Era Of Transplantation Research Articles

A New Prognostic Scoring System for Multiple Myeloma in the Era of Novel Agents and Autologous Stem Cell Transplantation: A Multicenter Retrospective Collaborative Study of the Japanese Society of Myeloma

Multiple myeloma (MM) is a heterogeneous disease in the survival outcome due to the differences in disease-, patient-, and treatment-related prognostic factors. Recently, a Revised International Staging System (R-ISS) incorporating the original ISS stage, high serum LDH, and adverse cytogenetic abnormalities (CA) such as [t(4;14), t(14;16), or del(17p)] by FISH, which is expected to predict treatment outcome more accurately in the era of novel agents and autologous stem cell transplantation (ASCT), has been proposed. However, it has been noted that more than 60% of myeloma patients are doomed to be classified as R-ISS stage II, which may encompass heterogeneous population in terms of risk factors. In the present study, we have evaluated the clinical relevance of R-ISS in Japanese patients with MM and invented a new prognostic scoring system to minimize the heterogeneity of the R-ISS stage II. Clinical features of the patients diagnosed and treated between 2001 and 2012 by the members of the Japanese Society of Myeloma were collected and assessed for the treatment outcome. Among the individual data obtained from 4138 patients from 38 centers, only those of 718 patients were complete and were further analyzed. A total of 498 patients (69.4%) were treated with conventional chemotherapy with or without novel agents without ASCT, and the remaining 220 patients (30.6%) were treated with ASCT after induction with chemotherapy with or without novel agents. The patient distribution according to R-ISS stages (I/II/III) was 154 (21.4%), 438 (61.1%), and 126 patients (17.5%), respectively, with corresponding median overall survival (OS) being 152.8, 65.2, and 45.3 months, respectively (p=8.98e-15). Although the R-ISS model could discriminate the difference between each stage distinctly in transplant-ineligible patients (median OS: stage I, 90.7; stage II, 57.5; and stage III, 33.1 months, respectively, p=2.37e-12), discrimination of the difference between the stages II and III was ambiguous in transplant-eligible patients (median OS: stage I, not reached; stage II, 71.2; and stage III, 73.8 months, respectively, p=0.0325). In addition, median OS of R-ISS stage II were quite heterogeneous according to the presence or absence of risk factors (high LDH and adverse CA): 74.2 months for ISS stage I with 1 risk factor of either LDH or CA, 34.0 months for ISS stage I with both risk factors, 130.8 months for ISS stage II without risk factors, 53.8 months for ISS stage II with 1 risk factor, 46.9 months for ISS stage II with both risk factors, and 61.8 months for ISS stage III without risk factors. These results would implicate that high LDH and/or adverse CA might exert stronger impact on OS. Accordingly, we performed a multivariate analysis to disclose more important factors that were independently associated with poor prognosis, and identified the following factors: serum albumin (<3.5 g/dl, p=0.014), b2-microglobulin (≥3.5 mg/l, p=0.0044), high LDH (>normal upper limit, p<0.00001), adverse CA by FISH (p=0.0006), and abnormal karyotype by G-banding (p=0.023). As a result, high b2-microglobulin (n=367, 51.1%), high LDH (n=139, 19.4%), and adverse CA by FISH (n=198, 27.6%) were determined to be significant important factors to be incorporated into the design of more realistic prognostic scoring system. By using these newly identified 3 risk factors (high b2-microglobulin, high LDH, and adverse CA), we have established a brand new scoring system as the Japanese Prognostic Scoring System (JPSS). By applying this scoring system, 232 (32.3%), 297 (41.4%), 160 (22.3%), and 29 patients (4.0%) were assigned to score 0, 1, 2, and 3, respectively. Median OS according to this scoring system (0/1/2/3) were 130.8, 62.4, 49.5, and 37.5 months, respectively (p=2.1e-20, Figure 1). Importantly, this scoring system is able to clearly discriminate the difference in OS between the stages both in transplant-eligible and -ineligible patients (p=2.81e-14 and p=0.000153, respectively). When the same patients were assigned to score 0, 1, and ≥2 by combining the data of scores 2 and 3, median OS of each group became 130.8, 62.4, and 47.7 months, respectively (p=1.29e-19). Thus, we hereby propose a JPSS comprising three prognostic factors as a simple and useful model for the risk assessment of Japanese patients with MM in routine practice that warrants further validation in larger studies. [Display omitted] DisclosuresSunami:Celgene Co. Ltd.: Research Funding; Research funding from Ono Pharmaceutical Co. Ltd., Novartis Pharmaceutical Co. Ltd.: Research Funding; Takeda Pharmaceutical Co. Ltd.: Research Funding; Ono Pharmaceutical Co. Ltd.: Research Funding.

