Acknowledgement to Reviewers of OBM Transplantation in 2021

The editors of OBM Transplantation would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2021. We greatly appreciate the contribution of expert reviewers, which is crucial to the journal's editorial process. We aim to recognize reviewer contributions through several mechanisms, of which the annual publication of reviewer names is one. Reviewers receive a voucher entitling them to a discount on their next LIDSEN publication and can download a certificate of recognition directly from our submission system. Additionally, reviewers can sign up to the service Publons (https://publons.com) to receive recognition. Of course, in these initiatives we are careful not to compromise reviewer confidentiality. Many reviewers see their work as a voluntary and often unseen part of their role as researchers. We are grateful to the time reviewers donate to our journals and the contribution they make.

The Donor – Recipient Weight Ratio is a Reliable Marker for Cell Yield in Hematopoietic Stem Cell Donations

Bone marrow transplants remain an import source of hematopoietic stem cells for patients suffering from specific diseases like aplastic anemia, for pediatric patients with malignant and non-malignant blood cell disorders, and for situations in which graft-versus-host disease (GvHD) is a concern. Identifying the optimal donor to achieve a 3-5 x 108/kg of recipient weight TNC yield may be challenging. In an analysis of 687 consecutive donors, donor and procedure characteristics were related to TNC/kg of recipient weight using Spearman correlation coefficients as well as linear and multiple regression analysis. We found correlations between donor WBC (r = 0.17), donor platelet counts (r = 0.15), donor BMI (r = 0.10), and the percentage of donor estimated blood volume accessed for harvesting (r = -0.57) with TNC/kg of recipient weight. The strongest correlation existed between the donor-recipient weight ratio and the TNC/kg (r = 84). In a multivariate regression analysis, the donor-recipient weight ratio influenced the TNC/kg of recipient weight more significantly (adjusted R2 = 0.84) than all other related variables put together. The minimal donor-recipient weight ratio associated with a TNC/kg of at least 3x108/kg of recipient weight was 0.8 (mean 3.425; 95% CI 2.01, 5.8). Using this donor-recipient ratio provides national bone marrow donor registries with a practical and simple measure to assure optimal cell yield outcomes in hematopoietic stem cell donations.

Economic Considerations in Using HCV and HIV Positive Donors for Kidney Transplant

End Stage Renal Disease is becoming more prevalent in the United States of America, with demand for kidney transplant exceeding the available organ supply. A novel method to increase the donor pool has been to consider transplanting organs from deceased patients who have had Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) infections. Transplants with HCV infected kidneys are becoming more prevalent, due to increased organ supply due to increased mortality from injection opioid use. Similarly, deceased donor transplants using kidneys infected with HIV have become more common following the passage of the “HIV Organ Policy Equity (HOPE) Act” in 2013. These novel transplant strategies present distinct socioeconomic impacts which differ from those of prior transplant practices. Here, we have reviewed the costs and benefits of receiving a kidney transplant from deceased donors infected with HIV or HCV, compared to receiving a non-viremic kidney transplant.

Experience with Alpha-1 Proteinase Replacement Post-Lung Transplantation in Alpha-1 Antitrypsin Deficiency: A Single Center Case Series

Alpha-1 antitrypsin deficiency (AATD) accounts for approximately 5% of lung transplants (LTx) performed annually. No studies have addressed the potential benefit of ongoing alpha-1 proteinase inhibitor (A1-PI) replacement to AATD patients post-LTx. Our primary objective was to assess potential benefits of continually administering A1-PI from pre- to post-transplantation for AATD LTx recipients. A retrospective case series was performed on AATD LTx recipients between 2002 and 2018. Data reviewed included date of A1-PI initiation, pulmonary function tests, and surveillance bronchoscopies. Endpoints included the change of forced expiratory volume in one-second (FEV1), infective episodes, chronic lung allograft dysfunction (CLAD), and acute rejection episodes. Out of the 13 AATD LTx recipients, 6 continually received A1-PI beginning prior to transplant (Group 1), and 7 were re-introduced to Α1-PI a number of years after LTx (Group 2). After two years, Group 1 experienced a median FEV1% predicted decline of 0.0%, and Group 2 experienced a median decline of 15.0%. No differences noted in frequency of infective episodes. One patient in Group 1 developed CLAD about 2.5 years post-LTx, whereas all Group 2 patients developed CLAD at a mean of 5.4 years post-LTx. No Group 1 patients experienced acute lung rejection episodes noted from surveillance bronchoscopies, corresponding data not available for Group 2. We report that the continual use of Α1-PI in AATD LTx recipients is associated with better maintenance and stabilization of lung function and potentially less acute lung rejection episodes early post-LTx. Prospective studies should be performed to confirm possible benefits.

