Period In Recipients Research Articles

Optimizing the post-CAR T monitoring period in recipients of axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel

AbstractCD19–directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients. Although differences were noted in the incidence and duration of CRS and ICANS between CAR T products, new-onset CRS and ICANS are exceedingly rare after 2 weeks after infusion (0% and 0.7% of patients, respectively). No new cases of CRS occurred after 2 weeks and a single case of new-onset ICANS occurred in the third week after infusion. NRM is driven by ICANS in the early follow-up period (1.1% until day 28) and then by infection through 3 months after infusion (1.2%). This study provides valuable insights into optimizing CAR T therapy monitoring, and our findings may provide a framework to reduce physical and financial constraints for patients.

#1431 Risk factors of adverse cardiovascular events in the early postoperative period in kidney transplant recipients

Abstract Background and Aims Kidney transplantation improves quality of life and increases life expectancy in patients with Stage 5 Chronic Kidney Disease. However, the frequency of adverse cardiovascular events in the postoperative period remains high and reduces the effectiveness of transplantation. The aim was to study the incidence of cardiovascular risk factors in the preoperative period in kidney transplant recipients with adverse cardiovascular events in the early postoperative period. Method The study included 51 kidney transplant recipients whose age was 46.1 ± 4.6 years. 12 (23.5%) recipients had adverse cardiovascular events (acute myocardial infarction, unstable angina, rhythm disturbance, complicated hypertensive crisis) in the early postoperative period. 39 (76.5%) recipients with uncomplicated postoperative period formed the comparison group. The study groups were comparable by gender and age. Results Traditional cardiovascular risk factors were assessed. The study groups had comparable rates of arterial hypertension, obesity, hyperglycemia, dyslipidemia and smoking in the preoperative period and graft function in the postoperative period. The study groups didn't have significant differences in the incidence of anemia and hemoglobin blood concentration. But the erythropoietin blood level in the preoperative period in recipients with adverse cardiovascular events was higher—38.5 (23.5-155.0) mU/mL versus 16.0 (10.0-32.0) mU/mL, p < 0.01, and hypererythropoietinemia was diagnosed more often—58.3% (n = 7) versus 25.6% (n = 10), p < 0.05, than in patients without cardiovascular events. The incidence of elevated interleukin-6 blood level in the preoperative period was higher in recipients with adverse cardiovascular events—25.0% (n = 3) versus 5.1% (n = 2), p < 0.05. At the same time C-reactive protein levels and white blood cell counts were not significantly different. Recipients with adverse cardiovascular events had a lower left ventricular ejection fraction—59.5 ± 10.6% versus 65.6 ± 7.1%, p < 0.05, and a higher incidence of left ventricular diastolic dysfunction in the preoperative period—75.0% (n = 9) versus 35.9% (n = 14), p < 0.05, than in recipients without cardiovascular complications. Conclusion Kidney transplant recipients with adverse cardiovascular events in the early postoperative period had a higher incidence of left ventricular diastolic dysfunction, increased blood levels of erythropoietin and interleukin-6 and a lower left ventricular ejection fraction before transplantation than recipients with an uncomplicated postoperative period.

“Defining the Optimal Post-CART Monitoring Period in Recipients of Axicabtagene Ciloleucel and Tisagenlecleucel”