Second Blood or Marrow Transplant (BMT) for Relapse: Mismatch Haplotype Switch May Improve Outcome

Introduction: With improvements in supportive care, including graft-versus-host disease (GVHD) control, relapse has become the major complication of allogeneic BMT. The use of haploidentical donors often allows the potential to select a different donor for the second transplant. We examined the outcomes of patients who underwent a second BMT for relapse at Johns Hopkins between 2005 and 2014. We hypothesized that if loss of heterozygosity is a mechanism for relapse after haploBMT, then utilizing a donor that recognizes the other shared haplotype could improve antitumor activity and thus overall survival (OS). In the case of a failed matched transplant, recognition of a non-shared haplotype on the tumor by the second allograft would be beneficial.Methods: We identified all patients who received a second transplant for relapse of a hematologic malignancy between 2005 and 2014. Acute GVHD (aGVHD) is reported as Glucksberg grades 1-4; chronic GVHD (cGVHD) is reported as limited or extensive. GVHD and non-relapse mortality (NRM) was calculated via cumulative incidence (CI) with competing risk analysis. OS was calculated as the time from second transplant to death or last known follow-up and estimated using the Kaplan Meier method. Differences in time to death between patient groups were estimated using Cox proportional hazards models. Non-relapse mortality was estimated using Fine and GrayÕs method.Results: Between 2005 and 2014, 40 patients received a second BMT for a relapsed hematologic malignancy (Table 1). The median age at second transplant was 43.9 (range 1 to 74); 14 (35%) were female. Fifteen (41%) received myeloablative conditioning for their first transplant, and 35 (92%) received high dose post-transplant cyclophosphamide (PTCy) as part of their GVHD prophylaxis. The incidence of grade 2-4 aGVHD after the first transplant was 13%, and limited cGVHD was 13%. There was no extensive cGVHD.Re-induction therapy and second allograft characteristics (Table 2): Refractory or progressive disease at the time of second transplant was present in 20% of patients, and 7/40 (18%) had their second transplant within 1 year. After a first failed HLA-matched transplant, 15 received a haploidentical graft, and 4 received a second HLA-matched graft. Among the 21 who relapsed after a haploBMT, 7 received an HLA-matched allograft, and 14 received a haploidentical graft; 6 out of those 14 used a donor that switched the shared haplotype. Most (81%) received PTCy with the second BMT.Median follow up is 598 days. Median OS in the cohort is 911 days (95% CI 602 Ð NR); 4 year OS is 38%. The CI of NRM by 2 years was 29% - 4 patients died of complications of GVHD (only one of whom received post-transplant Cyclophosphamide), 3 associated with prolonged cytopenias, 1 within a month of BMT, and 3 of pneumonia. Grade 2-4 aGVHD occurred in 11 pts (28%), grade 3-4 in 5 (13%). Extensive cGVHD was seen in 7 (18%).Median OS for the patients who relapsed after initial haploBMT who were then retransplanted with an HLA-haploidentical donor with a different shared haplotype has not been reached, versus a median OS of 501 [317-2950+] days among the 15 who did not receive a graft with an alternate shared haplotype (HR 0.21 [0.03, 1.61]; p=0.06). If the 19 patients who received a matched allograft at first transplant are included, median OS is 552 days in the group transplanted with a second graft with the same shared haplotype(s), and 1308 days (Figure 1) in the group whose allograft contained a different non-shared haplotype (HR 0.39 [0.16, 0.98]; p=0.04).OS was better when the second transplant was performed more than one year after the first (HR 0.30 [0.11, 0.80]; p=0.03). A trend towards improved OS was associated with disease status at time of second transplant (remission or chemo-responsiveness versus progressive or refractory disease; HR 0.41 [0.16, 1.03]; p=0.07). Source of graft (BM versus peripheral), conditioning intensity, era of transplant (2005-2010 versus 2010-2015), same versus different donor, and age group (<25, 25-60, 60+) did not significantly influence OS.Conclusion: Second transplants are feasible in all age groups and provide a reasonable chance of long-term survival. GVHD rates using PTCy are low, and similar to that seen with first BMTs. An allograft sharing a different haplotype in the case of relapse after haploBMT, or a haploidentical donor after failure of a matched graft, may be beneficial. [Display omitted] [Display omitted] [Display omitted] DisclosuresBrodsky:Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Achillion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Cytomegalovirus Reactivation Does Not Increase Subsequent Risk for Acute Graft-Versus-Host Disease, Malignant Disease Relapse, or Infection Following Allogeneic Hematopoietic Cell Transplantation

