1-year Post-transplantation Research Articles

Long-Term Outcomes in Heart and Lung Transplants from HCV-Viremic Donors to Uninfected Recipients: The Donate HCV Trial

Purpose An early 6-month analysis of the DONATE HCV Trial demonstrated that hearts and lungs can be safely transplanted from HCV-infected donors using a shortened, 4-week, pre-emptive course of direct acting antivirals (DAA). Whether early findings are sustained in the longer-term remain an important area of investigation. Methods DONATE HCV is a single-center trial to transplant thoracic organs from HCV viremic donors, irrespective of HCV genotype, to HCV-uninfected adults. Sofosbuvir/velpatasvir, a pan-genotypic DAA, was administered for 4 weeks, beginning within hours of transplant. The primary composite outcome of HCV clearance and graft survival at 6 months post-transplant are now extended to the longer-term at 1- and 3-years. We also report on grade 3 or higher adverse events (AEs). (NCT03086044) Results Between March 2017 and December 2019, 65 participants were enrolled: 53 received lung and 12 received heart transplants. The median donor HCV viral load (VL) was 742,000 IU/mL (IQR 127,000 - 4.69 million). 56 of 65 (86%) recipients had detectable HCV VL immediately after transplant, with median VL of 2,000 IU/mL (IQR 800 - 9,000). HCV VL became negative by 2 weeks and subsequently remained undetectable in all participants. 63 of 65 (97%), 60 of 63 (95%), 46 of 51 (90%), and 19 of 24 (79%) participants were alive with excellent graft function and an undetectable HCV VL at 6 months, 1-year, 2-years, and 3-years post-transplant, respectively. 22 of 65 (34%) and 28 of 63 (44%) had acute cellular rejection requiring treatment at 6 months and 1-year post-transplant, respectively. 3 of 65 (5%) and 3 of 63 (5%) had antibody mediated rejection at 6 months and 1-year post transplant, respectively. No treatment-related AEs were identified. Outcomes between transplant recipients from HCV donors vs. non-HCV donors were similar, including the occurrence of renal failure, respiratory failure, and non-HCV infections. Conclusion These data demonstrate that recipients of thoracic organs transplanted from HCV viremic donors who receive a shortened antiviral treatment course initiated within hours of transplant, have excellent longer-term graft and recipient survival with similar AE profiles compared to transplant recipients who received thoracic organs from non-HCV donors.

Baseline Gas Transfer (KCO) and Accessible Alveolar Volume (VA) after Lung Transplant: Determinants and Relative Contributions on Graft Survival

<h3>Purpose</h3> Low baseline diffusing capacity (DLCO), at 1-year after lung transplant, is associated with an increased risk of graft loss. DLCO is the product of 2 measurements; the gas transfer factor (KCO) and the accessible alveolar volume (V_A). Our aim was to understand the relative contributions of baseline KCO and V_A on survival after lung transplant. <h3>Methods</h3> A retrospective cohort analysis was conducted of all bilateral lung transplant recipients between 1998 and 2018, with DLCO measured at 1 year after transplant. Low baseline V_A was defined as < Median %-pred, low baseline KCO as < Median %-pred for lung volume, and low FEV₁ as failure to achieve >80%-pred. Patients were divided into 4 groups: Normal V_A-Normal KCO, Normal V_A-Low KCO, Low V_A-Normal KCO, Low V_A-Low KCO. Multivariate logistic regression and Cox proportional hazard models were used for statistical analysis. <h3>Results</h3> 708 patients underwent double lung transplant during the study period. 258 patients had DLCO measured at 1-year post transplant. The mean recipient age was 44.0 (SD 15.5) with 50% males. The median time to measurement of DLCO was 378 days. The median (IQR) V_A %-pred was 82 (21), %-Pred KCO 74 (19) and %-Pred FEV₁ 84 (29). Donor age was significantly associated with low KCO OR 1.06 (95%CI 1.03-1.08), p<0.01. ILD and transplant era were significantly associated with low V_A, p<0.01. Multivariate analysis demonstrated that Low V_A-Normal KCO (HR 2.09 p=0.04) and Low V_A-Low KCO (HR 2.60 p<0.01) were independently associated with reduced survival after adjustment for native lung disease and low baseline FEV₁. There was a significant difference in the Kaplan-Meier curves for the 4 V_A-KCO groups, p<0.01 <b>Figure 1</b>. <h3>Conclusion</h3> Donor age, ILD and transplant era were associated with baseline KCO and VA. Low baseline V_A was a greater risk for future graft loss than low KCO. There may be benefit in the incorporation of baseline V_A and KCO at 1-year post transplant to identify patients with an increased risk of graft loss.

