High Risk Of Graft Rejection Research Articles

Autologous Contralateral and Ipsilateral Rotational Penetrating Keratoplasty - A Case Series and Mini-Review.

Corneal stromal opacities can severely impact visual acuity if they are located in the visual axis. Homologous penetrating keratoplasty (HPK) is usually the preferred surgical option in such clinical circumstances. However, autologous penetrating keratoplasty (APK) could be an immunologically safer alternative. The purpose of this study was to report the surgical technique, indications, and (dis)advantages of ipsilateral rotational and contralateral APK, as well as pre- and postoperative clinical findings of four patients who underwent contralateral APK. In ipsilateral rotational APK, eccentric trephination places the central corneal opacity at the excision edge, whereafter the corneal button is rotated to clear the visual axis. Contralateral APK is suitable for more specific clinical situations with corneal opacity in a functionally much better eye. Clear cornea of the (almost) blind eye suffering from a noncorneal pathology is transplanted to the potentially better seeing eye suffering from a corneal pathology, followed by HPK in the (almost) blind donor eye. After 18 months, potentially better-seeing eyes improved from logMAR 1.3 to 0.6 in visual acuity, with most HPK-treated weaker eyes matching preoperative levels. Considering ipsilateral rotational and contralateral APK before moving on straight towards HPK is crucial in select cases. Autologous contralateral keratoplasty should be preferred for patients with (1) corneal scars in a potentially better seeing eye and (2) a clear cornea in an (almost) blind eye, especially in cases of high risk for graft rejection.

Neoadjuvant and adjuvant systemic therapy in HCC: Current status and the future.

Surgical therapies in patients with early-stage HCC can afford long-term survival but are often limited by the continued risk of recurrence, underscoring an interest in (neo)adjuvant strategies. Prior attempts at adjuvant therapy using tyrosine kinase inhibitors failed to yield significant improvements in recurrence-free survival or overall survival. Advances in the efficacy of systemic therapy options, including the introduction of immune checkpoint inhibitors, have fueled renewed interest in this area. Indeed, the IMBrave050 trial recently demonstrated significant improvements in recurrence-free survival with 1 year of adjuvant atezolizumab plus bevacizumab in high-risk patients undergoing surgical resection or ablation, with several other ongoing trials in this space. There is a strong rationale for consideration of the administration of these therapies in the neoadjuvant setting, supported by early clinical data demonstrating high rates of objective responses, although larger trials examining downstream outcomes are necessary, particularly considering the possible risks of this strategy. In parallel, there has been increased interest in using systemic therapies as a bridging or downstaging strategy for liver transplantation. Current data suggest the short-term safety of this approach, with acceptable rates of rejection, so immunotherapy is not considered a contraindication to transplant; however, larger studies are needed to evaluate the incremental value of this approach over locoregional therapy. Conversely, the use of immunotherapy is currently discouraged after liver transplantation, given the high risk of graft rejection and death. The increasing complexity of HCC management and increased consideration of (neo)adjuvant strategies highlight the critical role of multidisciplinary care when making these decisions.

Case Report ‘Layer of Hope’: Managing Large Surface Wounds on Frontal Bare Bone in a Challenging Patient

This was a case of an elderly gentleman with large bleeding basal cell carcinoma occupying almost three quarter of the forehead managed with adjunct usage of integra acellular dermal regeneration template after lesion’s wide local excision despite challenged with patient’s newly diagnosed bicytopenia to rule out haematological malignancy. Standard management of tissue reconstruction with purely living tissue (split skin grafting) has higher risk of graft rejection due to bare bone as wound bed. This limits the neo-graft ability to achieve optimal potential of imbibition and inosculation. Thus, dermal matrix usage makes split skin grafting difficult wound bed has higher chance of surviving and hence shortens healing time and reduces hospital stay.