Background: Identifying factors that influence donor-derived immune response may ultimately enable its therapeutic redirection, lessening risk for complications following allogeneic hematopoietic cell transplantation (alloHCT) like acute graft-versus-host disease (aGvHD) and promoting protection against infection and malignant disease relapse. Viral reactivation seems poised to influence donor-derived immune response, potentially disrupting the balance between immune surveillance in eradicating malignancy and infection and immune tolerance in preventing aGvHD. Cytomegalovirus (CMV) is a clinically-significant virus with immunomodulatory capabilities. However, studies interrogating such effects are limited in the modern transplant era. The primary study aim was to estimate the cumulative incidence of initial CMV reactivation (RA) and aGvHD in alloHCT patients and to assess reciprocal influence between CMV RA and aGvHD. The secondary study aim was to define whether CMV RA predisposed alloHCT patients to infection or increased relapse risk.Methods: Consecutive adult patients (n=324) with acute lymphoblastic leukemia, acute myelogenous leukemia or myelodysplasia whom received initial matched sibling or unrelated donor (MUD) bone marrow (n=33), peripheral blood stem cell (PBSC, n=253) or umbilical cord blood (n=38) grafts from January 2010 through December 2014 at The Ohio State University Comprehensive Cancer Center comprised the study cohort. Patient-, transplant-, and infection-related data were retrospectively analyzed (Table 1). Initial CMV RA was defined as plasma quantitative CMV PCR≥1000 viral copies/ml for which CMV-directed antiviral therapy was started. Microbiologically-documented infections were recorded for the first year after alloHCT and categorized as bacterial blood stream infection, invasive fungal infection, human herpes virus 6 viremia, and respiratory viral infection.Cumulative incidences of CMV RA and aGvHD were estimated accounting for competing risks (death from any cause). Association between CMV RA and incidence of aGvHD was evaluated in a proportional sub-distribution hazards model, where CMV RA was treated as a time-dependent covariate with competing risk as death from any cause. Similarly, influence of aGvHD on incidence of CMV RA was evaluated where development of aGvHD was treated as the time-dependent covariate and CMVR RA as the end point of interest. Associations between CMV RA and subsequent infection or disease relapse were similarly analyzed. To evaluate impact of CMV and aGvHD on long-term outcomes, landmark analysis (LMA) at D100 and D365 were compared among four distinct patient groups: (1) No CMV RA, no aGvHD; (2) CMV RA, no aGvHD; (3) No CMV RA, aGvHD; and (4) CMV RA and aGvHD.Results: Most transplant patients had AML in CR1, received MUD PBSC grafts following myeloablative conditioning, and were given methotrexate and calcineurin-based GvHD prophylaxis. Patients who developed aGvHD grades 2 (HR=1.93, 95% CI 1.15-3.23, p=0.013) or grades 3 and 4 (HR=3.36, 95% CI 1.76-6.45, p<0.001) had higher risk for developing subsequent CMV RA. In contrast, patients with initial CMV RA did not have increased risk for developing future aGvHD. Similarly, CMV RA did not have a significant impact on future infection, regardless of infection type, nor impact subsequent risk of malignant disease relapse.Overall survival (OS) at 1, 2, and 3 years post-transplant were 63%, 53%, and 45%, respectively. Cumulative incidence rates for non-relapse mortality (NRM) at 1, 2, and 3 years were 16%, 19%, and 23%, respectively; for infection-related mortality (IRM), cumulative incidence rates were 10%, 13%, and 16%, respectively. OS, NRM and IRM were stratified by initial CMV RA and aGvHD status at D100 and D365 (Table 2). Among patients who were alive, patients whom had initial CMV RA and aGvHD by D100 were at higher risk for NRM (HR=2.85, 95% CI 1.24-6.56, p=0.014) and IRM (HR=3.65, 95% CI 1.39-9.57, p=0.008) than patients who experienced neither CMV RA nor aGvHD. D365 LMA did not reveal any statistically significant differences in OS, NRM, and IRM between groups.Conclusion: aGvHD associated with increased risk for CMV RA, but initial CMV RA did not associate with subsequent aGvHD risk. Furthermore, initial CMV RA did not associate with increased risk for disease relapse or infection, but did increase NRM and IRM, particularly in combination with aGvHD. [Display omitted] [Display omitted] DisclosuresAuletta:Shire Pharmaceuticals: Consultancy. Lozanski:Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding; Beckman Coulter: Research Funding. Hofmeister:Janssen: Pharmaceutical Companies of Johnson & Johnson: Research Funding; Karyopharm Therapeutics: Research Funding; Signal Genetics, Inc.: Membership on an entity’s Board of Directors or advisory committees; Incyte, Corp: Membership on an entity’s Board of Directors or advisory committees; Celgene: Research Funding; Arno Therapeutics, Inc.: Research Funding; Takeda Pharmaceutical Company: Research Funding; Teva: Membership on an entity’s Board of Directors or advisory committees. Andritsos:Hairy Cell Leukemia Foundation: Research Funding.