Outcomes of Mechanical Circulatory Support in Infants with Congenital Heart Disease Listed for Heart Transplant

<h3>Purpose</h3> Infants with congenital heart disease (CHD) and advanced heart failure are a growing population. We hypothesize that survival to transplant was superior in those infants supported with no MCS compared to those with ventricular assist device (VAD) or extracorporeal membrane oxygenation (ECMO). <h3>Methods</h3> This retrospective cohort study evaluates data from the 1987-2018 United Network for Organ Sharing (UNOS) database assessing patients <1yo with CHD who were listed for orthotopic heart transplant (OHT). Patients were divided into 3 categories at the time of listing and at time of transplant: No MCS, ECMO and VAD. The primary outcome was survival to transplant, while the secondary outcome was 1-year post-transplant survival. <h3>Results</h3> Analysis included 2755 patients of whom 62% (1705) survived to transplant and 50% (1378) survived from listing to 1-year post transplant. At the time of listing, 86% (2357) were not on MCS, 13% (360) were on ECMO, and 1% (38) on VAD. Average weight at the time of listing was 4.2±2.0 kg, with VAD patients larger (5.1±2.1 kg) than ECMO (4.0±1.5 kg) or no MCS (4.2±2.0 kg) (<i>p=0.003)</i>. At the time of listing, 53% of VAD patients, 62% of ECMO patients and 45% of patients without MCS were on inotropic support. In comparison to those patients not on MCS, death prior to transplant was highest for those patients on ECMO at listing, (HR 4.1, 95% CI 3.6-4.8) and equivocal if on VAD at listing (OR 1.6, 95% CI 1.0-2.5). 1-yr post-transplant mortality was higher if on ECMO at transplant (vs. no MCS, HR 4.0, 95% CI 3.0-5.3) but similar if on VAD at transplant (vs. no MCS, HR 1.4, 95% CI 0.8-2.5). <h3>Conclusion</h3> Infants with CHD listed for OHT have poor outcomes regardless of support modality, with less than 2/3 surviving to transplant and only half surviving to 1-year post-transplant. Patients supported with ECMO have particularly dismal survival, while VAD outcomes are similar to those not requiring MCS. Strategies to effectively improve survival in this high-risk cohort are urgently needed.

Secondary esophageal squamous cell carcinoma after hematopoietic stem cell transplantation.

We evaluated cases of esophageal squamous cell carcinoma (ESCC) that developed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our institution. Allo-HSCT was performed in 1534 patients (1776 cases) at our institution from 2001 to 2016. Overall, 602 patients were confirmed to have survived for 2 or more years and 154 underwent upper gastrointestinal endoscopy at least 1-year post-transplantation. ESCC was discovered in 17 patients (1.1%), 15 of whom had 31 lesions discovered at our institution (ESCC group). A retrospective comparative study was conducted with the remaining 137 patients for whom no ESCC was noted (non-ESCC group), and we also evaluated the clinicopathological characteristics of the ESCC group. History of TBI (total body irradiation) and bone marrow transplant was significantly higher in the ESCC group. The mean time from transplantation to detection of ESCC was 82.3months. Localization was upper thoracic in 12 cases, middle thoracic in 10, cervical in 4, lower thoracic in 3, and upper to lower thoracic in 2. Treatment comprised endoscopic submucosal dissection in 23 cases, surgery in 4, untreated due to worsening primary disease in 3, and chemoradiotherapy in 1. In this study, lesions were located in the cervical to upper thoracic esophagus in approximately 60% of all secondary ESCC cases after allo-HSCT. History of TBI and bone marrow transplantation are high risk of ESCC, and proactive screening endoscopy is desirable.

