Early Post-transplant Mortality Research Articles

Pre-transplant Serum Procalcitonin as a Predictor of Early Post-transplant Sepsis and Mortality After Living Donor Liver Transplantation: A Prospective Observational Study.

The early post-transplant period after liver transplantation is critical, as recipients are highly susceptible to sepsis due to their immune-compromised state. This study aimed to identify the association between preoperative procalcitonin and early post-transplant sepsis and mortality at one month after living donor liver transplantation (LDLT). Allpatients who underwent LDLT from July 2021 to December 2021 were recruited prospectively. Participants were divided into two groups based on preoperative PCT levels: elevated (>0.5 ng/ml) and low levels (<0.5 ng/ml). Serum procalcitonin (PCT) levels were measured on the day of transplant and on postoperative days 3 and 7. The relationship between preoperative PCT and post-transplant sepsis was evaluated using a Chi-square test, and receiver operating characteristic (ROC) curves were generated. Sepsis occurred in 48.3% of patients, with a significant association between elevated preoperative PCT levels and early post-transplant sepsis (p=0.023). The ROC curve for preoperative PCT showed moderate predictive ability (area under curve (AUC)=0.664), while PCT levels on postoperative day 3 demonstrated better discriminatory power (AUC=0.790). PCT levels measured on day 7 also had good diagnostic accuracy, with an AUC of 0.843 and a significant difference between the sepsis and non-sepsis groups (p=0.002). The length of ICU stay was significantly longer in the sepsis group (p=0.009). Conclusion: Elevated preoperative PCT levels can predict early post-transplant sepsis in LDLT patients. PCT monitoring may enhance risk stratification and guide perioperative management, improving post-transplant outcomes.

Trends and outcomes of heart transplantation in adults with congenital heart disease.

Heart transplantation for adult congenital heart disease is complicated and associated with challenging pretransplant support, long waiting, and high early post-transplant mortality. We explored if surgical and medical advances, and allocation system changes have affected outcomes. From United Network for Organ Sharing database, adults with congenital heart disease listed for heart transplantation were queried. To explore practice and outcome trends, patients were divided into 4 eras (eras1-3: nearly 3 equal periods from 1992-2018, era-4: after 2018, corresponding with new allocation system). Univariate and multivariable analysis was performed to evaluate outcomes. 2737 patients were listed. There was gradual increase in listed and transplanted patients, along with significant increase in use of mechanical support, simultaneous kidney and liver transplantation. While proportion of transplanted remained constant, there was decrease in proportion delisted/died after listing (p = 0.01) and waiting list duration (p = 0.01), especially in era-4. 30-days post-transplant mortality remains high, however, it has significantly improved starting era-3 (p = 0.01). Current survival at 1-year and 5-years is 85% and 65%, with improvement mainly related to decreased early death. On multivariable analysis, factors associated with survival were lower glomerular filtration rate (HR = 0.99, p = 0.042), bilirubin (HR = 1.17, p < 0.001), and mechanical ventilation (HR = 2.3, p = 0.004). Heart transplantation in adults with congenital heart disease is increasing, along with added complexity, higher usage of pretransplant mechanical support and simultaneous organ transplantation. Despite that, more complex patients don't experience worse outcomes. Early mortality improved but remains high. New donor allocation system allowed shorter waiting time and higher proportion transplanted without altering early mortality.

Predicting Early Post-Transplant Mortality: The Role of ICU Stay in Liver Transplant Recipients with HBV-Related Cirrhosis

Predicting Early Post-Transplant Mortality: The Role of ICU Stay in Liver Transplant Recipients with HBV-Related Cirrhosis

Efficacy and Safety Analysis of Prophylactic Brentuximab Vedotin Administration after Pediatric Acute Leukemia Haploidentical Hematopoietic Stem Cell Transplantation