Outcome disparities between African Americans and Caucasians in contemporary kidney transplant recipients

BackgroundRacial disparities in African-American (AA) kidney transplant have persisted for nearly 40 years, with limited data available on the scope of this issue in the contemporary era of transplantation. MethodsDescriptive retrospective cohort study of US registry data including adult solitary kidney transplants between Jan 1, 2005 to Dec 31, 2009. Results60,695 recipients were included; 41,426 Caucasians (68%) and 19,269 AAs (32%). At baseline, AAs were younger, had lower college graduation rates, were more likely to be receiving public health insurance and have diabetes. At one-year post-transplant, AAs had 62% higher risk of graft loss (RR 1.62, 95% CI 1.50–1.75) which increased to 93% at five years (RR 1.93, 95% CI 1.85–2.01). Adjusted risk of graft loss, accounting for baseline characteristics, was 60% higher in AAs (HR 1.61 [1.52–1.69]). AAs had significantly higher risk of acute rejection and delayed graft function. ConclusionAAs continue to experience disproportionately high rates of graft loss within the contemporary era of transplant, which are related to a convergence of an array of socioeconomic and biologic risk factors.

Improved Access to Lung Transplantation Among Adolescents After Introduction of the Lung Allocation Score

SESSION TITLE: Pediatric Pulmonary SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 25, 2016 at 02:45 PM - 04:15 PM PURPOSE: The Lung Allocation Score (LAS) was introduced in May 2005 to allocate donor lungs to lung transplant (LTx) candidates ages 12 years and older on the basis of transplant urgency, while lung allocation for patients <12 years old remained dependent on waiting time. Effects of LAS implementation on outcomes in pediatric LTx candidates are unclear. METHODS: The United Network for Organ Sharing registry was queried to identify first-time LTx candidates ages 0-17 years listed between 1995-2015. Waitlist outcomes included transplantation, mortality, and removal due to deteriorating condition. One-year survival was assessed post-transplant. Difference-in-difference models were fitted to estimate the influence of LAS implementation on outcomes of adolescents (ages 12-17) compared to children (ages 0-11). Competing-risks regression was used for waitlist outcomes and Cox proportional hazards regression was used for 1-year post-transplant survival. Trends in the LAS among adolescents listed after LAS implementation were described using least-squares regression. RESULTS: There were 1,287 adolescents (495 listed after LAS implementation) and 981 children (370 listed after LAS implementation) who were listed for LTx since 1995 and selected for analysis. The most common waitlist outcome was transplantation (47% of adolescents and 45% of children), whereas 17% of children and 16% of adolescents died on the waitlist. In competing-risks regression, LAS implementation increased the hazard of transplantation for adolescent candidates (HR=2.21; 95% CI=1.89, 2.58; p<0.001), and the interaction between adolescent age and transplant era determined this improvement was greater for adolescents than for children (p<0.001). There was no significant change in waitlist mortality hazard among adolescents when comparing the LAS to the pre-LAS era (HR=0.79; 95% CI=0.59, 1.06; p=0.119). Among LTx recipients (593 adolescents, 435 children), Cox analysis of 1-year mortality demonstrated marginally significant improvement in survival for adolescents after LAS implementation (HR=0.68; 95% CI=0.46, 