Background: Rigorous monitoring for approximately 4 weeks after chimeric antigen receptor T-cell therapy (CART) is mandated due the potentially fatal toxicity risks of cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndromes (ICANS) during this period, and to allow early appropriate interventions. The US Food and Drug Administration implemented the Risk Evaluation and Mitigation Strategy (REMS) program for approved CART that mandates patients remain within the proximity of the authorized treating center for the monitoring period. The physical and financial burden of stringent monitoring may pose a barrier to CART access, especially for minorities and patients from rural areas and low-income groups. Therefore, evaluating the optimal duration of monitoring and causes of non-relapse mortality (NRM) is an area of unmet need. We evaluated safety outcomes for commercial axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) recipients. Methods: Patients (pts) ≥ 18 yrs who received an axi-cel or tisa-cel infusion for large B-cell lymphoma between April 2016 and July 2022 at nine academic US medical centers were identified from the Cell Therapy Consortium registry. Descriptive analysis was used to report outcomes. NRM was death due to causes other than disease progression. New-onset CRS and ICANS were reported as a percentage of pts at risk (alive with no prior CRS/ICANS). Results: A total of 374 pts were included with 216 (58%) receiving axi-cel, and 158 (42%) tisa-cel. Demographics are in Table 1. Median follow-up was 12.4 mo (0.3-58) Safety: Any grade CRS occurred in 63% pts, more common in axi-cel recipients (80%) compared to tisa-cel (41%), p<0.0001. During week 1 (Day 0-7), new-onset CRS occurred in 60.4% of the total population including 75.4% of axi-cel and 39.8% of tisa-cel recipients. New CRS onset in week 2 (Day 8-14) was seen in 6.1% of pts (15.4% axi-cel vs 1% tisa-cel). There was no new onset CRS in Week 3 or beyond. The median time to CRS onset was 3 days (0-13). (Figure 1) Unresolved CRS beyond Day 14 occurred in 7.2% (8.7% of axi-cel vs 3.1% of tisa-cel recipients), of which only 1.7% of pts (all axi-cel recipients) had unresolved CRS beyond Day 28. The median time to resolution was 4 days (IQR 25-75%: 2-7). 98.3% of CRS resolved by Day 28. Any grade ICANS was seen in 35% of pts, more common in axi-cel (52%) compared to tisa-cel (10%), p<0.0001. During Week 1, new-onset ICANS was seen in 27% of of the total population including 40.7% of axi-cel and 8.2% of tisa-cel recipients. New ICANS in week 2 was seen in 9.5% of pts (18.8% of axi-cel vs 2.8% of tisa-cel recipients). During week 3, new-onset ICANS occurred in only 1 tisa-cel recipient (0.4%). There were no new cases in week 4 and beyond. The median time to ICANS onset was 5 days (1-21). Unresolved or ongoing ICANS beyond Day 14 occurred in 32.8% of pts (34.8% of axi-cel: vs 18.7% of tisa-cel recipients), and beyond Day 28 in 7% of pts (7.1% of axi-cel vs 6.3% of tisa-cel recipients). The median time to ICANS resolution was 12 days (IQR 25-75%: 9-16). 93% of ICANS resolved by Day 28. Toxicity Management: Tocilizumab was utilized in 47% of pts (axi-cel 62% vs tisa-cel 26%) and 33% of pts received steroids (axi-cel 50% vs 10% tisa-cel) for management of CART-related toxicities. Other Complications: Infectious complications from Day 0-28 were seen in 18.5% of the total population and more commonly in axi-cel (22%) compared to tisa-cel (13.9%) recipients, p=0.006. Grade ≥4 neutropenia from Day 0-28 days was seen in 66% of the total population (81% axi-cel vs 46% tisa-cel). 82% of the total population did not have Grade ≥4 neutropenia beyond Week 2, and 93% had no Grade ≥4 neutropenia beyond Week 4. NRM: Day 0-28 NRM included 4 deaths (3 related to ICANS and 1 infection), and Day 29-90 NRM included 7 deaths (3 infections, 1 ICANS, 1 cardiac, 2 other). Conclusions: This large multicenter retrospective analysis evaluates patterns of CRS, ICANS, and NRM in recipients of axi-cel and tisa-cel. While NRM is mainly due to infections and ICANS, our study suggests that beyond 2 weeks following CART infusion, the incidence of new onset CRS and ICANS is low. This data supports further investigation into individualized monitoring strategies for stable patients. A flexible monitoring period may help to decrease the financial and physical burden for patients and make CART more accessible and feasible, especially for those with limited socioeconomic support.