Anti-Angiogenic and Anti-Scarring Dual Effect of Galectin-3 Inhibition in Mouse Models of Corneal Wound Healing

Corneal scarring is the third leading cause of global blindness. Neovascularization of ocular tissues is a major predisposing factor for scar development. Although corneal transplantation is effective at restoring vision, some patients are at high risk of graft rejection due to the presence of blood vessels in the injured cornea. Current treatment options to control corneal scarring are limited and their outcomes are typically poor. In this study, using mouse models of corneal wound healing, we demonstrate that topical application of a small molecule inhibitor of galectin-3, GB1265: reduces (i) corneal angiogenesis, (ii) corneal fibrosis, (iii) infiltration of immune cells and (iv) expression of proinflammatory cytokine, IL-1β, in injured corneas. Four independent techniques (RNA-seq, NanoString, RT-qPCR, and Western blot analyses) all demonstrated that decrease in corneal opacity in the galectin-3 inhibitor-treated corneas is associated with a decrease in a number of genes and signaling pathways that are known to promote fibrosis. These findings allow us to place a high level of confidence in our conclusion that galectin-3 inhibition by a small molecule inhibitor, GB1265, has dual anti-angiogenic and anti-scarring effect. Targeting galectin-3 by GB1265, is thus, an attractive strategy for development of innovative treatment of myriad of ocular and nonocular diseases characterized by pathological angiogenesis and fibrosis.

The Tacrolimus Concentration/Dose Ratio Does Not Predict Early Complications After Kidney Transplantation.

Early-on post kidney transplantation, there is a high risk of graft rejection and opportunistic viral infections. A low tacrolimus concentration/dose (C/D) ratio as a surrogate marker of fast tacrolimus metabolism has been established for risk stratification 3months post-transplantation (M3). However, many adverse events occurring earlier might be missed, and stratification at 1month post-transplantation (M1) has not been investigated. We retrospectively analyzed case data from 589 patients who had undergone kidney transplantation between 2011 and 2021at three German transplant centers. Tacrolimus metabolism was estimated by use of the C/D ratio at M1, M3, M6, and M12. C/D ratios increased substantially during the year, particularly between M1 and M3. Many viral infections and most graft rejections occurred before M3. Neither at M1 nor at M3 was a low C/D ratio associated with susceptibility to BKV viremia or BKV nephritis. A low C/D ratio at M1 could not predict acute graft rejections or impaired kidney function, whereas at M3 it was significantly associated with subsequent rejections and impairment of kidney function. In summary, most rejections occur before M3, but a low C/D ratio at M1 does not identify patients at risk, limiting the predictive utility of this stratification approach.

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes.

Antithymocyte globulins (ATG) are T cell-depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with a high risk of graft rejection. Previously described effects besides the depletion of T cells have suggested additional modes of action and identified further cellular targets. We examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG at the single-cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Analysis of the paracrine factors present in the plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines, including interferon-γ (IFN-γ). Furthermore, we identified an increase in the surface expression of the programmed death ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we showed that this induction is dependent on the activation of JAK/STAT signaling via the binding of IFN-γ to interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrated that the modulation of the immune regulatory axis of programmed cell death protein 1 (PD1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including the proliferation and granzyme B release of activated T cells. Together, our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects.

Pilot longitudinal kidney transplant transition program promotes peer connections and transition readiness.