1.03; p=0.066), and no significant difference in this effect between children and adolescents (p=0.596). Since LAS implementation, adolescents’ LAS at transplantation has trended upwards by 0.78 points (95% CI=0.09, 1.46; p=0.027) each year. CONCLUSIONS: Relative to children <12 years old, LAS implementation improved access to LTx for adolescents ages 12-17, although LAS-era improvements in post-transplant outcomes among adolescents were modest. The latter may be attributable to a trend towards transplanting adolescents with higher transplant urgency in the recent era. CLINICAL IMPLICATIONS: Donor allocation for LTx in children remains to be a controversial topic in the United States. The LAS system appears to have made a positive impact on LTx in adolescent candidates since implementation. DISCLOSURE: The following authors have nothing to disclose: Don Hayes, Jr., Joseph Tobias, Dmitry Tumin No Product/Research Disclosure Information

Rizikos veiksniai, lemiantys ilgalaikį transplantuoto inksto išgyvenimą: LSMU Kauno klinikų 13 metų inkstų transplantacijos patirtis

Augant inksto transplantacijų skaičiui ir siekiant pagerinti transplantacijos baigtis, ieškoma veiksnių, kurie galėtų sąlygoti ilgalaikį transplantuoto inksto išgyvenimą. Tiek donoro, tiek recipiento veiksniai, tiek jų sąveika gali nulemti transplantacijos baigtis. Šiuo retrospektyviu tyrimu siekėme išanalizuoti mūsų centro transplantuotų pacientų populiacijos rezultatus bei įvertinti rizikos veiksnius, susijusius su blogesniu transplantuoto inksto išgyvenimu. Išanalizuoti 277 inksto recipientų duomenys, kuriems inksto persodinimo operacija atlikta 2000 - 2013 metais Lietuvos sveikatos mokslų universiteto Kauno klinikose (LSMUKK). Demografiniai ir klinikiniai duomenys palyginti su pirmųjų dešimties metų inkstų transplantacijų LSMUKK rezultatais, kurie jau buvo publikuoti [1]. Iš visos transplantuotų pacientų populiacijos atrinkti pacientai, kurie išvyko iš stacionaro su veikiančiu inkstu ir pagal transplantuoto inksto išgyvenimą suskirstyti į dvi grupes: I grupė – recipientai, kurių inkstas veikė ≥ 5 metus (n=100); II grupė – recipientai, kurių inkstas veikė &amp;lt; 5 metus (n=25). Bendras visos LSMUKK transplantuotų populiacijos (n=277) inksto išgyvenimas po 1, 3, 5, 7 ir 10 m. - 86,6 proc., 79,5 proc., 72,4 proc., 66,1 proc. ir 58,3 proc., atitinkamai, o neįtraukus mirusių su veikiančiu transplantuotu inkstu - po 1, 3, 5, 7 ir 10 m. - 89,6 proc., 85,6 proc., 80,4 proc., 78,7 proc., 76,0 proc. atitinkamai. Lyginant grupes vienveiksnės logistinės analizės būdu nustatyti faktoriai, sąlygojantys blogesnį ilgalaikį transplantuoto inksto išgyvenimą - donoro amžius, recipiento hipertenzijos anamnezė, didesnis nesutapimų pagal HLA sistemą skaičius bei pavėluota transplantuoto inksto funkcija, t.y. dializės poreikis po transplantacijos. Sudarytas daugiaveiksnės logistinės analizės modelis, kuriuo remiantis nustatyta, kad statistiškai reikšmingai trumpesnis nei 5 m. transplantuoto inksto išgyvenimas tikėtinas esant vyresniam nei 40 m. amžiaus donorui (ŠS 3,387, p=0,021), pavėluotai transplantuoto inksto funkcijai (ŠS 3,426, p=0,015) ir didesniam nei 3 nesutapimų skaičiui pagal HLA sistemą (ŠS 2,919, p=0,036). Mūsų tyrimas parodė, kad jaunesnis donoro amžius, gera ankstyva transplantuoto inksto funkcija bei tikslesnis imunologinis sutapimas yra svarbūs veiksniai transplantuoto inksto ilgalaikiam išgyvenimui. Visa tai nurodo, kad kruopšti donorų atranka, pooperacinė priežiūra ir imunosupresinio gydymo protokolų individualizavimas yra svarbus transplantacijos procese.

