Emerging role of myeloid-derived suppressor cells in the biology of transplantation tolerance MDSCs, a heterogeneous population of myeloid cells, are characterized by their immunosuppressive abilities through the secretion of various cytokines such as iNOS, NO, ROS, TGF-β, and Arg-1. Accumulating evidence highlights its potential role in maintaining immune tolerance in solid organ and hematopoietic stem cell transplantation (HSCT). Mechanistically, MDSCs induced transplant tolerance is mainly dependent on direct suppression of allogeneic reaction or strengthened crosstalk between MDSCs and Treg or NKT cells. Adopted transfer of in vitro- or in vivo-induced MDSCs by special drugs therefore becomes a potential strategy for maintaining transplantation tolerance. In this review, we will summarize the previously published data regarding the role of MDSCs in the biology of transplantation tolerance and gain insights into the possible molecular mechanism governing this process. Disclosure The authors declare that they have no conflict of interest. Funding This paper is supported by National Natural Science Foundation of China (No.81500151 & 81160074), Natural Science Foundation of Hubei Province (No.2017CFB631) and Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund (No.znpy2018025). Correspondence information: Dr. Liang Shao, Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China. E-mail: liangsmd@163.com Tel:+86 15871455000 Prof. Albert KW Lie, Division of Hematology & BMT Center, Queen Mary Hospital, Hong Kong, SAR China. E-mail: akwlie@hku.hk, Tel:+852 22555859, Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Safety of donation from brain-dead organ donors with central nervous system tumors: Analysis of transplantation outcomes in Korea Background: This study aims to verify the condition of recipients of solid organs from donors with central nervous system (CNS) tumors and determine the risk of disease transmission due to transplantation. Methods: Twenty-eight brain-dead organ donors with CNS tumors and 91 recipients who received solid organs from January 1, 2005, to December 31, 2014, in Korea were investigated using the Korean Network of Organ Sharing data. Results: Of the 36 recipients of organs from the 11 donors whose pathological results were not verified, four developed tumors: renal cell carcinoma, carcinoma in situ of the cervix uteri, B-cell lymphoma, and colon cancer. Among 51 recipients from 17 donors with CNS tumor, no recipient had the same tumor as the donors. Six were classified as high-risk donors according to the World Health Organization (WHO) classification, and 14 recipients from these donors did not develop tumor after transplantation. The remaining 11 donors were classified as low-risk donors according to the WHO classification but as high-risk donors according to the Malignancy Subcommittee of the Disease Transmission Advisory Committee of the Organ Procurement and Transplantation Network/United Network for Organ Sharing. Of the 37 recipients, three had recurring hepatocellular carcinoma with lung and bone metastases, thyroid cancer, and Kaposi’s sarcoma after transplantation. Conclusions: The risk of disease transmission due to organ transplantation from donors with CNS tumors was very low. Thus, organ donation from such donors should be promoted actively to expand the donor range. Funding: None Disclosure: The authors declare no conflicts of interest. Address for correspondence: Jae-myeong Lee, MD, PhD, Department of Acute Care Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, Seoul, Republic of Korea. Tel: +82-2-920-5948, Fax: +82-2-920-5948, E-mail: ljm3225@hanmail.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Donors with central nervous system cancer: Proceed with vigilance No abstract available

Anti-BAFF therapy: a new tool to target B cells in antibody-mediated rejection? No abstract available

Circulating donor-derived cell-free DNA as a biomarker in vascularized composite allotransplantation? No abstract available