Objective: Acute graft-versus-host disease (aGVHD) is a common complication following allogeneic hematopoietic stem cell transplantation. Currently, the reported incidence of moderate to severe aGVHD in domestic cases is 13%-47%, while the incidence of grade III/IV aGVHD after haploidentical transplantation ranges from 7.9% to 13.8%. Severe aGVHD is one of the leading causes of early post-transplant mortality. This study aims to analyze whether the administration of Brentuximab vedotin after transplantation can reduce the incidence of aGVHD without increasing disease relapse rates and viral infections. Methods: A retrospective analysis was conducted on 50 pediatric leukemia patients who underwent haploidentical hematopoietic stem cell transplantation (HSCT) at our hospital between June 2017 and July 2022. These patients received prophylactic treatment with Brentuximab vedotin (20mg) on day +1 and day +4 post-transplantation to prevent aGVHD. The median age of the patients was 4.1 years (range: 0.6-16.0 years), with a gender ratio of 25:25 (male:female). At the time of diagnosis, the median white blood cell (WBC) count was 19.9×10 9/L (range: 2.0-863×10 9/L) for 41 patients, while the WBC count at initial diagnosis was unknown for 9 patients. Among the cases, 22 were acute lymphoblastic leukemia (ALL), and 28 were acute myeloid leukemia (AML). Before transplantation, 28 patients were in CR1, 14 in CR2, 2 in CR3, and 6 in NR. All patients received myeloablative conditioning regimens, with 33 receiving Bu/Cy, 15 receiving TBI/Cy, 1 receiving Bu/Flu, and 1 receiving TBI/Flu. The median follow-up time was 29.1 months (range: 3.1-70.1 months). Detailed patient data are presented in Table 1. Results: All 50 patients achieved 100% engraftment of white blood cells, with a median time of 15 days (range: +10 to +21 days). Platelet engraftment occurred in a median time of 9 days (range: +5 to +78 days), except for one patient who did not achieve platelet engraftment. This particular patient was diagnosed with AML and experienced hematologic relapse and extramedullary relapse before transplantation. The patient died due to disease relapse 90 days after transplantation.The incidence of aGVHD after transplantation was 44%, with 28% experiencing grade I-II and 16% experiencing grade III-IV aGVHD. The incidence of CMV viremia was 40%, with a median time to diagnosis of 36 days (range: +19 to +84 days), while the incidence of EBV viremia was 8%, with a median time to diagnosis of 47 days (range: +14 to +87 days). During the follow-up period, five patients experienced disease relapse, with a median time to relapse of 92 days after transplantation (range: +67 to +181 days). Among the relapsed patients, 2 had ALL (both in CR2), and 3 had acute myeloid leukemia (all in NR). Seven patients died during the follow-up, including 4 with AML and 3 with ALL. The causes of death were disease relapse in 3 cases, infection in 2 cases, TMA in 1 case, and cGVHD in 1 case. The estimated 5-year overall survival (OS) and leukemia-free survival (LFS) rates were 86%, and the 5-year cumulative relapse rate was 10% (see Figures 1, 2, and 3). In comparison, a control group of 44 pediatric acute T-cell lymphoblastic leukemia patients who underwent haploidentical transplantation without prophylactic Brentuximab vedotin treatment between January 5, 2021, and June 30, 2022, were analyzed. In the control group, the incidence of aGVHD was 56.8% (P=0.007), with 36.4% experiencing grade I-II and 20.4% experiencing grade III-IV aGVHD. The incidence of CMV viremia was 68.2% (P=0.006), and the incidence of EBV viremia was 29.5% (P=0.007). The relapse rate was 15.9%, and the mortality rate was 27.3%. Conclusion: For pediatric acute leukemia haploidentical HSCT, the administration of Brentuximab vedotin (20mg) on days +1 and +4 after transplantation, in addition to conventional aGVHD prophylaxis (CsA+MMF+sMTX), significantly reduced the overall incidence of aGVHD and grade I-II aGVHD. Administering Brentuximab vedotin on days +1 and +4 did not increase the rates of CMV or EBV infection nor did it increase the risk of disease relapse.

Survival after kidney transplantation compared with ongoing dialysis for people over 70 years of age: A matched-pair analysis

Kidney transplantation offers improved survival and quality of life compared to dialysis for most recipients; however, benefits for elderly patients (>70 years) remain uncertain. Using the Australia and New Zealand Dialysis and Transplant Registry (2009-2019), elderly transplant recipients were matched to a waitlisted dialysis patient by age, cause of end-stage kidney disease, and dialysis duration (paired controls). We censored dialysis patients at the time of transplant. Survival was compared using stratified Cox regression. Elderly transplant recipients (KTRs) (n = 465) were matched to waitlisted pairs. Transplant group mortality initially exceeded dialysis due to excess infection-related deaths (1.9 transplant versus 0.3 dialysis/100 patient-years, P = .03). Beyond month 9, a progressive survival benefit in favor of transplantation was apparent. Over a median follow-up of 1.7 years, mortality was 38% lower for KTRs (95% confidence interval 0.41-0.94, P = .02), and 5-year survival was 80% KTRs vs 53% dialysis (P < .001). Recipients of living and standard criteria donor kidneys acquired immediate survival advantage compared with dialysis, while recipients of expanded criteria donor's kidneys experienced elevated risk of death for the first 17 months. Compared with remaining on dialysis, elderly KTRs incur an increased risk of early posttransplant mortality but thereafter may anticipate progressively superior survival rates.