La transplantation rénale en 2046 : avenir et perspectives

To report major findings that may build the future of kidney transplantation. Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) database from 1960to 2016using the following keywords, in association, "bio-engineering; heterotransplantation; immunomodulation; kidney; regenerative medicine; xenotransplantation". Articles were selected according to methods, language of publication and relevance. A total of 5621articles were identified including 2264for xenotransplantation, 1058for regenerative medicine and 2299for immunomodulation; after careful selection, 86publications were eligible for our review. Despite genetic constructs, xenotransplantation faces the inevitable obstacle of species barrier. Uncertainty regarding xenograft acceptance by recipients as well as ethical considerations due to the debatable utilization of animal lives, are major limits for its future. Regenerative medicine and tridimensional bioprinting allow successful implantation of organs. Bioengineering, using decellularized tissue matrices or synthetic scaffold, seeded with pluripotent cells and assembled using bioreactors, provide exciting results but remain far for reconstituting renal complexity and vascular patency. Immune tolerance may be achieved through a tough initial T-cell depletion or a combined haplo-identical bone marrow transplant leading to lymphohematopoietic chimerism. Current researches aim to increase the pool of organs available for transplantation (xenotransplants and bio-artificial kidneys) and to increase allograft survival through the induction of immune tolerance. Reported results suggest the onset of a thrilling new era for renal transplantation providing end-stage renal disease-patients with an improved survival and quality of life.

An Exciting New Era in Donor Organ Preservation and Transplantation: Assess, Condition, and Repair!

An Exciting New Era in Donor Organ Preservation and Transplantation: Assess, Condition, and Repair!

The Registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Heart Transplantation Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant

The Registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Heart Transplantation Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant

Sixty as the new forty: considerations on older related stem cell donors.

The era of reduced-intensity allogeneic stem cell transplantation, with its emphasis on older patients, has created new challenges in the management of what is now an older related stem cell donor population. These donors are now on average no less than 10 years older than in the mid-1990s. Donors over 70 years of age are no longer isolated or exceptional cases. They may still be considered eligible for donation but many of them, based on the older age and their medical history, may no longer fully qualify as 'healthy' or 'normal'. The older the donor, the more likely that hematologic abnormalities, comorbidities and treated malignancies will complicate the picture. Assessing the risk-benefit ratio for both donor and recipient can now be more challenging than ever.

329 - Outcomes of Older Patients in the Recent Era of Heart Kidney Transplantation

329 - Outcomes of Older Patients in the Recent Era of Heart Kidney Transplantation

351 - Contemporary Era of Simultaneous Heart Kidney Transplantation: A Single Center Experience