Functional B Cell Reconstitution Following Allogeneic Stem Cell Transplantation

Immune reconstitution is critical to long term survivability in recipients of allogeneic hematopoietic cell transplantation (HCT), mitigating both relapse as well as infection risk. However, both graft versus host disease (GVHD) and post HCT immunosuppression used to prevent it impair immune recovery, particularly functional B cell reconstitution which may not happen for several months post-transplant. This is relevant for post-transplant vaccination which in some centers is delayed till immune cell recovery. In this retrospective, Virginia Commonwealth University institutional review board (IRB) approved study, T helper and B cell recovery for up to two years following HCT was evaluated in 212 patients transplanted between 2015 and 2019. There were 69 HLA matched related &amp; 143 unrelated donor transplant recipients. Median age of the patients was 56 years (range 19-74); conditioning regimens utilized were reduced intensity (RIC) in ~62% of the patients and rabbit anti-thymocyte globulin was used in ~72% of the patients. Blood stem cells were given in 183 patients and bone marrow in 29. Only patients with hematological malignancies were included in this study. Landmark analysis was carried out, with patients who did not survive the first 6 months post-transplant excluded. Of these patients, 85% are surviving. Median CD3+/4+ (Th) cell counts were 153 at 6 months, 228 at 1-year, 296 at 2 years, and corresponding B cell counts were 70, 175, &amp; 273. Plotting Th and B cell counts over time in each individual donor-recipient pair demonstrated close correspondence between Th and B cell recovery, with synchronous recovery observed in most patients, median R 0.76 (range: 0.01-0.99). The slope of the B/Th cell curves for each patient then were compared in a subset of patients, and demonstrated a significant difference between those patients who either did not develop GVHD or only had acute GVHD as opposed to those who developed both acute and chronic GVHD (1.3±1.4 B cells/Th cells and 1.1±1.2 vs. 0.5±1, P=0.02 and 0.06 respectively), suggesting poor B cell recovery in those with chronic GVHD. Different immune recovery kinetics were observed amongst patients (Figure 1); A) rapid B cell recovery, highest absolute B cell count between 30 and 180 days post-HCT, B) intermediate B cell recovery, days 180 and 455, C) delayed B cell recovery, days 455 and 725 days, and D) minimal to no B cell recovery. A higher relative risk for developing acute + chronic GVHD was seen in the intermediate B cell recovery group when compared to those with delayed recovery, RR = 2.38 (95% CI 1.08-5.25). Functional B cell studies were performed in a subset, by measuring IgG levels and anti-pneumococcal antibody titers. Correlation was observed between Th cell count and IgG levels over time in individual patients (median R = 0.57). Pneumococcal titers were also measured at approximately 6 months, 1- and 2-years post-transplant as patients were given a series of PCV13 &amp; PSV23 vaccinations 6 months after HCT. When the antibody titers against unique pneumococcal serotypes were analyzed in individual patients, these varied within each individual, following a declining trend in levels for antibodies against different serotypes; this decline occurred on a logarithmic scale suggesting differential immunogenicity of the pneumococcal antigens, and also mathematically ordered, rather than random Th and B cell responses (Figure 2A). When the serotypes with the highest titers in most patients were correlated with Th and B cell counts measured simultaneously, no association was observed. Further, when fold increase in pneumococcal titers beyond 1-year post transplant were compared across different groups of patients based on their GVHD status, no significant difference was observed in their antibody responses (Figure 2B). In conclusion, our data suggest synchronous Th and B cell reconstitution post allogeneic HCT, both in numeric and functional terms, and thus strategies to help promote T cell recovery, such as IL-7 administration post-transplant, are necessary to encourage optimal immune reconstitution. Vaccine responses beyond 6 months, as in the institutional practice reported here, are independent of GVHD status and numeric immune cellular recovery. These findings are consistent with the notion that immune recovery is a dynamical, rather than a stochastic process. Disclosures No relevant conflicts of interest to declare.

1 -YEAR PROTOCOL BIOPSIES IN PEDIATRIC KIDNEY TRANSPLANT CHILDREN: ARE UNFAVORABLE HISTOLOGICAL LESIONS RELATED TO NO ADHERENCE?

Introduction: In adult recipients histological findings in surveillance biopsies at 1-year post kidney transplantation (KT) correlate independently with short and long-term graft survival. Donor specific antibodies (dnDSA) are associated with antibody- mediated rejection. Non-adherence (NOA) to treatment, is a risk factor for dnDSA. Studies in children with KT with protocol biopsies are scarce. Objective: To evaluate the prevalence of favorable (FAV) and unfavorable (UNFAV) histological lesions (FAV) for graft survival in 1-year protocol biopsies of KT children and to identify risk variables for these lesions. Methods: Prospective cohort study in all recipients of a 1st KT between 06/01/2018 and 05/30/2019. (TABLE 1) According to their histological risk, lesions were grouped in “FAV” and “UNFAV”. “FAV” lesions were: 1) minor morphological changes, with absence of inflammation and / or fibrosis and / or chronic glomerulopathy or glomerulonephritis, 2) Acute Interstitial inflammation without interstitial fibrosis or glomerular changes 3) Mild Interstitial fibrosis with absence of interstitial inflammation. “UNFAV” lesions were: 1) moderate-severe interstitial fibrosis without inflammation 2) acute or chronic active rejection mediated by antibodies or T cells 3) de novo glomerular disease 4) polyoma virus-associated nephropathy. dn-DSA were sought simultaneously with kidney biopsy. TAC and / or SRL variation coefficient (VC) >25% was considered a surrogate of NOA. Results: 38 children were included. 29 had “FAV” lesions (76%): 23, Minimal morphological changes, and 6 mild fibrosis. Nine had “UNFAV” histology (24%): One had disease recurrence, three acute vascular rejection, (2/3 subclinical rejection; 1/3 DSA+) and four had moderate fibrosis (2 had graft hydronephrosis and 2 had previous AR,1DSA+). Mean eGFR in patients with “UNFAV” lesions was 39 ± 12.1 ml / min/ 1.73m2 vs 65.3 ± 18 ml / min / 1.73m2 in those with “FAV” (p=0.0003). Both groups had similar pre KT clinical and demographic characteristics. (TABLE2). UNFAV patients had higher incidence of previous Acute Rejection (TABLE2). TAC or SRL VC was: < 25% in 71% of patients (n= 27), and > 25% in 19% of patients (n=11), those with irregular intake. Children with VC> 25% had higher risk of an “UNFAV” lesion in protocol biopsy (OR: 4.8; p=0,04) and higher prevalence of dnDSA (18% vs 0%; p=0.02) Conclusion: In this cohort, FAV lesions were the most prevalent and were associated with negative dnDSA and TAC or SRL VC <25%. Children with UNFAV lesions had lower eGFR. Those with TAC or SRL VC>25% had higher risk of an “UNFAV” lesion, and higher prevalence of dnDSA. Follow-up of this cohort is imperative.