Shorter Height is Associated with Lower Probability of Liver Transplantation in Patients with Hepatocellular Carcinoma Background: The effect of height and sex on liver transplantation (LT) for hepatocellular carcinoma (HCC) remains unclear. Methods: Using United Network for Organ Sharing (UNOS) data, 14,844 HCC patients listed for LT from 2005-2015 were identified. Cumulative incidence of waitlist events (LT and dropout for death or too sick) were calculated and modeled using Fine and Gray competing risk regression. Results: Short (SWR), Mid (MWR) and Long (LWR) UNOS wait regions comprised 25%, 42%, and 33% of the cohort. Three-year cumulative incidence of LT was lower in shorter height patients (≤150, 151-165, and >185 cm; 70.8%, 76.7%, and 83.5%, p<0.001) and women (78.2% vs 79.8%, p<0.001) and. On multivariable analysis, shorter height (≤150, 151-165 cm, HR versus >185 cm) was associated with lower probability of LT (0.81 and 0.89, p=0.02) and greater dropout (HR 1.99 and 1.43, p<0.001). Female sex was not associated with LT overall, but a significant sex and wait region interaction (p=0.006) identified lower LT probability for women in MWR (HR versus men, 0.91, p=0.02). Conclusion: Despite uniform HCC MELD exception across height and sex, shorter patients and females in MWR have lower probability of LT. Consideration should be given to awarding additional MELD exception points to these patients. Disclosures: None of the authors have any relevant potential conflicts of interest to disclose Financial Support: This work was supported by the Clinical and Translational Core of the UCSF Liver Center (P30 DK026473). Corresponding Author: Neil Mehta, M.D., University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0538, E-mail: neil.mehta@ucsf.edu Tel: (415)-476-2777, Fax: (415)-476-0659 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Randomized Sirolimus-based early calcineurin inhibitor reduction in liver transplantation: impact on renal function Background. The long-term use of calcineurin inhibitors (CNI) after liver transplantation (LT) is associated with nephrotoxicity. Methods. 5-year follow-up data was retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mTOR-free immunosuppression (group A, n=264) was compared to a 50 % reduction of CNI and introduction of the mTOR inhibitor Sirolimus within 4 to 6 weeks after LT (group B, n=261). Results. Median MELD at LT was low with 10 (7 - 15) (group A) and 11 (8 - 15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months post transplantation. Renal function was preserved at 3 months after LT in the Sirolimus arm [eGFR 74 (57-95) versus 67 (55-85) ml/min/1.73m2, p=0.004] but was similarly impaired thereafter compared to group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and Sirolimus treatment ≥ year 1 with significantly superior eGFR and lowest rate of chronic kidney disease (≥ stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder and hyperglycemia) were not associated with worse kidney function. Conclusions. Prevention of CNI nephrotoxicity by Sirolimus-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and Sirolimus maintenance achieved better long-term renal outcomes compared to real-world practice. * The SiLVER study investigators that are not authors of this work are listed under Acknowledgments. Clinical Trial Number EudraCT: 2005-005362-36; Clinicaltrials.gov: NCT00355862 Funding: This investigator initiated trial (SiLVER) was supported by a research grant from Pfizer Inc. to EKG and sponsored by the University Hospital Regensburg, Germany. Disclosure: EKG has received speaking fees from Novartis. AAS received travel support from Pfizer. BMB, JWF, PN, HJS and DFM declare no conflict of interest. Correspondence/Reprints: Prof. Darius F Mirza, Consultant Liver Transplant Surgeon, Liver Unit, Queen Elizabeth Hospital Birmingham and Birmingham Childrens’ Hospital, Mindelsohn Way, Birmingham, United Kingdom B15 2TH., Phone +44 (121) 697-8391, Email: Darius.Mirza@uhb.nhs.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A case of hidroacanthoma simplex in a cardiac transplant recipient No abstract available