Adolescents who have received a kidney transplant are at high risk of graft rejection and transplant-related comorbidities around the time of transition from pediatric to adult care. While there has been a progress in tracking transition readiness, further work is needed to prepare adolescents for healthcare transitions. We describe a longitudinal cohort-based transition curriculum designed to prepare kidney transplant recipients for adult transplant care. Adolescent kidney transplant recipients aged 17 and older participated in the pilot cohort of the 2-year transition curriculum. Session topics included communication with the healthcare team, insurance, job skills, reflective practice, reproductive health, medications, and adult clinic introduction. Surveys were given to obtain narrative feedback, assess participant self-management behavior, and track curriculum knowledge. Each participant attended an average of two sessions, with 18 out of 30 eligible adolescents participating in at least one session. After transitioning to a virtual platform, there was increased attendance of participants who live greater than 150 miles from the transplant center. Adolescents highlighted the value of the program's group structure to relate to and learn from other participants. The pilot transition program successfully provided adolescent kidney transplant recipients the opportunity to learn alongside their peers and gain interdisciplinary knowledge to prepare for healthcare transition. The program converted to a virtual platform during the COVID-19 pandemic, with increased accessibility for participants who live further from the transplant center. Group-based programming for adolescents should be enhanced to further prepare them for transitions to adult medicine.

Donor gender effect on graft function in adult Egyptian patients undergoing living donor liver transplantation: A single centre study

ABSTRACT Background The aim of this study was to evaluate the role of donor-to-recipient gender match in the setting of living donor liver transplant as a potential predictor of graft and recipient survivals. Methods In this retrospective, single-center study, the data of 342 adult primary liver transplants were analyzed. The donor and recipient’s characters, intraoperative data, and postoperative outcomes were recorded. Results The donor-recipient gender matched patients had significantly better graft survival outcomes than the gender mismatched ones. The 2-year graft survival probability was 95.7% in the matched group compared to 89.1% in the mismatched one (p = 0.026). A female donor-male recipient combination (87.3%) showed worse 2-years graft survival than a male-to-male transplant (94.8%), while it gave better graft survival than male to female (61.3%). The estimated relative risk of graft rejection was 5.91 times significantly higher in a male–female combination than in a male-to-male one (Hazard ratio = 5.91, 95% CI = 1.34–26.11). Conclusion This study suggests that donor-recipient gender mismatch is associated with poor liver graft survival outcomes, with higher risk of graft rejection in male-female transplants than in male-to-male ones. Though, further larger studies including multiple datasets are needed, with adjustments for various graft, donor, and recipient factors to reach solid evidence.

The obstetric implications of pulmonary hypertension and lung transplant.

Pulmonary hypertension (PH) is present when the mean pulmonary artery pressure is elevated to >20mmHg as determined by right heart catheterization. It is categorized into five groups according to the underlying causes. Its presence is considered a contraindication to pregnancy for which therapeutic termination is usually advised due to grave maternal prognosis and pregnancy outcome. Nevertheless, pregnancies in affected women are increasingly reported, about half of which were unplanned, and two-thirds resulted in live births without increased foetal anomalies, notwithstanding increased risks of preterm birth, low birth weight, pre-eclampsia, other obstetric complications, and medical comorbidities, when managed under a multidisciplinary team in specialized centres. Successful lung transplant, the ultimate treatment for PH and other progressive lung diseases, restores fertility, and pregnancy is increasingly encountered, but there is a higher risk of graft rejection and mortality, compared with recipients of other organs. Preconception assessment is vital in optimizing maternal and pregnancy outcomes.

Management and Treatment Outcomes of High-Risk Corneal Transplantations.

Corneal transplantation is the most effective treatment for corneal blindness. Standard planned keratoplasties have a high success rate. Conditions such as active inflammation at the time of surgery, the presence of ocular surface disease, previous graft disease, or neovascularization make them more susceptible to rejection. These are so-called high-risk corneal transplantations. In our study, we selected 52 patients with a higher risk of graft rejection. A total of 78 procedures were performed. The main indications for the first keratoplasty were infections (59.6%) and traumas (21.2%). Visual acuity (VA) significantly improved from 2.05 logMAR on the day of keratoplasty to 1.66 logMAR in the latest examination (p = 0.003). An analysis of the graft survival showed a 1-year survival of 54% and a 5-year survival of 19.8% of grafts. The mean observation time without complications after the first, second, and third surgery was 23, 13, and 14 months, respectively. The best results were noted among patients with infectious indications for keratoplasty (p = 0.001). Among them, those with bacterial infection had the best visual outcomes (p = 0.047).