Background: Despite increasingly sicker patients and changes in perioperative techniques, the contemporary era of simultaneous heart kidney transplantation (HKT) has not been well described. We report intraoperative characteristics, postoperative medical management and causes of death in patients undergoing HKT at a single center. Methods: Patients undergoing HKT between 2009 and 2015 at Temple University Hospital were identified through review of the electronic medical record and the UNOS registry. Demographics, cause of cardiomyopathy and renal failure, comorbidities and need for preoperative dialysis, mechanical circulatory support (MCS) and inotropes were identified. Cardiac allograft ischemic time and type of immunosuppression therapy were collected. Incidence of treated rejection and death was measured. Results: Six patients underwent HKT, with average age of 61.7 ± 9.1 years. Four were male. Causes of cardiomyopathy included transplant vasculopathy (n = 3), ischemic cardiomyopathy (n = 2) and non ischemic cardiomyopathy (n = 1). Overlapping causes of renal failure were identified, including the cardiorenal syndrome (n = 3), diabetic nephropathy (n = 1), drug toxicity (one calcineurin, one vancomycin), and acute tubular necrosis (n = 2). Prior to HKT, two patients required inotropes, two MCS and two dialysis. All patients received induction immunosuppression (two basiliximab and four alemtuzumab). Average cardiac allograft ischemic and pump times were 157.6 ± 35.5 min and 185.6 ± 58.5 min respectively. One patient was treated for cardiac rejection and one for kidney rejection within the first year. One was initiated on dialysis more than 5 years after HKT. Two patients died within the first year due to sepsis and multiorgan failure. The remaining four were alive at the last clinic visit, median 801 days after HKT. Conclusions: At our center, most patients undergoing HKT required advanced hemodynamic support, with either MCS or inotropes. Causes of cardiomyopathy and renal failure were varied. One year mortality remains high in the first year after transplant and appears related to infectious complications in this sick population. Further research is required to delineate the ideal perioperative strategy regarding immunosuppression and Intraoperative management.

367 - Post-Heart Transplant Mortality Rates Did Not Improve Amongst Extra-Corporeal Membrane Oxygenation Supported Adults in Contemporary Transplant Era

367 - Post-Heart Transplant Mortality Rates Did Not Improve Amongst Extra-Corporeal Membrane Oxygenation Supported Adults in Contemporary Transplant Era

Management of Crohn's Disease in the New Era of Gut Rehabilitation and Intestinal Transplantation.

Despite recent therapeutic advances, patients with Crohn's disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.

Current state of ex-vivo lung perfusion.

The purpose of the current report is to review the ex-vivo peer-reviewed literature published in the last 5 years and to summarize the findings. Encouraging data have been published by several centers utilizing ex-vivo lung perfusion (EVLP) as a means to identify viable grafts from the high-risk donor pool. The outcomes of transplanted lungs that were initially declined because of poor quality, but reevaluated with ex-vivo perfusion, are equivalent to standard criteria donor lungs. Further, research reports have emphasized the role of ex-vivo perfusion as a platform to improve graft quality and reduce the injurious effects of ischemia-reperfusion. Over the last 10 years, EVLP has proved its value as a reassessment tool to increase donor utilization. As short- and long-term data demonstrate the safety of EVLP, its use as a therapeutic platform is emerging, along with the promise of a new era in lung transplantation.

Efficacy and safety of antibody induction therapy in the current era of kidney transplantation.

Antibody induction with polyclonal rabbit-antithymocyte globulin (rATG) or an interleukin-2 receptor antagonist (IL-2RA) is widely used in kidney transplantation. Collaborative Transplant Study data from 38 311 first deceased-donor kidney transplants (2004-13) were analysed. Transplants were classified as 'normal risk' or 'increased risk' according to current guidelines. Cox regression analysis was applied to subpopulations of propensity score-matched recipients. rATG or IL-2RA induction was given to 64% of increased-risk and 53% of normal-risk patients, respectively. rATG and IL-2RA induction were each associated with reduced risk for graft loss versus no induction in increased-risk patients [hazard ratio (HR) 0.85, P = 0.046 and HR 0.89, P = 0.011, respectively]. The HR values for incidence of treated rejection in increased-risk patients for rATG and IL-2RA versus no induction were 0.75 (P = 0.037) and 0.77 (P < 0.001), respectively. In the normal risk subpopulation, neither induction therapy significantly affected the risk of graft loss or treated rejection. Hospitalization for infection was increased by rATG (P < 0.001) and IL-2RA (P < 0.001) induction. In contrast to patients transplanted during 1994-2003, among patients transplanted during 2004-13, rATG did not significantly affect the risk of non-Hodgkin's lymphoma versus no induction (P = 0.68). Induction therapy following kidney transplantation should be targeted to increased-risk transplants. In this analysis, a beneficial effect of antibody induction in normal-risk transplants could not be demonstrated.