SP5.2.1 Renal Transplant Outcomes Through the COVID-19 Pandemic at a London Transplant Centre

Abstract Aims The aim of this audit was to establish the impact of COVID-19 on the outcomes of renal transplant recipients in the post-transplant period at our centre, through the 2020 calendar year. Methods Living donor and deceased donor renal transplant recipients in the period of interest were identified and any complications or adverse outcomes were reviewed and compared to outcome data from the previous year. Results A total of 88 renal transplants were performed in 2020. Fifty-five cases were performed after reopening the Unit. Five patients tested positive for COVID-19 in the post-transplant period. One patient was admitted to the Intensive Care Unit and subsequently died from related complications. Another patient suffered from internal jugular vein thrombosis shortly after testing positive and could be attributed to the hypercoagulable state post-infection. A total of 4 deaths and 1 graft loss were recorded within 2020. This compares to 1 death, 2 graft losses and 1 primary non-function in 172 transplants in 2019. Of the 4 deaths, one was directly linked to COVID-19. The other 3 deaths could be indirectly linked to the disruptions that were made in the healthcare system during this period in adapting to the pandemic. Conclusions It was anticipated that COVID-19 will directly and indirectly affect patient outcomes from surgery during this period. This was clearly seen at this Unit, with mortality rates having increased almost eight-fold in the post-transplant period compared to the same period in the previous year. However, no significant difference was seen with graft losses.

Monocyte-to-High-Density Lipoprotein Cholesterol Ratio Is Independently Associated With All-Cause Mortality in Deceased Donor Kidney Transplant Recipients.

The primary objective of this study was to evaluate the impact of monocyte-to-high-density lipoprotein cholesterol ratio on all-cause mortality in deceased donor kidney transplant recipients. This was a retrospective observational study in which all deceased donor kidney transplant recipients were included. Relevant data for analyses included clinical and demographic features, laboratory values, number of HLA matches, occurrence of delayed graft function, cold ischemia time, and survival status. Kaplan-Meier survival analysis and Cox proportional hazards analysis were performed to determine the effects of monocyte-to-high-density lipoprotein cholesterol ratio on all-cause mortality. Our study included 325 deceased donor kidney transplant recipients (43.1% females, mean age of 44.5 ± 11.2 years). Median value of monocyte-to-high-density lipoprotein cholesterol ratio was 14.0 (interquartile range, 9.94-21.03). The total median observation time was 227 weeks (range, 115-345 weeks). Twenty deaths (12.3%) occurred during the follow-up period in recipients with monocyte-to-highdensity lipoprotein cholesterol ratio below median value, whereas 47 deaths (29%) occurred in recipients with ratio above the median (P < .001). Log-rank test showed significantly higher mortality in the group with monocyte-to high density lipoprotein cholesterol ratio higher than median (P = .001). In the multivariate Cox model, delayed graft function, duration of dialysis, cold ischemia time, and monocyte-to-high-density lipoprotein cholesterol ratio group appeared as independent predictors of all-cause mortality. Monocyte-to-high-density lipoprotein cholesterol ratio before kidney transplant seems to affect survival independently in deceased donor kidney transplant recipients.

Split liver transplantation in two recipients for urgent indications: an example and logistics of interregional cooperation

Aim. To report a rare case of split liver transplantation in two urgent recipients treated in hospitals that are very far from each other. Material and methods. Partial liver grafts were obtained by controlled full-right/full-left in situ splitting. The left lobe was transplanted in a 7-year-old child with severe hepatic failure (PELD score 39) resulting, probably from an progressive intrahepatic familial cholestasis in Novosibirsk. The right lobe was used for re-transplantation in a 28-year-old patient with hepatic artery thrombosis (UNOS status 1A) after living donor right lobe liver transplantation in Moscow. Results. The course of the early post-operative period in recipient 1 was complicated by infected total pancreatonecrosis with the development of limited biliary leakage and the formation of a stricture, which required reconstructive cholangiojejunostomy 12 months after transplantation. Recipient 2 consistently underwent biliary leakage, arrosive arterial bleeding, graft artery thrombosis, all of which could become fatal. Complications were successfully eliminated by the consistent use of surgical and endovascular interventions. Conclusion. The presented observation is, firstly, an example of effective inter-center cooperation, and secondly, a demonstration of the existing problems of postmortem organ donation, which determine the need for such extreme surgery in critical situations.