Contemporary Outcomes of Heart Transplantation in Children with Heterotaxy Syndrome: Sub-Optimal Pre-Transplant Optimization Translates into Early Post-Transplant Mortality.

Patients with heterotaxy syndrome and congenital heart disease (CHD) experience inferior cardiac surgical outcomes. Heart transplantation outcomes are understudied, however, particularly compared to non-CHD patients. Data from UNOS and PHIS were used to identify 4803 children (< 18years) undergoing first-time heart transplant between 2003 and 2022 with diagnoses of heterotaxy (n = 278), other-CHD (n = 2236), and non-CHD cardiomyopathy (n = 2289). Heterotaxy patients were older (median 5yr) and heavier (median 17kg) at transplant than other-CHD (median 2yr and 12kg), and younger and lighter than cardiomyopathy (median 7yr and 24kg) (all p < 0.001). UNOS status 1A/1 at listing was not different between groups (65-67%; p = 0.683). At transplant, heterotaxy and other-CHD patients had similar rates of renal dysfunction (12 and 17%), inotropes (10% and 11%), and ventilator-dependence (19 and 18%). Compared to cardiomyopathy, heterotaxy patients had comparable renal dysfunction (9%, p = 0.058) and inotropes (46%, p = 0.097) but more hepatic dysfunction (17%, p < 0.001) and ventilator-dependence (12%, p = 0.003). Rates of ventricular assist device (VAD) were: heterotaxy-10%, other-CHD-11% (p = 0.839 vs. heterotaxy), cardiomyopathy-37% (p < 0.001 vs. heterotaxy). The 1-year incidence of acute rejection post-transplant was comparable between heterotaxy and others (p > 0.05). While overall post-transplant survival was significantly worse for heterotaxy than others (p < 0.05 vs. both), conditional 1-year survival was comparable (p > 0.3 vs. both). Children with heterotaxy syndrome experience inferior post-heart transplant survival, although early mortality appears to influence this trend, with 1-year survivors having equivalent outcomes. Given similar pre-transplant clinical status to others, heterotaxy patients are potentially under risk-stratified. Increased VAD utilization and pre-transplant end-organ function optimization may portend improved outcomes.

Waiting-List and early posttransplant prognosis among ethnoracial groups: Data from the organ procurement and transplantation network.

Racial/ethnic disparity in waiting-list mortality among candidates listed for kidney transplantation (KT) in the United States remains unclear. We aimed to assess racial/ethnic disparity in waiting-list prognosis among patients listed for KT in the United States in the current era. We compared waiting-list and early posttransplant in-hospital mortality or primary nonfunction (PNF) among adult (age ≥18 years) white, black, Hispanic, and Asian patients listed for only KT in the United States between July 1, 2004 and March 31, 2020. Of the 516,451 participants, 45.6%, 29.8%, 17.5%, and 7.1% were white, black, Hispanic, and Asian, respectively. Mortality on the 3-year waiting list (including patients who were removed for deterioration) was 23.2%, 16.6%, 16.2%, and 13.8% in white, black, Hispanic, and Asian patients, respectively. The cumulative incidence of posttransplant in-hospital death or PNF after KT was 3.3%, 2.5%, 2.4%, and 2.2% in black, white, Hispanic, and Asian patients,respectively. White candidates had the highest mortality risk on the waiting list or of becoming too sick for a transplant, while black (adjusted hazard ratio, [95% confidence interval, CI], 0.67 [0.66-0.68]), Hispanic (0.59 [0.58-0.60]), and Asian (0.54 [0.52-0.55]) candidates had a lower risk. Black KT recipients (odds ratio, [95% CI] 1.29 [1.21-1.38]) had a higher risk of PNF or death before discharge than white patients. After controlling confounders, black recipients (0.99 [0.92-1.07]) had a similar higher risk of posttransplant in-hospital mortality or PNF as white patients than Hispanic and Asian counterparts. Despite having a better socioeconomic status and being allocated better kidneys, white patients had the worst prognosis during the waiting periods. Black recipients and white recipients have higher posttransplant in-hospital mortality or PNF.