Posttransplant VEGFR1R2 Trap Eye Drops Inhibit Corneal (Lymph)angiogenesis and Improve Corneal Allograft Survival in Eyes at High Risk of Rejection.

PurposeTo assess whether topical application of VEGFR1R2 Trap after corneal transplantation can impair corneal (lymph)angiogenesis and promote murine corneal allograft survival in eyes at high risk of rejection.MethodsWe used the murine model of suture-induced neovascularization and subsequent keratoplasty in eyes at high risk of rejection, which is an established model for local drug application. After transplantation, the mice were treated with either VEGFR1R2 Trap (aflibercept) or human IgG Fc as eye drops for 2 weeks (three times/d). Deposition of VEGFR1R2 Trap in corneal tissue was detected by immunohistochemistry. Two and 8 weeks after transplantation, corneal (lymph)angiogenesis was assessed morphometrically. Dendritic cells (DCs) and regulatory T cells (Tregs) in the draining lymph nodes (dLNs) were examined by flow cytometry. Allograft survival was determined by corneal graft opacity scores.ResultsTopically applied VEGFR1R2 Trap penetrated into corneal host and graft stroma after keratoplasty in eyes at high risk of rejection. Additional postsurgical corneal hemangiogenesis (P < 0.0001) and lymphangiogenesis (P < 0.01) as well as infiltrating CD45+ leukocytes (P < 0.001) and macrophages (P < 0.01) were significantly reduced in the VEGFR1R2 Trap group compared to controls. VEGFR1R2 Trap eye drops significantly decreased the frequency of total CD11c+ DCs (P < 0.01), as well as activated CD11c+MHC II+ DCs (P < 0.01) and CD11c+CD40+ DCs (P < 0.05). In contrast, the frequency of CD200R+ regulatory DCs (P < 0.05) and Tregs in dLNs (P < 0.01) was enhanced. Moreover, long-term allograft survival was also improved (P < 0.05).ConclusionsTemporary, topical application of VEGFR1R2 Trap after corneal transplantation can achieve sufficient anti-VEGF activity, inhibit additional (lymph)angiogenesis, and significantly improve corneal allograft survival in eyes at high risk of rejection.Translational RelevanceVEGFR1R2 Trap eye drops after transplantation present a new therapeutic option for patients undergoing corneal transplantation and are at high risk of graft rejection.

Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score for Prediction of Pancreas Transplant Outcomes

The Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score were designed to assist in the evaluation of pancreases for transplant. Preprocurement Pancreas Suitability Score <17 and PancreasDonor Risk Index ≤1.57 were deemed ideal.We aimed to determine the ability ofthese scores to predict pancreas transplant outcomes. The Pancreas Donor Risk Index and the Preprocurement Pancreas Suitability Score were retrospectively calculated from a prospectively maintained database of consecutive pancreas transplants performed during a 13-year period (December 2004 to November 2017). Outcomes measuredwere rejection rate, graft and patient survival, and duration of hospital stay. Of 159 pancreas transplants (108 simultaneous pancreas and kidney transplants, 33 pancreas after kidney transplants, 18 pancreas-only transplants), full data were available for 155 (97%) to calculate Pancreas Donor Risk Indexes and 129 (81%) to calculate Preprocurement Pancreas Suitability Scores. Fortyseven patients (30%) experienced at least 1 episode of acute rejection. We calculated Pancreas Donor Risk Indexes for 155 patients, and 19 (23%) and 27 (38%) were in the ≤1.57 and >1.57 groups, respectively (P = .047). We calculated Preprocurement Pancreas Suitability Scores for 129 patients, and 12 (21%) and 27 (32%) were in the <17 and ≥17 groups, respectively (P = .202). Donor age and recipientfemale sex were the main predictors forrejection (binary logistic regression, P < .05). One-year graft survival rates were 95% and 81% forthe ≤1.57 and >1.57 PancreasDonor Risk Index groups,respectively, and 95% and 80% forthe <17 and ≥17 Preprocurement Pancreas Suitability Score groups, respectively (not significant). Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score were not helpful to predict graft/patient survival in our population. A higher Pancreas Donor Risk Index was associated with higher risk of graft rejection. Further studies with larger cohorts are required.