Argatroban Bridging in the Immediate Post-Operative Period in Recipients of Durable Left Ventricular Assist Devices

Purpose In recipients of durable LVADs, the development of heparin induced thrombocytopenia threatens the integrity of the pump circuit and thus the life of the patient. In hospitalized HF patients, the exposure to heparin is frequent and often prolonged. We set out to change our immediate bridging protocol post-LVAD to decrease heparin exposure and evaluate the bleeding and thromboembolic consequences of these 2 different bridging strategies. Methods This is a single center retrospective study of consecutive patients implanted with a durable LVAD. Heparin (HEP) bridging was utilized in patients from Jan 2016 to June 2017 (n=30) and argatroban (ARG) bridging was utilized in patients from July 2017 through June 2018. Patients that received an RVAD at time of LVAD implantation were excluded from the analysis. Patients were started on intravenous anticoagulation the morning of POD#1 and were titrated to goal (heparin anti-factor Xa levels 0.3 to 0.5; argatroban PTT 50-70 s.) Aspirin and warfarin were also initiated on POD#1. Events were tracked 6 months post-implant. Results Device selection between the two groups was different with the following breakdown; HEP group with 27 HM2 and 3 HVADs compared to the ARG group with 11 HM2, 15 HVADs and 3 HM3. The need to return to the OR from bleeding was lower in the ARG group (6.4% vs 23.3%, p=0.27). The mean number of red blood cell transfusions was statistically lower in the ARG group (1.5 vs 2.7 units, p=0.02). There was no difference observed between the platelet counts on POD#3 or POD#7. A nonsignificant reduction in major hemolysis between the two groups was noted (HEP 20.0% vs ARG 3.2%, p=0.10). There was 1 patient with pump thrombosis in the ARG group compared to 2 patients in the HEP group. A nonsignificant increase in strokes was observed in the ARG group (overall 25.8% - 19.3% ischemic stroke; 6.5% hemorrhagic stroke) compared to the HEP group (overall 16.6% - 13.3% ischemic; 3.3 hemorrhagic stroke; p=0.58) Conclusion Argatroban bridging in the immediate post-operative period is safe in recipients of durable LVADs. There were fewer bleeding events in the ARG bridged group. Though not meeting statistical significance, there were numerically more episodes of major hemolysis and pump thrombosis in the HEP group which contrasted with more stroke events in the ARG group.

Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study

To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). Cohort study within a multicenter, double-masked, randomized clinical trial. One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n= 675) or 8 to 14 days (n= 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. Graft success at 3 years. One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

Postoperative changes in neutrophil-to-lymphocyte ratio and platelet count: A simple prognostic predictor for adult-to-adult living donor liver transplantation

The neutrophil-to-lymphocyte ratio (NLR) is a simple index that represents systemic inflammatory change. The number of platelets is also known to reflect both post-transplant graft regeneration and dysfunction. Thus, we aimed to investigate the usefulness of NLR and platelet number in predicting the clinical course after adult-to-adult living donor liver transplantation (AA-LDLT) in the acute postoperative period in recipients. Between January 1999 and December 2013, 61 patients underwent their first AA-LDLT at our institute. We retrospectively analyzed their clinical data, including NLR and number of platelets, until postoperative day 14, and evaluated their ability to predict prognosis after AA-LDLT. The optimal cutoff values of postoperative maximum NLR and maximum platelets to predict prognosis were 50 and 80×103/μL, respectively. The 1- and 5-year survival rates were 87.5% and 79.1% in the normal maximum NLR group, respectively, and 46.2% for both in the high maximum NLR group (p=0.0033). The 1- and 5-year survival rates, respectively, were 90.9% and 84.1% in the high maximum platelets group and 47.1% and 41.2% in the low maximum platelets group (p<0.0001). In multivariate analysis, maximum NLR≥50 and maximum platelets<80×103/μL were independently associated with 1-year mortality. A high NLR and a low platelet count during acute postoperative period might correlate with poor prognosis after AA-LDLT.