Survival and left ventricular dysfunction post lung transplantation for pulmonary arterial hypertension

PurposeBilateral lung transplantation for end-stage pulmonary arterial hypertension (PAH) is traditionally associated with higher early post-transplant mortality when compared with other indications. Changes in perioperative management, including the growing use of perioperative extracorporeal membrane oxygenation (ECMO) and an increased awareness of postoperative left ventricular dysfunction (LVD), have resulted in outcomes that are uncertain. Materials and methodsWe conducted a single-center, retrospective observational study at a lung transplantation center in Melbourne, Australia, from 2006 to 2019. ECMO use was categorized as preoperative, prophylactic, or rescue. Postoperative LVD was defined as a reduction in left ventricular function on echocardiography or using strict clinical criteria. Results50 patients underwent lung transplantation for PAH. 12-month survival was 48/50 (96%). ECMO was used in 26 (52%) patients, and the use of prophylactic VA-ECMO increased over the study period. Postoperative LVD was diagnosed in 21 (42%) patients. 12-month survival and left ventricular function was no different between LVD and non-LVD groups. ConclusionsThis study showed that high survival rates can be achieved following lung transplantation for PAH. We found that ECMO utilization was common, and indications have changed over time. LVD was common but did not impact 12-month survival.

Managing pulmonary arterial hypertension: how to select and facilitate successful transplantation.

Despite improvements in available medical therapies, pulmonary arterial hypertension (PAH) remains a progressive, ultimately fatal disorder. Lung transplantation is a viable treatment option for PAH patients with advanced disease. Recent guidelines from the International Society of Heart and Lung Transplantation (ISHLT) have updated recommendations regarding time of referral and listing for lung transplantation in PAH. The new guidelines emphasize earlier referral for transplant evaluation to ensure adequate time for proper evaluation and listing. They also incorporate objective risk stratification criteria to assist in decision-making regarding timing of referral and listing. With regards to the transplant procedure, bilateral lung transplantation has largely supplanted heart-lung transplantation as the procedure of choice for transplantation for advanced PAH. Exceptions to this include patients with PAH because of congenital heart disease and those with concurrent LV dysfunction. Use of mechanical support via venoarterial ECMO initiated before transplantation and continued into the early postoperative period is emerging as a standard of care and may help to reduce early posttransplant mortality in this population. There has been increased recognition of the importance of WHO Group 3 pulmonary hypertension. Many of the lessons learned from PAH may be applied when transplanting patients with severe WHO Group 3 pulmonary hypertension. Patients with PAH present unique challenges with regards to transplantation that require a therapeutic approach distinct from other lung disorders. Lung transplantations for PAH are high-risk endeavors best performed at centers with expertise in management of both PAH and extracorporeal support.

Intensive regimens of chemotherapy with hematopoetic stem cell rescue in paediatric patients with high-risk malignant tumors

Background. One of the possible options to intensify therapy in patients with high-risk malignant tumors is high-dose chemotherapy (HDCT) with autologous hematopoetic stem cell rescue. However, this method has a high risk of acute and delayed toxicity, and, sometimes doesn’t meet the expected effectiveness. This confirms the necessity of more considerate approach for choosing the category of patients for this therapeutic option with the determination of the most significant factors on the part of the patient and the type of malignant tumor.Objective. Analysis of the results of HDCT with autologous hematopoetic stem cell transplantation (HSCT) in children with high-risk solid malignancies, conducted in the Department of pediatric oncohematology and BMT of the Federal State Budgetary Institution “V.A. Almazov National Medical Research Center”.Design and methods. We perform a retrospective analysis of 55 cycles of HDCT with autologous hematopoetic stem cell rescue provided from 2017 to 2020 in 39 patients with high-risk malignant tumors. The toxicity and efficacy of the method were assessed taking into account the frequency of infectious complications, early post-transplant mortality, event-free (EFS) and overall survival (OS).Results. The predominant category of patients were children with CNS tumors (61.5 %). Mean age of the patients was 2 years 9 months. At the time of HDCT 35.9% of patients were in complete remission (CR), 64.1 % had signs of active disease (AD). In 59% of patients, one course of HDCT was performed, in 41 % — tandem transplantation was performed according to the recommendations of the protocol for the treatment of the disease. The most common conditioning regimen was carboplatin + etoposide (27.3 %). The predominant source of hematopoietic stem cells were peripheral stem cells (87.3 %). The frequency of infectious complications in the post-transplant period was 100 %, neutropenic enterocolitis (61.8 %) and febrile neutropenia (34.5 %) were predominant. A high frequency of reactivation of CMV infection (25.4 %) was noted, meanwhile CMV disease occurred in 35.7 % of cases. The most important prognostic factor was the disease status at the time of HDCT. 2-year OS incidence of 85.7 % vs 65.3% and EFS 85.7 % vs 39 % in patients with CR and AD respectively. After completing the course of HDCT with autologous HSCT 94.8 % of patients continued anticancer therapy.Conclusion. HDCT with autologous HSCT demonstrates a satisfactory toxicity profile and can improve OS and EFS in children with high-risk malignant tumors. A reliable prognostic factor that determines the effectiveness of the method is the disease status at the time of HDCT.