Belatacept dosing in Lung Transplantation: is there a Method to the Madness?

Data supporting the use of belatacept in non-abdominal organs are limited to case series and small cohorts involving patients requiring conversion due to CNI intolerance or contraindication. Review articles summarizing the efficacy of belatacept salvage therapy in lung transplantation have previously been published, however, dosing regimens are highly variable and uniform guidance is lacking. In this article, indications and considerations for belatacept use in lung transplant recipients are reviewed with a specific focus on dosing regimens. Utilization of standardized dosing protocols to guide belatacept conversion will both improve the ability to directly assess outcomes and provide the opportunity to improve future patient care. A suggested framework for dosing selection and timeline for cross titration is proposed herein.

Defining Clinically Pathogenic HLA-Specific Antibodies - Granular Details in Characteristics in Pre and Early Time Following HLA-Antibody Incompatible Kidney Transplantation

Antibodies against donor HLA determine access to solid organ transplantation and in many cases the outcome of transplantation, but graft failure is not an inevitable consequence of their presence. Much research has been performed with two main aims – which antibodies represent the highest risk factor prior to transplantation, and second to understand how donor specific HLA antibodies behave after transplantation, with a long-term aim of being able to manipulate their production. HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity. Integral to the understanding of the large datasets generated is sophisticated mathematical analysis using techniques such as decision tree analysis and unsupervised machine learning. This review examines key aspects of this work, performed by us and others.

Efficacy of Autologous Stem Cell Transplantation for the Treatment of Multiple Myeloma in HIV-Positive Patients

Prior to the advent of anti-retroviral therapy (ART), autologous stem cell transplant (ASCT) was relatively contraindicated for multiple myeloma (MM) patients with human immunodeficiency virus (HIV) due to issues associated with stem cell harvest and the risk of opportunistic infections. With the widespread use of ART for control of HIV, ASCT is now the preferred treatment for relapsed lymphoma, the leading hematopoietic malignancy associated with HIV/AIDS. Hence, MM patients with HIV controlled by ART may benefit equally from aggressive combination treatment of chemotherapy and ASCT. This study seeks to evaluate the clinical course and treatment outcomes of patients with HIV and MM treated with ASCT. Five male patients with average age 53.2 years were included in this study. Patients were diagnosed with HIV prior to diagnosis of MM and were appropriately treated with ART prior to ASCT. All patients had undetectable HIV viral load (VL) prior to ASCT, and remained undetectable after ASCT. Adequate CD34+ stem cells were collected. Patients received high dose melphalan (200 mg/m2) followed by ASCT. ART was continued during ASCT. Patients experienced usual ASCT toxicities including diarrhea, mucositis, and neutropenic fever. All patients had normal neutrophil and platelet engraftments. 60% of patients had very good partial response or better after ASCT. All patients received post ASCT maintenance until progression/toxicity/patient decision. As of December 2020, 2 patients have died 51 and 85 months from ASCT due to other causes. The 3 remaining patients are alive 5-7 years after ASCT. MM patients with concurrent HIV infection that is controlled on ART would benefit from aggressive treatment with chemotherapy and ASCT, with continued ART as they tolerate ASCT as well as myeloma patients without HIV infection.