The Combination of Anti-Thymocyte Globulin and Basiliximab for Haploidentical Hematopoietic Stem Cell Transplantation

Objectives: Identical hematopoietic stem cell transplantation (haplo-HSCT) is associated with a higher risk of graft rejection when compared to matched sibling donor transplantations. Methods: The study included 34 patients who were treated with a novel regimen combining basiliximab, Anti-thymocyte globulin (ATG) and conventional immunosuppressive in the recipients of haplo-HSCT. Results: The cumulative incidence of grade II–IV and grade III–IV aGVHD was 38.2% and 11.8%, while the rates of limited and extensive cGVHD were 17.6% and 23.5%, respectively. Laboratory evidence of CMV and EBV reactivation were found in 9 patients (26.5%) and 6 patients (18.8%), respectively. The relapse rate of haplo-HSCT was 14.7% at 1 year; and 1-year OS and DFS were achieved in 58.8% and 55.9% of the patients, respectively. Conclusions: The results suggested that basiliximab combined with low-dose ATG could be a promising treatment strategy in haplo-HSCT.

Chronic kidney disease in children

Chronic kidney disease (CKD) is a major public health issue globally. Although not so common in children, its impact can be devastating with long-term consequences. Syndromal association, congenital abnormalities of the kidney and urinary tract, and other congenital anomalies usually present in childhood and have more impact in this population. Issues such as growth retardation, hormonal imbalance, psychosocial development, and transitions to adult care are specific to children and need to be addressed appropriately. With CKD, their nutritional requirement is quite different from adults and needs more careful planning and dietary modification to avoid growth retardation in these patients. Pharmacokinetics and pharmacodynamics of many drugs including immunosuppressants also differ from adults and need special considerations. Kidney transplantation is the best treatment modality available for end-stage renal disease (ESRD). Preemptive kidney transplantation is preferred to prevent growth retardation and psychosocial maladaptations in children with ESRD. Because lymphoid system development is on peak in adolescents and developing children, they are at high risk of graft rejection. Poor adherence to medication and recurrence of primary disease also affects long-term prognosis in adolescents adversely.

Comparison of Bone Marrow Versus Peripheral Blood in Haploidentical Transplantation Using Post-Transplant Cyclophosphamide- a Retrospective Analysis

Comparison of Bone Marrow Versus Peripheral Blood in Haploidentical Transplantation Using Post-Transplant Cyclophosphamide- a Retrospective Analysis

The significance of angiotensin II type 1 receptor (AT1 receptor) in renal transplant injury.

Humoral response beyond human leukocyte antigen (HLA) is of great interest in the transplant community. We decided to summarize the data on a new antigenic target called angiotensin II type 1 receptor (AT1 receptor). Non-HLA antibodies can now be detected in routine clinical care of patients after transplantation, but their role is not fully understood. Numerous analyses showed that non-HLA response may exert a higher risk of allograft rejection and allograft loss independently of the HLA system. Non-HLA response may even have a higher rate of antibody-mediated rejection. Information regarding antigen target, as well as the pathophysiology of its antibodies and diagnostic tools, is essential for a better understanding of non-HLA humoral response. Angiotensin II type 1 receptors are the most recognized target for non-HLA antibodies. Anti-AT1R Abs (anti-angiotensin II type 1-receptor-activating antibodies) may identify renal transplant patients at higher risk of graft rejection and loss. The presence of AT1 receptor expression analyzed together with anti-AT1R Abs should be considered for better transplant immunological risk assessment. Further assessment is required for a better understanding and to create appropriate therapeutic strategies.