Functional hepatic venous outflow and its correlation with early graft function in live donor liver transplantation

Introduction: To evaluate the effect of central venous pressure (CVP) on early graft function in live donor liver transplantation (LDLT). Methods: 61 Recipients of LDLT without any technical complications from May 2013 to November 2014 were included. CVP was measured at five time points – before surgery, anhepatic phase, 30 minutes after reperfusion, end of surgery and post operatively (days 1–5). Patients were divided into two groups based on CVP ≤10, >10 mm Hg at various time points for analysis. Results: Elevated postoperative CVP (p ≤ 0.001) and drain culture positivity in the first week (p < 0.001) were found to be independent predictors of mortality on multivariate analysis. Optimum cut off of CVP in predicting mortality is 10.8. High cardiac output at the end of surgery (p = 0.005), high MELD scores (p = 0.011) and culture proven infection at any site (p = 0.002) were all independent predictors of early graft dysfunction (EGD) on multivariate analysis. There was an inverse correlation between CVP and SVR at the beginning of surgery which reversed to a positive correlation at the end of surgery. Conclusions: Elevated CVP in the postoperative period in recipients is a risk factor of mortality in the setting of LDLT. EGD is associated with high MELD scores, higher cardiac output at the end of surgery and infection at any site. A restrictive fluid management protocol aiming for a CVP <11 seems beneficial.

Comparison of the Clinical Outcomes between Anti-thymocyte Globulin and Basiliximab Induction Therapy in Deceased Donor Kidney Transplantation: Single Center Experience

Background: The aim of this study is to evaluate the clinical outcomes between anti-thymocyte globulin (ATG) and basiliximab induction in deceased donor kidney transplantation (DDKT). Methods: Between May 2006 and February 2015, 40 patients underwent DDKT at our institution. Three cases (7.5%) of them were lost during the following-up schedule. In this study, ATG induction criteria were donor age >50 years old or donor creatinine level >1.3 mg/dL except hepatitis B virus positive and hepatitis C virus positive recipients. Recipients were divided into two groups: the ATG group (n=20) and the basiliximab group (n=17). Results: The 1-year patient survival in the ATG group was 89.4% compared to 93.8% in the basiliximab group (P=0.989). Graft survival for a 1 year in the ATG and the basiliximab group was 89.1% and 93.8%, respectively (P=0.967). Incidences of acute rejection episodes were more prevalent in the basiliximab group (15.0% vs. 29.4%, P=0.428). The glomerular filtration rate level by period of recipients was not different in both group (12th month, 64.60±16.17 mg/dL vs. 68.51±18.60 mg/dL, P=0.544). The overall complications during the follow-up were not significantly different in both groups (90.0% vs. 76.5%, P=0.383). Conclusions: The results showed that there was no difference in the patient survival and graft survival between induction of ATG and basiliximab of the DDKT were not different. Therefore, use of both induction agents led to a good patient and graft survival and ATG might be a safe and preferable agent for relatively poor renal function of donor in kidney transplantation.

Pneumocystis Jirovecii Pneumonia In Recipients Of Autologous Hematopoietic Stem Cell Transplantation: A 10-Year Cohort Study