Orthotopic Heart Transplantation in the Diabetic Patient, are We Still Worried? A Review of 952 Consecutive Patients

Diabetes is common in heart failure patients and almost a quarter of heart transplant (HTx) recipients are diabetic at 1-year post transplant. The effect of diabetes on transplant outcomes is conflicting. The goal of this study was to examine the impact of diabetes on post-transplant outcomes at a large single center. We divided 952 patients at our center transplanted from 2010 to 2018 into those with (n = 274) and without pre-transplant diabetes (n = 578). The diabetic patients were further divided: tight glucose control (HbA1c <5.9. n= 17) and relaxed glucose control (HbA1c >7.0; n = 23) Demographic data and outcomes were compared between groups. There was no significant difference between groups in 1-year survival, freedom from cardiac allograft vasculopathy, non-fatal major cardiac events, rejection, new-onset dialysis, or infection. There was a trend towards worse 1-year survival in the relaxed glucose control group compared with the tight control group (82.6 v 94.1%; p=0.35). There was no difference in other outcomes between groups. While pre-transplant diabetes is often considered an important factor in selecting appropriate heart transplant candidates, this large single-center analysis does not demonstrate an association between pre-transplant diabetes and post-transplant outcomes, regardless of the adequacy of glucose control.

Post-transplant obesity impacts long-term survival after liver transplantation

BackgroundShort-term survival after orthotopic liver transplantation (OLT) has improved over the past decades, but long-term survival remains impaired. The effects of obesity on long-term survival after OLT are controversial. Because pre-transplant body mass index (BMI) can be confounded by ascites, we hypothesized that post-transplant BMI at 1 year could predict long-term survival. MethodsA post-hoc analysis was performed of an observational cohort study consisting of adult recipients of a first OLT between 1993 and 2010. Baseline BMI was measured at 1-year post-transplantation to represent a stable condition. Recipients were stratified into normal weight (BMI < 25 kg/m2), overweight (25 ≤ BMI ≤ 30 kg/m2), and obese (BMI > 30 kg/m2). Kaplan-Meier survival analyses were performed with log-rank testing, followed by multivariable Cox proportional hazards regression analysis. ResultsOut of 370 included recipients, 184 had normal weight, 136 were overweight, and 50 were obese at 1-year post-transplantation. After median follow-up for 12.3 years, 107 recipients had died, of whom 46 (25%) had normal weight, 39 (29%) were overweight, and 22 (44%) were obese (log-rank P = 0.020). Obese recipients had a significantly increased mortality risk compared to normal weight recipients (HR 2.00, 95% CI 1.08–3.68, P = 0.027). BMI was inversely associated with 15 years patient survival (HR 1.08, 95% CI 1.03–1.14, P = 0.001 per kg/m2), independent of age, gender, muscle mass, transplant characteristics, cardiovascular risk factors, kidney- and liver function. ConclusionObesity at 1-year post-transplantation conveys a 2-fold increased mortality risk, which may offer potential for interventional strategies (i.e. dietary advice, lifestyle modification, or bariatric surgery) to improve long-term survival after OLT.

Use of Nakanuma staging and cytokeratin7 staining for diagnosing recurrent primary biliary cholangitis after living-donor liver transplantation.

Diagnosis of primary biliary cholangitis (PBC), which recurs in approximately 30% of liver transplant recipients, is histology-based, but no staging system has been established for recurrent PBC (rPBC). We used the Nakanuma staging system and cytokeratin7 (CK7) staining to examine post-transplant liver biopsy specimens retrospectively and to evaluate histological features of rPBC. From 107 patients who underwent living donor liver transplantation for PBC, 60 recipients with 214 liver biopsies after 1-year post transplant were enrolled. Fibrosis, bile duct loss (BL), cholangitis activity, hepatitis activity, and CK7-positive hepatocytes were scored. Nakanuma staging was based on fibrosis and BL scores. We examined the correlation of scores and clinicolaboratory data among rPBC patients. We also evaluated whether chronological change of stage was correlated with liver-related failure. Of 214 biopsies, 52 were protocol biopsy; 162 were episodic. Higher BL, cholangitis activity, and hepatitis activity scores were associated with rPBC diagnosis. At median follow up of 10.0years (range 1.4-18.7years), 29 (48%) patients were diagnosed with rPBC at 4.6years (range 1.3-14.5years). Liver-related failure occurred in five rPBC cases; three from rPBC, and two from chronic rejection. At rPBC diagnosis, higher BL and CK7 scores were more frequent in patients who developed liver-related failure than in other patients (P = 0.04, P < 0.01, respectively). In failure patients, the Nakanuma stage increased over time, and reached up to stage4, whereas the Scheuer stage did not reach above stage3. Nakanuma staging is associated with rPBC and disease progression. Scores for BL and CK7 might be early markers for progressive rPBC.