Use of Ipilimumab and Pembrolizumab in Metastatic Melanoma in a Combined Heart and Kidney Transplant Recipient: A Case Report

New therapeutic agents such as checkpoint inhibitors are promising strategies in the treatment of metastatic melanoma. Transplant recipients are generally at higher risk of malign diseases. Limited data are available for the use and safety of these agents in this population. We describe a patient who had a stable transplant function over years after a combined heart and kidney transplantation. Immunosuppressive medications included tacrolimus and azathioprine and were later switched to sirolimus and azathioprine. Metastatic melanoma was diagnosed; after detailed explanation of the potential risk, the patient was initially treated with the anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab but experienced an acute kidney graft rejection and rapid progression. Rejection therapy with high-dose corticosteroids was successful, and kidney function was stabilized. Because of the urgent request of the patient for additional therapy, he received a PD-1 inhibitor. Acute kidney graft rejection resulted, with indication for acute dialysis. He developed severe candida pneumonia and died despite extensive antimicrobial therapy. Checkpoint inhibitors have become the standard in a broad entity of tumors. Organ transplant patients are at higher risk of developing malignant diseases. Limited data are available for the use of checkpoint inhibitors in this subgroup, and the use of checkpoint inhibitors is associated with a high risk of graft rejection.

TLI in pediatric patients.

Hematopoietic progenitor cell transplantation (HSCT) is a procedure used in different hematological diseases as part of the curative treatment, so the investigators propose a system of conditioning of reduced intensity based on total lymphoid irradiation (TLI) as an alternative to the classic total body irradiation (TBI) followed by haploidentical transplantation in patients compatible with a single HLA haplotype, as an alternative to patients who do not have an HLA compatible donor. A cohort of 25 patients with hematological disease underwent haploidentical HSCT from February 2015 to May 2018, conditioned with TLI from day -10 (2-4days of treatment) followed by thiotepa (5mg/kg/12h) and melphalan (70mg/m2/day) prior to HSCT and prophylaxis with ciclosporin (1.5mg/kg/12h). 2Gy/fraction was administered to complete 8Gy with IMRT and VMAT technique. 12% rejection of the transplant was obtained with acute GVHD < II (48%) and chronic GVHD 12%. No acute toxicity was recorded in irradiated patients and 56% survival of patients at the end of follow-up. Conditioning the haploidentical transplant with TLI, IMRT, and VMAT techniques compared with TBI and RT3D-C techniques is a feasible technique that helps inducing the necessary immunosuppression in patients with a high risk of graft rejection, minimal adverse effects, low incidence of GVHD, and high survival rate.

Higher Incidence of Graft Rejection in Non-Sibling Fully Matched Related Donor Stem Cell Transplants for Thalassemia Major: A Cautionary Note