Posttransplant outcomes for cPRA-100% recipients under the new Kidney Allocation System Background: There is concern in the transplant community that outcomes for the most highly sensitized recipients might be poor under KAS high-prioritization. Methods: To study this, we compared posttransplant outcomes of 525 pre-KAS (12/4/2009-12/3/2014) cPRA-100% recipients to 3026 post-KAS (12/4/2014-12/3/2017) cPRA-100% recipients using SRTR data. We compared mortality and death-censored graft survival using Cox regression, acute rejection and delayed graft function (DGF) using logistic regression, and length of stay (LOS) using negative binomial regression. Results: Compared to pre-KAS recipients, post-KAS recipients were allocated kidneys with lower KDPI (median 30% vs. 35%, p<0.001) but longer cold ischemic time (median 21.0 hours vs. 18.6, p<0.001). Compared to pre-KAS cPRA-100% recipients, those post-KAS had higher 3-year patient survival (93.6% vs. 91.4%, p=0.04) and 3-year death-censored graft survival (93.7% vs. 90.6%, p=0.005). The incidence of DGF (29.3%vs. 29.2%, p=0.9), acute rejection (11.2% vs. 11.7%, p=0.8), and median LOS (5 days vs. 5, p=0.2) were similar between pre-KAS and post-KAS recipients. After accounting for secular trends and adjusting for recipient characteristics, post-KAS recipients had no difference in mortality (adjusted hazard ratio [aHR]: 0.861.623.06, p=0.1), death-censored graft failure (aHR: 0.521.001.91, p>0.9), DGF (adjusted odds ratio [aOR]: 0.580.861.27, p=0.4), acute rejection (aOR: 0.610.941.43, p=0.8), and LOS (adjusted LOS ratio: 0.981.161.36, p=0.08). Conclusion: We did not find any statistically significant worsening of outcomes for cPRA-100% recipients under KAS, although longer-term monitoring of posttransplant mortality is warranted. DISCLOSURES:The authors of this manuscript have no conflicts of interest to disclose as described by Transplantation FUNDING:This work was supported by grant numbers F32DK113719 (Jackson), F32DK109662 (Holscher), K01DK101677 (Massie), K23DK115908 (Garonzik-Wang), and K24DK101828 (Segev) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dr. Holscher is supported by the American College of Surgeons Resident Research Scholarship. Correspondence: Dorry Segev, M.D., Ph.D., Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology, Associate Vice Chair, Department of Surgery, Director, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University, 2000 E Monument St., Baltimore, MD 21205, 410-502-6115 (tel) 410-614-2079 (fax), dorry@jhmi.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Liver transplantation for hepatic epithelioid hemangioendothelioma is facilitated by exception points with acceptable long-term outcomes Background: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with a high mortality rate. HEHE is now a formally recognized indication for exception point priority in the U.S. under the new National Liver Review Board. The role of liver transplantation (LT) and exception point waitlist priority in the U.S. for patients with HEHE remains understudied. Methods: This was a retrospective cohort study using the United Network for Organ Sharing transplant database. From 2/27/02-1/31/18, 131 adults waitlisted for LT with HEHE were identified by free-text entry. Results: Exception point applications were submitted for 91.6% (120/131) of patients. All patients with fully reviewed applications received exception points at least once during waitlisting, and 85% (103/120) upon first submission. Among the 88 patients transplanted, median Model for End-stage Liver Disease (MELD) score at LT was 7 (IQR: 6-11) and waiting time 78.5 days [IQR: 29.5-237.5]. Unadjusted post-LT survival of HEHE recipients at 1-, 3- and 5-years from LT was 88.6%, 78.9% and 77.2%. Unadjusted post-LT patient and graft survival of HEHE patients was not different from patients with hepatocellular carcinoma within Milan receiving exception point priority (p=0.08). An increased rate of graft failure due to hepatic artery thrombosis ≤14 days from initial LT was observed in HEHE versus non-HEHE patients (4.6% vs 0.5%). Conclusions: The majority of HEHE recipients receive exception points at a universal approval rate allowing prompt access to deceased donor LT. Disclosure: The authors declare no actual or potential conflicts of interest for this study. Funding: This study received no external funding. Correspondence Information: Therese Bittermann, MD, MSCE, Hospital of the University of Pennsylvania, Penn Transplant Institute, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, Email: therese.bittermann@pennmedicine.upenn.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.