Myocardial structural and functional changes in patients with liver cirrhosis awaiting liver transplantation: a comprehensive cardiovascular magnetic resonance and echocardiographic study

BackgroundCardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation.MethodsThis study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19).ResultsCMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: − 24.2 ± 2.7% in cirrhosis vs − 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from − 24.9 ± 2.4% to − 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001).ConclusionsMyocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

Impact of recipient functional status on 1-year liver transplant outcomes.

BACKGROUNDThe Karnofsky Performance Status (KPS) scale has been widely validated for clinical practice for over 60 years.AIMTo examine the extent to which poor pre-transplant functional status, assessed using the KPS scale, is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation.METHODSThis study included 38278 United States adults who underwent first, non-urgent, liver-only transplantation from 2005 to 2014 (Scientific Registry of Transplant Recipients). Functional impairment/disability was categorized as severe, moderate, or none/normal. Analyses were conducted using multivariable-adjusted Cox survival regression models.RESULTSThe median age was 56 years, 31% were women, median pre-transplant Model for End-Stage for Liver Disease score was 18. Functional impairment was present in 70%; one-quarter of the sample was severely disabled. After controlling for key recipient and donor factors, moderately and severely disabled patients had a 1-year mortality rate of 1.32 [confidence interval (CI): 1.21-1.44] and 1.73 (95%CI: 1.56-1.91) compared to patients with no impairment, respectively. Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13 (CI: 1.02-1.24) and 1.16 (CI: 1.02-1.31), respectively.CONCLUSIONPre-transplant functional status is a useful prognostic indicator for 1-year post-transplant patient and graft survival.

Reduced-Toxicity (BuFlu) Conditioning Is Better Tolerated but Has a Higher Second Transplantation Rate Compared to Myeloablative Conditioning (BuCy) in Children with Inherited Metabolic Disorders.

Hematopoietic stem cell transplantation (HCT) is a primary treatment for various inherited metabolic disorders (IMDs). Achieving stable and sustained engraftment while minimizing transplantation-related morbidity and mortality is critical to optimizing outcomes for IMDs. Traditional regimens have used myeloablative approaches, primarily busulfan and cyclophosphamide (BuCy), which is associated with significant regimen-related toxicity. Alternatively, reduced-toxicity regimens, such as busulfan and fludarabine (BuFlu), have been proposed to offer similar efficacy with reduced toxicities. We compared transplantation-related outcomes with BuCy-based and BuFlu-based conditioning in patients with IMDs. We retrospectively analyzed the University of Minnesota's transplantation database for patients with IMDs who underwent HCT using a BuCy (with alemtuzumab) or BuFlu (with antithymocyte globulin) preparative regimen between March 2008 and September 2017. Overall survival (OS), event-free survival (EFS), and incidence of neutrophil and platelet recovery were determined using standard definitions. Complications such as graft failure, sinusoidal obstruction syndrome, hemorrhagic cystitis, and respiratory failure were compared. Graft failure includes primary and secondary aplastic graft failure with and without autologous recovery. The incidence of viral infections post-transplantation in the 2 regimens was also determined. A total of 99 patients underwent HCT for IMDs during the study period. Sixty-four patients received BuCy conditioning, and the other 35 received BuFlu. Hurler syndrome (46%) and adrenoleukodystrophy (43%) were the most common IMDs, and umbilical cord blood was the most common graft source (74%). One-year OS was similar in the 2 groups (81.2% in BuCy versus 85.5% in BuFlu; P=.8), with an EFS of 75% versus 63%, respectively. The 2 groups also had similar incidences of grade III-IV acute GVHD (9% versus 6%; P=.5) and chronic GVHD (9% versus 7%; P=.67). Neutrophil and platelet recovery were similar in the 2 groups, with a significantly shorter duration of hospital stay noted in the BuFlu cohort (median, 21 days versus 34 days; P=.002). The cumulative incidence of graft failure was significantly higher in the BuFlu group (29% versus 14%; P=.08), as was the rate of second HCT (27% versus 3%; P=.001). The incidences of adenoviral infection (14% versus 0%; P=.02) and hemorrhagic cystitis (23% versus 3%; P=.01) were higher in the BuCy group. T cell engraftment occurred significantly sooner with BuCy conditioning until 1-year post-transplantation, but donor myeloid engraftment was similar in the 2 groups. Our data indicate that reduced-toxicity conditioning is associated with lower rates of infection and other transplantation-related complications but is concerning for a higher rate of graft failure in patients with IMDs. Alternate immunosuppressive agents and novel techniques should be considered to minimize toxicities and reduce complications.