Early renal function recovery and long-term graft survival in kidney transplantation.

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P=0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx.

Outcomes in Patients Bridged With Univentricular and Biventricular Devices in the Modern Era of Heart Transplantation

Biventricular support before orthotopic heart transplantation (OHT) has been shown to adversely affect short- and long-term outcomes, but the comparative effect of support type is largely unknown. This study determined the comparative effect of univentricular and biventricular support on survival in bridged patients after OHT. The United Network of Organ Sharing database was queried for adult patients bridged to OHT with a univentricular (left ventricular assist device [LVAD]), biventricular (biventricular assist device [BiVAD]), or total artificial heart ([TAH]) device between 2004 and 2012. Unconditional and conditional survivals were compared with the Kaplan-Meier method. Cox proportional hazards regression models were constructed to determine the risk-adjusted influence of support type on death. Of the 4,177 patients identified, 3,457 (20.4%), 575 (3.4%), and 145 (0.9%) were bridged with anLVAD, BiVAD, and TAH, respectively. Unadjusted 30-day, 1-year, and 5-year estimated survival was greater in LVAD patients than in the BiVAD and TAH cohorts. After risk-adjustment, BiVAD and TAH were associated with an increased risk of death at all time points. Unadjustedand adjusted 5-year survival, conditional on 1-year survival, was worse, however, in only TAH patients. Patients with biventricular failure bridged to OHT with a TAH or BiVAD experience worse short- and long-term survival comparison with those withan LVAD. This difference is most likely due to an increase in early death and depends on the type of BiVAD device implanted.

(259) - A Novel Donor Risk Scoring System to Predict 1-Year Mortality in Pediatric Heart Transplantation

s S103 3 (n = 4/48 (8.3%); p = 0.02), and most recent era of transplantation (2006-2014) (n = 92/2544 (3.6%); p < 0.0001). Donor and recipient age, donor echo function and ischemic time were all not predictive of MCS. In a logistic multivariable regression analysis, factors predicting MCS within 30 days were more recent era (O.R. 1.43 (1.31 1.56), p < 0.0001) and CHD (O.R. 2.06 (1.33 3.17), p = 0.001). Conclusion: MCS has historically been uncommon following pediatric heart transplant, although it is becoming more widely used, particularly early posttransplant. Patients with a diagnosis of congenital heart disease were twice as likely to need MCS early post-transplant compared to those with cardiomyopathy. Need for MCS later post-transplant was associated with a greater need for re-transplant.

Reappraisal of the Role of Portacaval Shunting in the Growth of Patients With Glycogen Storage Disease Type I in the Era of Liver Transplantation

Instead of dietary modification, surgical management is considered for correcting growth retardation, poor metabolic control, and hepatocellular adenoma (HCA) in glycogen storage disease (GSD) type I. The records of 55 GSD type I patients were retrospectively reviewed. Thirty-two patients underwent only dietary management (group D) and 23 underwent surgical management (group S). In group S, 17 underwent portacaval shunting (PCS), 13 underwent liver transplantation (LT; 7 underwent both PCS and LT). Height-for-age and body mass index-for-age Z-scores based on World Health Organization data were used to compare growth patterns before and after surgery. Changes in metabolic abnormalities and HCA after operation were also investigated. Height-for-age Z-scores for group S were higher by an average of 0.377 compared to that for group D. Metabolic abnormalities often disappeared after LT but improved partially after PCS. De novo HCA was detected in 4 patients (13%) from group D, 12 (100%) who underwent PCS, and none who underwent LT. One case of hepatocellular carcinoma and one of hemorrhage from a HCA were noted in group D. Two cases of hepatocellular carcinoma, 2 of hemorrhage, and 1 of necrosis were noted after PCS. Surgery yielded greater growth improvement than dietary management. However, after PCS, metabolic abnormalities remained unresolved, and the de novo HCA rate was high. Portacaval shunting can be used to improve growth in GSD type I patients when LT is not possible, but close observation for metabolic abnormalities and HCA is essential.