▪Only 25-30% of patients with Thalassemia major (TM) will have a suitable HLA-matched sibling donor for an allogeneic SCT. In the absence of a HLA-matched sibling, an extended donor search within the family may yield a suitable donor, especially in societies with a high prevalence of consanguinity. We have previously reported inferior outcomes in patients who had a transplant from a non-sibling family donor. One of the criticisms of this was the issue of low resolution typing, which may have adversely impacted outcomes in some patients. We interrogated this data further to assess whether the poorer outcomes held up to scrutiny with the availability of high resolution HLA typing. Towards this we undertook a retrospective case-control study, adjusting controls for age and Lucarelli risk group (common confounders for clinical outcomes post-transplant in TM) with a 4:1 ratio of controls to cases.All consecutive patients with TM who had a stem cell transplant between the time periods 2007-2017, were included in this retrospective analysis. A total of 371 transplants were done with 281 matched sibling donor, 58 related donors (32 fully matched and 26 with 1-2 antigen mismatch), and 32 MUD donors (24 fully matched (10/10) and 8 with 1-antigen mismatch (9/10)).Subsequent to 2012, high resolution typing was done for all non-sibling related family donors. Of the 58 related donors, high resolution typing was available in 45, with twenty four 10/10 donors, nineteen 9/10 donors and two 8/10 donors. Further analysis was done in this sub-group (excluding the 8/10 donors), with rejection and death being considered as events. A control group from the fully matched sibling donor cohort was generated randomly after adjusting for age and Lucarelli Class.All patients received a myeloablative conditioning regimen (Busulphan/Treosulfan based). In-vivo T-cell depletion was done in 11 (45.8%) of matched related transplants and 54 (56.2%) of matched sibling donor transplants (P=0.359). A PBSC graft was used in 16 (66.7%) of matched related donor transplants compared with 36 (27.5%) of matched sibling donor transplants (P=0.012). There was no difference in the median CD34 cell dose achieved in both groups (Table 1). Table 1 shows baseline characteristics, transplant details and outcomes in the 10/10 matched related donors and fully matched sibling donor groups. Table 2 shows univariate and multivariate analysis for risk factors adversely affecting Thalassemia-free survival (TFS) using Cox regression analysis. The 2-year TFS in the 10/10 matched related donor group, 9/10 matched related donor group and fully matched sibling donor group was 56.8%±10.5%, 56.1%±11.9% and 81.8%±4% respectively (P=0.011) (Figure 1A). The 2-year overall survival (OS) in the 10/10 matched related donor group and 9/10 matched related donor group and the fully matched sibling donor group was 75.4%±9.9%, 64.5%±12.1% and 85.0%±3.7% respectively (P=0.168) (Figure 1B).This data on allogeneic transplants confirms our previous observations that there is a higher risk of graft rejection when the donor is a non-sibling related donor, even if fully matched on high-resolution typing (OR 4.8 ; 95% CI=1.3-18.2 : P=0.02). Transplant physicians must be aware this increased risk and counsel families appropriately. Further modifications in conditioning regimens and GVHD prophylaxis could potentially help in improving these outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Burden of cytomegalovirus disease in allogeneic hematopoietic cell transplant recipients: a national, matched cohort study in an inpatient setting

Purpose of the studyNo studies have compared the risk of mortality or graft-versus-host disease, in an inpatient setting in France, in allogeneic hematopoietic cell transplant recipients who develop cytomegalovirus disease with those who do not. This study assessed the impact of cytomegalovirus disease on clinical outcomes and healthcare resource utilization in allogeneic hematopoietic cell transplant recipients using the French Programme de Médicalisation des Systèmes d'Information database. Patients and methodsRecipients who had undergone allogeneic hematopoietic cell transplant in French hospitals between 2008 and 2011 were included in this retrospective, matched cohort study. Those with cytomegalovirus disease were each matched with two allogeneic hematopoietic cell transplant recipients without cytomegalovirus disease according to demographic and clinical characteristics. Probabilities of in-hospital mortality, graft rejection and/or graft-versus-host disease, and healthcare resource utilization were compared up to 12 months after cytomegalovirus disease diagnosis. ResultsOverall, 4884 transplant recipients were enrolled, of which 194 had cytomegalovirus disease. Of these, 165 recipients with cytomegalovirus disease were matched to 330 without cytomegalovirus disease (1:2 ratio). The development of cytomegalovirus disease was associated with a significantly higher risk of in-hospital mortality (relative risk = 1.7, p = 0.0005) and higher cumulative number of inpatient days (p < 0.0001), but was not associated with a significantly higher risk of graft rejection and/or graft-versus-host disease or healthcare costs. ConclusionsDue to the increased risk of in-hospital mortality and higher cumulative number of inpatient days in allogeneic hematopoietic cell transplant recipients with cytomegalovirus disease versus those without, new strategies to prevent and manage cytomegalovirus disease are warranted.