Diet Quality of Long-Term Allogeneic and Autologous Stem Cell Transplant (HCT) Survivors

Introduction Long-term hematopoietic stem cell transplant (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population, yet no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), specifically designed to provide guidance for making healthy food choices. The aims of this study were to evaluate the extent to which HCT survivors adhere to the DGA and to determine nutrient intake adequacy. A secondary aim was to assess their willingness to take part in a future nutritional program or dietary intervention. Methods The study population included adults (≥18 y), who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1-year post-transplantation. Dietary intake was assessed using the Block 2014 food frequency questionnaire and diet quality (adherence to the DGA) was estimated using the Healthy Eating Index-2015 (HEI-2015). A HEI score of ≤50 indicates "poor diet quality", 51-80 suggests a "diet that needs improvement", and &gt;81 indicates "good diet quality" out of maximum of 100. HEI-2015 scores by patient and transplant characteristics were analyzed by ANCOVA. Nutrient intake adequacies of the group were estimated by determining the percentage of the group falling below the Estimated Average Requirement (EAR) of the Dietary Reference Intakes. Receptivity to participate in a dietary intervention to stay healthy was measured by the question, "How willing would you be to take part in a healthy nutrition program or diet intervention?" Response categories included, "not at all," "somewhat," and "definitely". Results Between December 2017 and September 2018, 124 survivors were invited to participate, of whom 90 (51 autologous and 39 allogeneic HCT survivors) completed the dietary intake assessment and were included in the analysis. Majority were male (56%), White (72%), married (81%) and completed some college education (57%). Most participants were overweight (34%) or obese (37%). The median time from the HCT was 5.2 years. Mean ±SE HEI-2015 scores were 61.6 ± 1.3 and 60.7 ± 2.2 for the 18-64 y and ≥65 y age groups, respectively, slightly higher than the US general population. Adherence to a good quality diet was reported by only 10% of survivors. The majority of the survivors reported a diet in need of improvement (82%) or a poor-quality diet (8%). Intakes of vitamin A (720 ± 447 mcg/d), vitamin C (82 ± 73 mg/d), vitamin D (4.4 ± 3.4 mcg/d), magnesium (253 ± 133 mg/d), and calcium (781 ± 430 mg/d) suggested inadequacy, as more than 50% of the group fell below the specific EARs. Sodium intake at 2834 ± 1345 mg/d exceeded the DGA recommendation of 2300 mg/d. Fiber intake at 8.9 g per 1000 kcal/d was significantly below the Adequate Intake of 14 g per 1000 kcal/d. "Change in taste" was the only variable associated with lower quality of diet (p=0.02). Interestingly, 29% of HCT survivors reported persistent altered taste sensation. No significant relationships were seen for participant's demographics and diet quality which may be due to a sample population skewed toward older, causations and socioeconomically advantaged individuals. More than two thirds of participants (73%) indicated an interest in participating in dietary intervention. HCT survivors within 2 years of transplant were more likely to be receptive to participation in a diet intervention study compared to survivors beyond 2 years (52% vs 28%, p=0.0013). Conclusion Adult HCT survivors report poor adherence to the 2015 Dietary Guidelines for Americans and have numerous short-fall nutrient intakes. However, the willingness to participate in a nutritional program or dietary intervention in this survivorship population was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care. Disclosures Wingard: Celgene: Consultancy; Merck: Consultancy; Shire: Consultancy; Ansun: Consultancy; Pluristem: Consultancy.

Cytomegalovirus in Allogeneic Hematopoietic Transplantation: Impact on Costs and Clinical Outcomes Using a Preemptive Strategy.

Cytomegalovirus (CMV) results in significant morbidity and mortality following hematopoietic cell transplantation (HCT). Establishing the cost and clinical impact is imperative to the selection of appropriate CMV preventative strategies. This is a retrospective cohort study of consecutive patients undergoing their first allogeneic HCT between January 1, 2009, and December 31, 2013. Detailed clinical and institutional cost data were obtained from the start of conditioning through 1-year post-transplantation. Baseline characteristics, resource utilization, costs, and outcomes were compared between patients with and without clinically significant CMV infection (csCMVi). One hundred seventy out of 388 patients (44%) developed csCMVi within 1 year after HCT. Within the first year post-HCT, patients with csCMVi had a significantly longer transplantation-related length of stay (mean, 91.7 days versus 78.3 days; P < .0001) and more frequent and prolonged hospitalizations (mean, 2.4 versus 1.7 admissions [P < .0001]; mean, 39.1 versus 31.5 inpatient days [P=.001]) without significantly more admissions to the intensive care unit (28.2% versus 21.6%; P=.408). The use of granulocyte colony-stimulating factor was greater in patients with csCMVi (73.5% versus 54.1%; P=.0001), although no significant differences were demonstrated in mean platelet or red blood cell (RBC) transfusions. Total costs were also higher in patients with csCMVi (mean cost difference, $45,811; 95% CI, $26,385 to $67,544). However, the incidence of graft-versus-host disease (GVHD) and selected infectious complications was not significantly different between the 2 groups. There were no significant differences in 1-year and 5-year post-transplantation overall survival (OS) or nonrelapse mortality (NRM) between those with and those without csCMVi, although relapse of underlying disease was significantly lower in the csCMVi group. Overall, our data show that allogeneic HCT recipients with csCMVi had significantly greater medical resource utilization and costs than those without csCMVi. However, clinical outcomes, including GVHD, infections, and mortality, were similar in the 2 groups. Further study is needed to determine the cost-effectiveness of CMV preventive modalities.

Predictors of return to work after kidney transplantation: a 12-month cohort of the Japan Academic Consortium of Kidney Transplantation study

ObjectivesTo investigate the cumulative return-to-work (RTW) rate and to identify predictors of employment after kidney transplantation (KT).DesignRetrospective, outpatient-based cohort study.SettingThis was a single-centre study of the largest Japanese kidney transplant...