▪ BackgroundPneumocystis jirovecii pneumonia (PJ), previously known as Pneumocystis carinii (PCP), is a potentially life-threatening disease in immunocompromised patients. The at-risk population includes patients with HIV infection and low CD4 counts, hematological malignancies, hematopoietic stem cell (HSC) and solid organ transplant recipients, and patients receiving glucocorticoids or other immunomodulatory agents. The highest-risk group of immunocompromised patients tends to be those with HIV (human immunodeficiency virus) infection, where PJ follows an indolent course. However, in non-HIV immunocompromised patients, such as HSC transplant recipients, the infection tends to present with respiratory failure. The incidence of Pneumocystic jirovecii pneumonia (PCP) in autologous BMT (bone marrow transplant) has not been clearly determined, and the indication for prophylaxis in this setting remains unclear. In this study we evaluate the incidence of PJ infection over a 10-year period in recipients of autologous transplants. MethodsRetrospective analysis of 1191 consecutive autologous HSC transplants performed between 1/1/2000 and 6/30/2011 at the University of Michigan Blood and Marrow Transplantation Program. The data was obtained from the BMT Program Database at The University of Michigan Comprehensive Cancer Center. The diagnosis of PJ pneumonia was established by both bronchoscopy with brochoaveolar lavage (BAL) with polymerase chain reaction (PCR). We analyzed the following risk factors for the development of PJ pneumonia: diabetes, glucocorticoid use (in the setting of primary disease relapse, chemotherapy-induced pneumonitis, or idiopathic thrombocytopenic purpura), infections (Pseudomonal urinary tract infection, candidiasis, herpes simplex virus), cutaneous T-cell lymphoma, hypertension, and seizure disorder. ResultsA total number of 5 PJ infections were diagnosed during study period, resulting in a cumulative incidence incidence of 0.42% (95%CI [0.136449% -- 0.976969%]) over the 10 year period. All cases occurred between 2001 and 2006, and 3 months or later following transplantation. Most patients (n=4) were older than 50 years old, and all of them were on steroids. Diagnoses included non-Hodgkin's lymphoma (n=3), Hodgkin's lymphoma (n=1) and multiple myeloma (n=1). Conditioning regimen was BEAM (BCNU, etoposide, cytarabine, melphalan, n=4) and high dose melphalan (n=1). Only 2/5 patients were neutropenic at the time of the pneumonia, and this did not correlate with the CD34+ cell infused, which was ≥2.2x10E6/kg for all patients. Four patients were on corticosteroids for relapsed lymphoma (n=2), ITP (n=1), BCNU pneumonitis (n=1). The remainder patient was on florinef and was coinfected with candida and herpes virus. There were no particular comorbidities associated with the diagnosis of PJ pneumonia. One patient died of PJ, the remainder were treated successfully. ConclusionThis is the largest cohort of patients undergoing autologous transplantation evaluated for PJ pneumonia over a long period of time. Our low incidence and successful therapy suggest that PJ prophylaxis is not routinely warranted in patients undergoing autologous HSCT. Special consideration may be given to patients with additional risk factors such as corticosteroids. Disclosures:No relevant conflicts of interest to declare.

Kidney Graft Survival Rates Do Not Improve by Era: The Impact of the Age Factor

We performed this study to evaluate whether older ages of donors and recipients negatively affected long-term graft survival. We compared 5-year graft survival rates of 89 recipients transplanted between 1991 and 1995 (period A) versus 221 recipients transplanted between 1996 and 2000 (period B). Acute rejection rates and the number of donors and recipients >50 years of age were compared in the two periods. The 5-year graft survival rate in period B was 76.3% versus 82% in period A. In period B, the acute rejection incidence was 18% versus 40% in period A ( P < .001). The overall 5-year graft survival was 86.2% for donors aged 21–50 years and 65.7% for donor's aged >50 years ( P < .0001) in period A versus 84.1% and 68%, respectively, in period B ( P = .0023). In period A, 23.6% of donors and 35.9% of recipients were >50 years old, versus 50.2% and 42.9%, respectively, in period B. The graft survival rate in period B was worse than in period A, although the acute rejection rate was lower. The older age of both donors and recipients in period B seemed to be an important cause of worse outcomes.

Portal pressure &lt;15 mm Hg is a key for successful adult living donor liver transplantation utilizing smaller grafts than before

To prevent small-for-size syndrome in adult-to-adult living donor liver transplantation (A-LDLT), larger grafts (ie, right lobe grafts) have been selected in many transplant centers. However, some centers are investigating the benefits of portal pressure modulation. Five hundred sixty-six A-LDLT procedures using right or left lobe grafts were performed between 1998 and 2008. In 2006, we introduced intentional portal pressure control, and we changed the graft selection criteria to include a graft/recipient weight ratio >0.7% instead of the original value of >0.8%. All recipients were divided into period I (1998-2006, the era of unintentional portal pressure control; n = 432) and period II (2006-2008, the era of intentional portal pressure control; n = 134). The selection of small-for-size grafts increased from 7.8% to 23.9%, and the selection of left lobe grafts increased from 4.9% to 32.1%. Despite the increase in the number of smaller grafts in period II, 1-year patient survival was significantly improved (87.9% versus 76.2%). In 129 recipients in period II, portal pressure was monitored. Patients with a portal pressure <15 mm Hg demonstrated better 2-year survival (n = 86, 93.0%) than patients with a portal pressure >or=15 mm Hg (n = 43, 66.3%). The recovery from hyperbilirubinemia and coagulopathy after transplantation was significantly better in patients with a portal pressure <15 mm Hg. In conclusion, our strategy for A-LDLT has changed from larger graft-based A-LDLT to controlled portal pressure-based A-LDLT with smaller grafts. A portal pressure <15 mm Hg seems to be a key for successful A-LDLT.

