and calibration slope for the prognostic index = 1.025, for the 10 year survival). Adding registration on the waiting list for renal transplantation as a predictor did not improve the discriminative power of the model and was therefore not included in the model. CONCLUSIONS: With the presented prediction model, it is possible to give a reasonably accurate estimation on the survival chances of patients who start with RRT, using a limited set of easily available data.

[Causes of decreased use of peritoneal dialysis as a kidney replacement therapy in the Netherlands]. / Oorzaken voor verminderd aandeel peritoneale dialyse als niervervangende behandeling in Nederland.

OBJECTIVE: To study the extent and causes of the declining use of peritoneal dialysis (PD) as kidney replacement therapy in patients with end-stage renal disease in the Netherlands. DESIGN: Retrospective cohort study. METHOD: The prevalence and incidence of various kidney replacement therapies in the Netherlands from 1995 to 2010 were analysed. Also the 5-year outflow of patients on PD or haemodialysis (HD) from 1995 to 2006 was analysed using the cumulative incidence competing risks method and Cox regression analysis. RESULTS: The absolute number of patients starting PD between 1995 and 2008 was stable at about 400 per year. There was a relative decline in the use of PD in the total dialysis population from 15% in 1995 to 8% in 2010. This decrease was seen in both large and small centres and was related to a relative increase in the numbers undergoing HD (67% before 2001, 74% in 2009), and kidney transplantation before dialysis (3% before 2002, 9% in 2009), as well as a decrease in change of therapy from HD to PD. The increased number starting on HD was associated with the growth of the incident patient group aged 65 years or older, most of whom (80-85%) underwent HD. Within the younger group (0-65 years) there was an increase in numbers on HD and in the number of pre-emptive transplantations. CONCLUSION: The decline in the prevalence of PD was partly explained by the relative increase in numbers starting HD, associated with an ageing patient population, fewer people changing from HD to PD therapy, and the increased number of kidney transplantations before dialysis in younger patients. The increasing prevalence of HD has been made possible by growth of the HD capacity.

Kidney transplantation from donors after cardiac death: a 25-year experience.

BACKGROUND: The shortage of organ donors presents a major obstacle for adequate treatment of patients with end-stage renal disease. Donation after cardiac death (DCD) has been shown to increase the number of kidneys available for transplantation. The present article reports on the first 25 years of our experience with DCD kidney transplantation. METHODS: This observational cohort study included all DCD kidney transplantations recovered in our procurement area from January 1, 1981 until December 31, 2005 (n=297). Patients were followed up until the earliest of death or December 31, 2006. Clinical outcomes were compared with matched kidney transplantations from brain dead donors (DBD, n=594), using multivariable regression models to adjust for potential confounders. RESULTS: DCD activity resulted in a 44% increase in the number of deceased donor kidneys from our organ procurement area. After adjustment for potential confounders, the odds of primary nonfunction and delayed graft function were 7.5 (95% CI, 4.0-14.1; P<0.001) and 10.3 (95% CI, 6.7-15.9; P<0.001) times greater, respectively, for DCD kidneys compared with DBD kidneys. The high incidence of primary nonfunction of DCD kidneys resulted in an increased rate of graft loss (HR, 1.82; 95% CI, 1.37-2.42; P<0.001). However, DCD kidneys that did not experience primary nonfunction functioned as long as DBD kidneys (HR, 1.05; 95% CI, 0.73-1.51; P=0.79). Patient survival of DCD and DBD kidney recipients was equivalent (HR, 1.16; 95% CI, 0.87-1.54; P=0.32). CONCLUSIONS: The benefits of DCD kidney transplantation outweigh the increased risk of early graft loss. Expansion of the supply of DCD kidneys is likely to improve the treatment of wait-listed dialysis patients.

Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors.

Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.

Non-heart-beating lung donation: how big is the pool?

Lungs from non-heart-beating (NHB) donors are seldom used in The Netherlands despite the good quality of these organs. Based on a retrospective analysis of 162 NHB donor procedures we found that only 5% of the lungs were actually utilized, but that 30% of the lungs were suitable for transplantation. Not recognizing the suitability of NHB lungs is likely the main reason for their non-availability.

Allogeneic MHC class I molecules with numerous sequence differences do not elicit a CTL response.

CD8+ T cell-mediated alloreactivity is generally believed to involve recognition of the alpha1/alpha2 domains of donor-type class I MHC molecules as well as the peptides they bind. Using the CTLp assay outcome as a parameter for the induction of alloreactivity, we have retrospectively surveyed 80 haematopoietic stem cell donor/patient pairs that feature a range of allelic differences at single HLA-A, -B, and -C loci in an attempt to probe the predictive value of such mismatches. In contrast to the expectation that greater degree of allelic disparity would lead to more alloreactivity, we found that in a substantial number of cases, class I MHC molecules with numerous sequence differences did not elicit an allogeneic CTL response. We propose that in generating a T cell repertoire with a sufficiently narrow responsive for self-MHC, positive thymic selection limits the capacity to recognize allogeneic MHC molecules whose structure and sequence have diverged extensively. These findings are important for donor and patient MHC matching strategies and our understanding of T cell-MHC interaction after haematopoietic stem cell transplantation.