Impact of the new UNOS donor heart allocation system on waitlist outcomes and early posttransplant mortality among adults with congenital heart disease

Adults with congenital heart disease (ACHD) experience worse waitlist outcomes and higher early posttransplant mortality compared to non-ACHD patients. On October 18, 2018; the UNOS donor heart allocation system was redesigned giving unique listing status to ACHD patients. The impact of this change on outcomes in transplant-listed patients is unstudied. Using the Scientific Registry of Transplant Recipients (SRTR) we compared ACHD patients listed for the first-time for heart transplantation from two eras of equal duration. We analyzed waitlist outcomes, posttransplant mortality and length of stay among ACHD patients in both eras and between ACHD and non-ACHD patients in the new era. Of 12723listed patients, 535had ACHD (293 in the new era) and 12188 did not (6258 in the new era). A total of 163 (56%) ACHD patients in the new era versus 150 (62%) in the prior era were transplanted; 11 (3.8%) versus 15 (6.2%) died on the waitlist; 32 (11%) versus 35 (14%) were delisted and 15 (9.2%) versus 19 (12.7%) died within 30days of transplant, respectively. The new UNOS donor heart allocation system improved waitlist time and decreased the proportion not transplanted during the first 300 days after listing among ACHD patients without altering early posttransplant outcomes or significantly changing the gap in outcomes compared to non-ACHD patients.

Matching Donor and Recipient Size in Pediatric Heart Transplantation.

Previous analyses in pediatric heart transplant (HT) recipients using weight or height have not found donor-recipient size-mismatch to be associated with post-transplant mortality. A recent study in 3,215 normal US children developed an equation for left ventricular (LV) mass using body surface area (BSA). We assessed whether donor-recipient size match using predicted LV mass (PLM) is associated with post-transplant in-hospital mortality or 1-year graft survival. We identified 4,717 children <18yrs old who received primary HT in the US during 01/2000 to 03/2015 and divided them into five groups [10%, 10%, 60% (reference group), 10% and 10%, respectively] with increasing donor-recipient PLM ratio. In adjusted analysis, group 1 children (PLM ratio ≤.90) were at higher risk of post-transplant in-hospital mortality [Odds Ratio (OR) 1.55, 95% CI 1.04, 2.31]. This association of the most undersized donors with recipient in-hospital mortality was similar when donor-recipient weight ratio<.88 or BSA ratio<.92 (lowest decile) were used instead. There was no difference in 1-year graft survival among groups. Utilizing donors with donor-recipient PLM ratio ≤.90 is associated with higher risk of early post-transplant mortality in pediatric HT recipients. However, this metric is not superior to donor-recipient weight ratio or BSA ratio for assessing size match.

Early outcomes and long-term survival after kidney transplantation in elderly versus younger recipients from the same donor in a matched-pairs analysis.

The elderly are the fastest-growing population on waiting lists for kidney transplantation (KTx). Recognized barriers to KTx in the elderly is early post-transplant mortality and morbidity. To analyze the outcomes of KTx in recipients older than 60 years and, simultaneously, in their younger paired recipients, receiving a graft from the same donor.We included 328 kidney transplant recipients in the study. The elderly kidney transplant recipients (EKT) group included 164 patients aged 65 standard deviation (SD4) years. They were paired with younger kidney transplant recipients (YKT) aged 45 (SD12) years.The studied groups (EKT vs YKT) did not differ from the graft function estimated 1 year after the transplantation (50.7 mL/min vs 54.0 mL/min), while the estimated glomerular filtration rate decline was significantly faster in the YKT group. One-year patient survival (93.9% vs 97.0%), 1-year graft survival (90.4% vs 82.3%), and incidences of delayed graft function and acute rejection did not differ between the EKT and YKT groups. Significantly more cardiovascular complications and post-transplant diabetes mellitus were noticed in the EKT group. The long-term patient and graft survivals were poorer in the EKT group versus the YKT group, but death-censored graft survivals were the same. After having excluded donor-derived graft factors, there were no differences in the first-year outcome of KTx between recipients younger and older than 60 years. As life expectancy is lower in the EKT group, the probability of patient and graft survival was also significantly lower in this group. However, death-censored graft survival was not different in the EKT and YKT groups.