Increased Interleukin-10 Production Without Expansion of CD4+CD25+ T-Regulatory Cells in Early Stable Renal Transplant Patients on Calcineurin Inhibitors

Increasing long-term allograft survival is the main challenge in organ transplantation, and allograft loss due to chronic rejection has been found to correlate with episodes of early acute rejection. It is important to understand the mechanisms that maintain the donor-specific hyporesponsive state. This study prospectively evaluates immune events related to donor-specific hyporesponsiveness in the stable transplant patients on calcineurin inhibitors (CNIs). Peripheral blood mononuclear cells of transplant recipients on CNI (n=19) were tested in mixed lymphocyte reaction (MLR) against donor and third-party peripheral blood mononuclear cells pretransplant and at 6 to 8 weeks, 14 to 18 weeks, and 6 to 8 months posttransplant. Interleukin (IL)-10 and transforming growth factor-beta were quantitated in cultures supernatants by enzyme-linked immunosorbent assay. CD4CD25 T-regulatory cells (Tregs) were enumerated using flow cytometry. All patients showed sharp decline in anti-donor and third-party MLR response at 6 to 8 weeks posttransplant with progressive decline up to 6 to 8 months. This was accompanied by increased IL-10 levels in the supernatant at all the follow-ups. Transforming growth factor-beta level in the supernatant was significantly lower at 14 to 18 weeks. Frequency of CD4CD25 Tregs showed a significant decrease at 6 to 8 weeks posttransplant, which was sustained up to 6 to 8 months. The study shows that the maintenance of good graft function in early posttransplant period in recipients on CNI is associated with a decrease in donor-specific and third-party MLRs. There is a decline in Treg numbers along with increased IL-10 levels. High IL-10, probably from a non-Tregs source, may have an important role in maintaining hyporesponsiveness and good graft function.

Caspofungin‐resistant Aspergillus flavus after heart transplantation and mechanical circulatory support: a case report

Invasive aspergillosis (IA) is a severe complication in the post-transplant period in recipients of solid organs. Therefore, early diagnosis and specific therapy of fungal infections in these patients are indispensable. We report the case of a 49-year-old patient, who suffered from IA after cardiac transplantation, which was complicated by post-transplant right heart failure requiring mechanical circulatory support using veno-arterial extracorporeal membrane oxygenation and a right ventricular assist device. Despite antifungal treatment, the patient died 3 weeks after transplantation because of multi-organ failure secondary to IA. The isolated Aspergillus strains exhibited in vitro resistance to caspofungin.

Normal Hepatic Hemodynamics During Early Postoperative Period in Recipients With Adult Live Donor Liver Transplantation

To recognize “normal” hepatic hemodynamics after live donor liver transplantation (LDLT), we analyzed Doppler parameters on recipients with a right liver graft and donors after extended left hepatectomy. Theoretically these values should be the same. From April 2000 to October 2004, 20 LDLTs were performed using a right liver graft. The 10 recipients without postoperative complications and their donors were included in this study. Portal venous velocity (PVV; cm/s), hepatic arterial peak systolic velocity (cm/s), and hepatic venous peak velocity (HVPV; cm/s) were measured during the first 2 weeks. In donors PVV and HVPV after LDLT were significantly higher after than before left hepatectomy: 19.2 ± 4.2 vs. 31.5 ± 13.0 cm/s ( P = .013) and 23.0 ± 7.2 vs. 41.8 ± 10.3 cm/s respectively ( P = .010). However, there were mild degrees of increased PVV and HVPV. In recipients, a markedly increased PVV (106.3 ± 45.2 cm/s on day 1) was significantly higher than that in donors on each postoperative day. The hepatic arterial resistive index in recipients was also significantly higher than that in donors on each postoperative day, for example, 0.72 ± 0.11 vs 0.62 ± 0.04 on day 1 ( P = .0326). In conclusion, we have shown “abnormal” hepatic hemodynamics in even those recipients without complications during the early postoperative period after LDLT.