Clinical outcomes of valganciclovir prophylaxis in high-risk (D+/R-) renal transplant recipients experiencing delayed graft function.

Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear. This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n=72) versus those with immediate graft function (IGF; n=66). Cytomegalovirus viremia by 12months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P=0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P=0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P=0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P=0.62) or patient survival (98.5% vs 95.8%, P=0.62) at 1 year between the IGF and DGF groups, respectively. Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.

Donor-Recipient Body Weight Mismatch May Affect Glomerular Basement Membrane Thinning in Electron Microscopic Examination of 1-Hour Renal Allograft Biopsy Specimens

BackgroundAlthough an association between body weight mismatch and impaired graft function has been reported, few histologic studies have evaluated this issue, especially using electric microscopic analysis. During routine observations, we have noted a thin glomerular basement membrane (GBM) in the 1-hour biopsy specimen in cases with an overweight recipient and a lightweight donor. Therefore, we hypothesized that donor-recipient body weight mismatch affects the GBM thickness in the 1-hour biopsy specimen. The aim of the present study was to clarify the effect of donor-recipient body weight mismatch on the GBM thickness of the 1-hour biopsy specimen measured using electron microscopy. MethodsWe used an electron microscope to measure the GBM thickness of specimens at 1-hour post-transplantation (n = 24) and at 1 year post-transplantation (n = 17). The GBM thickness of cases with donor-recipient body weight mismatch was compared with those without mismatch. In accordance with a previous study, we defined a donor/recipient body weight ratio of less than 0.9 as donor-recipient body weight mismatch and a ratio of more than 0.9 as no mismatch. ResultsAt 1-hour post-transplantation, the mean GBM was significantly thinner in the mismatch group than in the nonmismatch group. However, at 1-year post-transplantation, the mean GBM thickness did not significantly differ between the 2 groups. ConclusionsThe GBM thickness at 1-hour post-transplantation is thinner in cases with donor-recipient body weight mismatch than in cases without mismatch. This implies that donor-recipient body weight mismatch may have to be considered when assessing donor-derived thin GBM disease using the 1-hour biopsy specimen.

Developing DSA Post-Lung Transplant - Identifying Risk Factors

Purpose Donor specific antibodies (DSA) to mismatched human leukocyte antigens have been reported to adversely affect the outcomes of lung transplantation. This study aimed to identify the risk factors for the development of DSA within 1-year post-transplant and examine its impact on recipients’ medium-term survival. Methods Recipients’ age, type of transplantation (single lung or bilateral lungs), pre-existing antibodies, post-op DSA, method of transplantation (ECMO, off-pump or on-pump), primary graft failure (PGD) grade 3 at 72hrs, blood transfusion, post-op ITU stay, ECMO usage and renal support, and survival status were collected from the unit's database. Binary logistic regression was used to identify risk factors for the development of post-op DSA within 1-year post-transplant. Multivariable Cox regression was performed to identify risk factors for survival. Results From January 2012 to October 2017, 259 adult patients received lung transplantation in our unit and 242 (93.4%) survived beyond 30-day post-op. Recipients who died within 30-day post-transplant were not included, as the causes of their death were less likely to be influenced by or associated with post-op DSA. Among these 242 recipients, 46 (19.0%) had pre-existing antibodies and 129 (53.3%) had DSA detected within 1-year post-transplant. Among all the potential risk factors, transplantation performed with ECMO (p = 0.007, OR 3.06, 95% CI: 1.36-6.90) are significantly associated with post-op DSA within 1-year post-transplant. Age (p = 0.009, OR 1.03, 95% CI: 1.01-1.05), post-op renal support (p = 0.015, OR 2.23, 95% CI: 1.17-4.26), PGD grade 3 at 72hrs (p = 0.001, OR 2.79, 95% CI: 1.54-5.05), and red blood cell transfusion (p < 0.001, OR 1.17, 95% CI: 1.11-1.23) are associated with worse medium-term survival, but neither pre-existing antibodies (p = 0.454) or post-op DSA (p = 0.479) has an impact on survival. Conclusion Use of ECMO for lung transplantation is associated with DSA development within 1-year post-transplantation. However, the presence of DSA within 1-year post-transplant has no impact on medium-term survival in this cohort. Further study is required to look at the effect of DSA on the development of chronic lung allograft dysfunction and long-term survival. Donor specific antibodies (DSA) to mismatched human leukocyte antigens have been reported to adversely affect the outcomes of lung transplantation. This study aimed to identify the risk factors for the development of DSA within 1-year post-transplant and examine its impact on recipients’ medium-term survival. Recipients’ age, type of transplantation (single lung or bilateral lungs), pre-existing antibodies, post-op DSA, method of transplantation (ECMO, off-pump or on-pump), primary graft failure (PGD) grade 3 at 72hrs, blood transfusion, post-op ITU stay, ECMO usage and renal support, and survival status were collected from the unit's database. Binary logistic regression was used to identify risk factors for the development of post-op DSA within 1-year post-transplant. Multivariable Cox regression was performed to identify risk factors for survival. From January 2012 to October 2017, 259 adult patients received lung transplantation in our unit and 242 (93.4%) survived beyond 30-day post-op. Recipients who died within 30-day post-transplant were not included, as the causes of their death were less likely to be influenced by or associated with post-op DSA. Among these 242 recipients, 46 (19.0%) had pre-existing antibodies and 129 (53.3%) had DSA detected within 1-year post-transplant. Among all the potential risk factors, transplantation performed with ECMO (p = 0.007, OR 3.06, 95% CI: 1.36-6.90) are significantly associated with post-op DSA within 1-year post-transplant. Age (p = 0.009, OR 1.03, 95% CI: 1.01-1.05), post-op renal support (p = 0.015, OR 2.23, 95% CI: 1.17-4.26), PGD grade 3 at 72hrs (p = 0.001, OR 2.79, 95% CI: 1.54-5.05), and red blood cell transfusion (p < 0.001, OR 1.17, 95% CI: 1.11-1.23) are associated with worse medium-term survival, but neither pre-existing antibodies (p = 0.454) or post-op DSA (p = 0.479) has an impact on survival. Use of ECMO for lung transplantation is associated with DSA development within 1-year post-transplantation. However, the presence of DSA within 1-year post-transplant has no impact on medium-term survival in this cohort. Further study is required to look at the effect of DSA on the development of chronic lung allograft dysfunction and long-term survival.