Abstract 11567: Congenital Heart Disease Classification Improves SRTR Risk Estimation of Waitlist and Early Post-Transplant Mortality for Pediatric Heart Transplantation

Introduction: Risk estimation for waitlist and 1-year post-transplant mortality utilized by SRTR for pediatric heart transplantation dichotomizes patients based upon presence or absence of congenital heart disease (CHD). Hypothesis: Current SRTR risk estimations can be improved by adding further detail in categorization of CHD. Methods: A retrospective analysis of the Pediatric Heart Transplant Society (PHTS) database of pediatric (&lt;18yo) heart transplant listings from 2010 to 2020 was performed, excluding patients listed for retransplantation. Cox hazard models were developed for waitlist mortality during the first year following listing (WaitDeath) and one year post-transplant mortality (TxDeath). The initial model was constructed using covariates included in the current SRTR model and a second model was developed by adding CHD classifications (SRTR+) including: single ventricle vs. biventricular heart disease, ventricular morphology, and surgical interventions. Results: The WaitDeath model included 5,790 patients in which 722 of which died. In the SRTR WaitDeath model, CHD had a HR of 1.8 (95%CI of 1.4-2.3) compared to cardiomyopathy patients. Where as in SRTR+ model, patients with different types of CHD had HR’s that ranged from 1.5 to 2.1 (Table 1). The TxDeath model included 4,185 patients in which 304 which died. (Table 1) In the SRTR model of TxDeath, patients with CHD had a HR of 3.9 (2.9-5.1) compared to cardiomyopathy patients, whereas in the SRTR+ model patients with different types of CHD had HRs that ranged from 2.4-5.3 (Table 1). Conclusions: Inclusion of granular CHD data may improve waitlist and post-transplant mortality risk estimation in pediatric heart transplant patients, allowing for more refinement in allocation policies and understanding of difference in post-transplant outcomes across sites. This data supports further refinement of current SRTR risk adjustment models.

Systemic Immune-Inflammatory Marker of High Meld Patients Is Associated With Early Mortality After Liver Transplantation

The scarcity of deceased donor livers has led to allocation of grafts to only the most seriously ill patients with a high Model for End-Stage Liver Disease (MELD) score, which has resulted in a high mortality rate after deceased donor liver transplantation (DDLT). The aim of this study is to identify risk factors for posttransplant mortality and thereby reduce futile outcomes in DDLT. Between 2013 and 2019, 57 recipients with MELD scores ≥30 underwent DDLT in our center. We retrieved data and identified the risk factors for 90-day posttransplant mortality. The perioperative clinical and laboratory parameters of patients who did or did not survive for 90 days were subjected to logistic regression analysis. Twelve patients died within 90 days. Results of univariate analysis indicated that the differences in patient survival were determined by the amount of intraoperative platelets transfused, the presence of posttransplant septicemia, and systemic immune-inflammation index (SII) at the time of listing with MELD scores ≥30. Multivariate analysis revealed that an SII ≥870 (× 109/L) and posttransplant septicemia were independent risk factors for 90-day mortality. Twenty-two patients had SIIs ≥870, and 13 of these patients had posttransplant septicemia. Of the 13 patients, 90-day mortality occurred in 10 cases. However, in 35 patients with SIIs <870, 90-day mortality due to posttransplant septicemia was recorded only in 1 patient. In conclusion, a preoperative SII ≥870 in a patient with a high MELD score may be a significant risk factor for early posttransplant mortality. Because posttransplant septicemia in patients with high SIIs can lead to fatality, a more intensive effort to prevent infection is needed for patients undergoing DDLT carrying such risk factors to avoid futile liver transplantation.

Non-pulmonarycomplicationsafter lung transplantation: part II.

Lung transplantation (LT) is a viable therapeutic option in the treatment of advanced lung disease. With improvements in post-transplant survival, complications involving different organ systems after LT are increasingly seen. While non-infectious, extrapulmonary complications after LT are not frequently responsible for early post-transplant mortality, they significantly impact the quality of life and long-term survival. These complications are, therefore, becoming increasingly relevant as patients with LT are living longer. These complications encompass almost all organ systems and are driven by a combination of the pre-existing comorbidities, events, and complications around the operative procedure and recovery, and perhaps most importantly, medication side effects of the post-LT regimen. In the first of the two-part review, we covered the general approach to management of extrapulmonary complications and covered specific complications pertaining to cardiovascular, renal, neuropsychiatric, and ophthalmologic organ systems. In the current article, we discuss most relevant complications pertaining to the hematologic, endocrine, and gastrointestinal organ systems. In addition, we discuss two of the most common and consequential complications under the miscellaneous category, namely malignancy and venous thrombo-embolism after LT. These two complications have gained increasing significance in the lung allocation score era where progressively sicker and older patients are being transplanted.

Non-pulmonarycomplicationsafter lung transplantation: Part I.