Model for End-Stage Liver Disease Score-Based Allocation of Donors for Liver Transplantation: A Spanish Multicenter Experience

Prioritizing the liver transplant waiting list (WL) is subject to great variability. We present the experience of four transplant centers in Andalusia (Southern Spain) with a new consensus model of WL management based on the Model for End-Stage Liver Disease (MELD) score. The initial criteria for local prioritizing were: a) cirrhosis with MELD score > or =24, and b) all hepatocellular carcinoma (HCC) admitted to the WL. Fourteen months later new criteria were established: a) cirrhosis with MELD score > or =18, and b) uninodular HCC between 3-5 cm or multinodular HCC (2-3 nodules <3 cm). Access to regional priority was scheduled after three months for patients with cirrhosis or six months for patients with HCC. We analyzed the WL mortality rate, posttransplant survival rate, and overall survival rate over three 14-month periods: A (before implementation of priority criteria), B (initial criteria), and C (current criteria). Priority was given to 36% of recipients in period B and 47% in period C. The WL mortality rate (including removals from WL) was 12.9%, 12.9%, and 10.7% in periods A, B, and C, respectively. One-year graft survival was 79.7%, 72.6%, and 81.2% in the same periods. The overall one-year survival rate for new cases on the WL was 74.9% in period A, 68.6% in period B, and 82.2% in period C. The allocation system and WL management with the current criteria resulted in lower waiting list mortality without reducing posttransplant survival, leading to better survival for all patients listed.

Low molecular weight dextran sulfate prevents the instant blood-mediated inflammatory reaction induced by adult porcine islets.

One of the main obstacles to clinical islet xenotransplantation is the injurious instant blood-mediated inflammatory reaction (IBMIR) that causes rapid binding of platelets to the islet surface, activation of the coagulation and complement systems, and leukocyte infiltration of the islets when the islets are exposed to blood. This study assesses the effect of low molecular weight dextran sulfate (LMW-DS) on IBMIR induced by porcine islets in an in vitro tubing loop assay using human blood and in an in vivo model using diabetic athymic mice. In vitro experiments demonstrated that platelet consumption, coagulation, and complement activation were already reduced in the presence of LMW-DS at 0.01 mg/mL, and that at 0.1 mg/mL, LMW-DS prevented IBMIR. Immunohistochemical investigation showed that the leukocyte infiltration was abrogated at the highest dose. In vivo experiments showed that the transplanted pig islets survived for a significantly longer period in recipients treated with LMW-DS, and morphologic examination of transplanted islets showed a reduction in IBMIR analogous to that demonstrated by in vitro studies. Given that LMW-DS has been used in clinical studies without serious adverse reactions, it has potential as a drug candidate that can control the strong innate immune response induced by pig islets when transplanted through the portal vein.

Critical islet mass for successful porcine islet autotransplantation.

A major reason for the failure of clinical islet transplantations may be a limited islet mass. The aim of this study was to determine the critical islet mass necessary for normalization of glucose metabolism in a porcine model. Diabetes was induced by total pancreatectomy. The splenic lobe of the pancreas was intraductally distended with UW-solution containing 2.67-3.33 mg/ml collagenase, and the distended pancreas was digested in a continuous digestion filtration device. The islets were purified on a isoosmotic Ficoll-sodium-diatrizoate gradient. The survival period of the diabetic recipients in group 2 and 3 receiving, respectively, a low (2.14+/-0.39 microL/kg body weight) and a high (4.99+/-0.83 microL/kg body weight) islet mass was significantly prolonged compared to that of diabetic recipients in group 1 receiving no islet transplantation. However, the survival period of the recipients in group 2 was not significantly different to that in group 3. Three recipients of an islet mass of >5 microl/kg body weight became normoglycemic (fasting blood glucose <100 mg/dl) for more than two months. Furthermore, the glucose and insulin release reactions to the glucose challenge were comparable to that before pancreatectomy. Contrarily, another five diabetic recipients of an islet mass of <4 microL/kg body weight became a fasting blood glucose level of <200 mg/dl. The glucose and insulin release reactions to the glucose challenge were improved only, but not normalized compared to that before pancreatectomy. The data presented in this study demonstrate that metabolic normalization in pancreatectomized diabetic minipigs can be established by autotransplantation of an islet mass of >5 microl/kg body weight.