The Incidence of Acute Kidney Injury Following Lung Transplantation Performed on Cardiopulmonary Bypass; Risk Factors, Effect on Short and Long-Term Mortality

Purpose Acute Kidney Injury (AKI) occurs in approximately 30% after cardiac surgery with cardiopulmonary bypass (CPB) and has negative effect on outcome. The incidence and outcome of AKI after lung transplantation (Ltx) with or without CPB is unclear. Definitions of AKI include RIFLE, AKIN and the most recent 2012 KDIGO criteria. The incidence and effects of AKI after Ltx has been reported inconsistently, using various definitions and often not including use of CPB. Therefore, we aimed to find the incidence, predictors and long-term effects of AKI early after Ltx with CPB. Methods We performed a retrospective cohort study of 186 consecutive Ltx patients at our institution from 2010 through 2015. CPB was used in all cases. The primary outcome was occurrence of AKI in the first 7 postoperative days, defined and staged according to creatinine criteria of the 2012 KDIGO system. Secondary outcomes included risk factors, use of CRRT and mortality. Results Of 177 Ltx recipients included, AKI occurred in 57 (32%), stratified into AKI 1 in 20% (n=36), and AKI 2&3 in 12% (n=21). CRRT was used in 8.5% during hospital stay. In multivariate analysis PAH as underlying diagnosis [OR 12.9 (1.4-123), p=0.026], and CPB time [per minute increase; OR 1.013 (1.003-1.023), p=0.008] were predictive for AKI. Mortality at 3 months was significantly higher in the AKI group compared to the No AKI group (11% vs 2%; p=0.02). At 1-year post transplant there was no significant difference in mortality between groups (18% vs 11%; p=0.22). Kaplan-Meier analysis showed no significant difference between No AKI vs Any AKI in long-term survival (fig.1). Conclusion By the KDIGO definition, AKI occurred in 32% of Ltx recipients with the routine use of CPB. This is similar to the incidence in cardiac surgery, and low compared to previous reports in Ltx recipients. Although short term survival was lower, the occurrence of AKI was not associated with impaired long-term overall survival.

Post-Transplant Trends in BNP Levels among Recipients of Heart versus Heart-Kidney Transplantation

Purpose Circulating levels of b-type natriuretic peptide (BNP) are elevated following heart transplantation (HT), peak at 1-2 months post-HT, and decline over the course of several months but rarely return to normal. We sought to determine the time course of BNP level following combined heart-kidney transplantation (HKT) compared to HT alone. Methods Between July, 2014 and August, 2017, 11 patients underwent HKT; they were matched based on age, gender, race and body mass index (BMI) to 22 patients undergoing isolated HT. Baseline demographics, serial BNP levels, and estimated glomerular filtration rate (eGFR; ml/min/1.73 m 2 ) were monitored in patients at post-transplant days 30, 60, 90, 180 and 365. Wilcoxon rank-sum test was used to compared median BNP levels at different time points between the groups. Results Average age of HKT recipients was 54±18 years (82% females, 27% black Americans, BMI 25±5 kg/m2) and that of HT recipients was 55±14 years (82% females, 27% black Americans, BMI 26±3 kg/m2). As shown in the Figure, BNP values decreased significantly among HKT recipients by 90-days, and remained significantly lower at 1-year post-transplantation (p Conclusion Unlike HT alone, BNP levels were found to be near normal in the majority of HKT recipients within a much shorter period of time and remained low up to 1-year post-transplant. This finding can potentially be explained by improved renal function with kidney transplant ; although, the effect of KT on lusitropic properties of transplanted heart cannot be ruled out.