Lung transplantation (LT) is a viable therapeutic option in the treatment of advanced lung disease. With improvements in post-transplant survival, complications involving different organ systems after LT are increasingly seen. While non-infectious, extrapulmonary complications after LT are not frequently responsible for early post-transplant mortality, they significantly impact the quality of life and long-term survival. These complications are, therefore, becoming increasingly relevant as patients with LT are living longer. These complications encompass almost all organ systems and are driven by a combination of the preexisting comorbidities, events, and complications around the operative procedure and recovery, and perhaps most importantly, medication side effects of the post-LT regimen. We will discuss the wide array of non-infectious extrapulmonary complications after LT in a two-part series of review articles. While we intend to discuss the relevant literature around these complications, there is little in terms of consensus documents to guide the management approach of these complications. We will, therefore, share our experience and learnings that have shaped the management protocols we have in place in an effort to prevent and treat such complications. The goal of the first part of this two-part review is to provide an overview of the most pertinent non-infectious extrapulmonary complications pertaining to cardiovascular, renal, neuropsychiatric and ophthalmologic organ systems.

Long-Term Follow-up of Adult Double Unit Cord Blood (CB) Transplantation (dCBT) Recipients Reveals High Rates of Progression-Free Survival after a Novel Cy/ Flu/ Thio/ TBI 400 Intermediate Intensity Conditioning Regimen

Background: CB transplantation (CBT) can be associated with the advantages of low rates of chronic GVHD & relapse. These benefits, however, can be offset by early post-transplant transplant-related mortality (TRM). Therefore, we have investigated CBT after a novel intermediate intensity, reduced toxicity myeloablative cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 5-10 mg/kg, 400 cGy TBI regimen in an effort to reduce early organ toxicity while also maximizing engraftment & disease control.Methods: We analyzed CBT outcomes, including patient (pt) & graft characteristics associated with TRM, relapse and progression-free survival (PFS), in adult CBT recipients transplanted with this approach. Eligible pts were first allograft recipients </= 65 yrs transplanted for acute leukemia/ MDS/ MPD (</= 10% blasts pre-CBT), B-cell NHL or Hodgkin lymphoma. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine-A/ mycophenolate mofetil (no ATG).Results: 139 consecutive pts [74 (53%) non-European, 84 (60%) CMV seropositive, median age 51 yrs (range 23-65), median weight 83 kg (range 49-136)] were transplanted 10/2007-12/2016. Diagnoses included 102 acute leukemia, 22 MDS/ MPD, 15 B-cell NHL/ HL. All received double unit grafts [median donor recipient 8-allele HLA-match 5/8 (range 2-8), median infused CD34+ dose 1.0 x 105/kg/unit (range 0.2-8.6)]. 54 (39%) CB grafts were supplemented with haplo-identical CD34+ cells as a myeloid bridge. The incidence of CB engraftment was 96% (95%CI: 91-99). Day 180 incidence of grades II-IV & III-IV aGVHD was 78% (95%CI: 70-84) & 21% (95%CI: 15-28), respectively. 1-yr cGVHD was 8% (95%CI: 4-14). Cumulative incidence of day 180 TRM was 12% (95%CI: 7-17) & 21% (95%CI: 14-29) at 3 yrs. 11% (95%CI: 6-18) of pts relapsed by 3 yrs post-CBT. With a median survivor follow-up of 2.7 yrs (range 6.5 months-9.5 yrs), the 3-yr overall survival is 71% (95%CI: 63-80) & PFS is 67% (95%CI: 59-76). 3-yr PFS in 75 acute leukemia CR1 pts is 66% versus 74% in 27 other disease status pts (p = 0.574). 3-yr PFS in 23 FLT-3 mutated AML pts is 83%. The 3-yr PFS is 62% in 22 MDS/ MPD pts & 67% in 15 NHL/ HD pts. The revised disease risk index (rDRI) was not associated with TRM, relapse or PFS (Figure, Table). By contrast, pts with an age adjusted hematopoietic cell transplant-comorbidity index (aaHCT-CI) 0-2 (n = 54) had very low day 180 TRM [4% (95%CI: 1-11)] & high PFS [81% (95%CI: 71-94)] whereas the 85 pts with high aaHCT-CI (median 4, range 3-9) had a day 180 TRM of 17% (95%CI: 10-25) & 3-yr PFS of 58% (95%CI: 48-71). In multivariate analysis of TRM, aaHCT-CI had a HR of 4 (95%CI: 1.4-11.6, p = 0.01) whereas age alone was not significant [HR 1.9 (95%CI: 0.8-4.5), p = 0.12]. In multivariate analysis of PFS, aaHCT-CI HR was 2.4 (95%CI: 1.2-4.7, p = 0.01) whereas for recent pts (CBT 2014-2016) HR was 0.6 (95%CI: 0.3-1.2) although this was not significant (p = 0.17)Conclusions: The 3-yr PFS in this older (median 51 yrs) intermediate intensity dCBT population is very promising. The incidences of cGVHD & relapse are low & DRI was not associated with TRM, relapse or PFS. Notably, addition of haplo-identical cells & better CB HLA-match was not associated with better PFS, & older age (51-65 yrs), CMV sero-positivity & non-European ancestry did not adversely affect PFS. Notably, day 180 TRM in recent pts is 9%. While high aaHCT-CI pts require additional strategies to reduce early post-CBT complications, given PFS is excellent in low aaHCT-CI CBT recipients (39% of pts in this analysis), survival comparisons of intermediate intensity dCBT in this population versus all other HSC sources is warranted. CB can also be attractive in pts with high risk disease given its rapid availability. [Display omitted] Disclosuresvan den Brink:Seres: Research Funding; Therakos Institute: Other: Speaking engagement; PureTech Health: Consultancy; Jazz Pharmaceuticals: Consultancy.

Intraoperative Factors Associated With Early Recipient Death After Adult-to-Adult Living Donor Liver Transplant.

Living donor liver transplant is the gold standard therapy for patients with terminal hepatic disorders for whom no alternative therapy is available. The primary aim was to assess different intraoperative factors that may predict early death after adult-to-adult living donor liver transplant. The secondary aim was to assess the effect of small-for-size syndrome on mortality. This retrospective multicenter cohort study was performed on records from 145 adults with cirrhosis who had received a right lobe living donor liver transplant. Patients were divided according to the occurrence of short-term mortality (death within the first month after transplant). The primary intraoperative parameters included graft weight, surgical duration, mean blood pressure, serum lactate and sodium bicarbonate, transfusions, durations of cold and warm ischemia and anhepatic phase, input and output during surgery, and portal venous pressures. There were statistically significant variations between both cohorts for number of units of packed red blood cells, durations of cold and warm ischemia and anhepatic phase, preclamp and postreperfusion portal venous pressures, average urine output, mean serum lactate, mean blood pressure, and surgical duration (P ⟨ .001). Also, there were significant differences in the number of platelets, units of fresh frozen plasma, and mean sodium bicarbonate (P = .025, .003, and .035, respectively). Of the 25 patients who died within the early postoperative period, 20 had developed small-for-size syndrome (P ⟨ .001). A variety of intraoperative risk factors may affect early posttransplant mortality, which suggests the high complexity of living donor liver transplants and the need for well-trained experienced teams to perform these surgeries.

Impact of the New UNOS Heart Transplant Allocation System on Waitlist and Early Post-Transplant Mortality among Adults with Congenital Heart Disease

<h3>Purpose</h3> Adults with congenital heart disease (ACHD) are more likely to die or be delisted while awaiting heart transplant, less likely to receive a heart transplant and more likely to die in the early (30-day) post-transplant period compared to non-ACHD patients. On October 18, 2018; the UNOS heart allocation system was redesigned providing unique listing status for ACHD patients. The impact of this change on outcomes is unstudied. <h3>Methods</h3> Using the Scientific Registry of Transplant Recipients we compared ACHD patients listed for the first-time for heart transplant from 2 eras of equal duration (new era: October 18, 2018 to June 2, 2020 and prior era: March 3, 2017 to October 17, 2020). Patients with transplants occurring in the new era who were initially listed in the prior era were excluded. We compared baseline characteristics, Kaplan Meier curves and log-rank tests to assess differences in early post-transplant mortality and the composite of waitlist mortality or delisting due to clinical worsening among those with CHD between both eras. <h3>Results</h3> Out of 535 ACHD patients listed, 293 were in the new era (4.7% of total listings) and 242 were in the prior era (3.7%). Age, sex, racial distribution, renal function, hemodynamics and need for ECMO were identical between the two groups. 163 (56%) ACHD patients in the new era versus 150 (62%) in the prior era were transplanted; 11 (3.8%) versus 15 (6.2%) died on the waitlist; 32 (11%) versus 35 (14%) were delisted and 15 (9.2%) versus 19 (12.7%) died within 30 days of transplant respectively. In the new era, ACHD patients were significantly less likely to experience waitlist mortality or delisting due to clinical worsening but had similar early post-transplant mortality compared to the prior era. <h3>Conclusion</h3> The new UNOS heart transplant allocation system improved waitlist outcomes among ACHD patients listed for heart transplant.