Beyond CPRA: Identifying Sensitized Kidney Candidates with Markedly Low Access to Deceased Donor Transplantation by Granular CPRA and Blood Type

Prioritization in the US Kidney Allocation System (KAS) has led to an improvement in the rates of transplantation in highly sensitized (HS) patients. However, there is a subset of HS patients who are at a disadvantage, despite prioritization under KAS. The purpose of this study was to describe the transplant rate (TR) by calculated panel reactive antibody (CPRA) of HS candidates before and five years post-KAS to characterize their access to deceased donor transplants and quantify the number of HS candidates who are at a marked disadvantage in accessing kidneys. Using de-identified OPTN data, the number of solitary deceased donor kidney transplants performed (by month) from June 2013 through December 2019 was analyzed for four CPRA groups (95–97%, 98%, 99%, and 100%), with the CPRA 100% group further stratified into two subgroups (99.5–99.9% and >99.9%). The impact of the recipient blood group was assessed as an additional factor in TR. Immediately after KAS, TR rose 7-fold from 0.26% to 1.7% for the CPRA 99–100% group as a whole, and 12-fold and 8-fold for the CPRA 99.5–99.9% and CPRA 99.9%+ groups, respectively. However, the post-KAS mean TR of 0.63% for CPRA 99.9%+ candidates remained markedly lower than the mean TR of the other sensitized groups: 1.5% for CPRA 95–97%, 1.4% for CPRA 98%, 2.0% for CPRA 99%, and 3.5% for CPRA 99.5–99.9%; a statistically significant 6-fold advantage of the CPRA 99.5–99.9% group over CPRA 99.9%+ candidates was observed, despite both groups receiving national priority under KAS. Patients with a CPRA of 99.9%+ and blood group B were 2.16, 1.98, and 1.75 times less likely to receive a transplant compared to the same CPRA group with blood groups A, AB, and O, respectively, despite changes to KAS allocating blood type A2 and A2B to recipients with blood group B. Although the TR increased sharply for the CPRA 99.9%+ group with KAS, it remained markedly lower than the average despite national priority.

Sarcopenia; An Endemic in the Times of Pandemic in Liver Transplantation

Liver transplantation (LT) has grown monumentally in the last 40 years. Sarcopenia has emerged as an independent factor associated with increased mortality in patients with end stage liver disease. In this review we aim to shed light upon recent developments in assessment, clinical implications, management of sarcopenia in patients requiring a liver transplant. We also bring attention to the impact of COVID-19 pandemic on sarcopenia which ranges from the disease pathology to the unprecedented preventive measures taken during this time. Assessment tools to risk stratify and assess the degree of COVID related deconditioning in patients with end stage liver disease is an exigency. Management of sarcopenia requires a multifarious approach to address nutritional factors, exercise and pharmacotherapy. We may have to shift gears to focus on more rigorous rehabilitation and nutritional techniques during the times of pandemic. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable and whether that improvement in muscle mass leads to an improvement in clinical outcomes. Data regarding long term and short-term effects of COVID 19 pandemic, to form assessment tools that aim to identify patients who can benefit from multimodal prehabilitation and rehabilitation, is required.

Predictors of Mid-Term Glomerular Filtration Rate after Deceased Donor Renal Transplantation: Kidney Donor Profile Index as a Predictor of Mid-Term GFR

Glomerular filtration rate (GFR) is an excellent indicator of renal function; however, it is rarely evaluated as an endpoint. We investigated donor and recipient factors for associations that might be predictive of mid-term GFR after renal transplantation. We performed a retrospective review of 828 deceased donor renal transplantations performed at Montefiore Medical Center between the years 2009-2015. Donor characteristics included KDPI, [low (<20%), medium (20-80%), high (>80%)], age, graft types [extended criteria (ECD), cardiac death (DCD), standard criteria (SCD)], CDC high risk, HCV status and cold ischemic time (CIT). Recipient factors included age at transplant, induction agent, BK status, CMV status, acute and chronic rejection, cPRA and DSA status. Primary outcome is 3-year GFR calculated via the MDRD equation. In univariate analysis, donor age, KDPI, ECD, and chronic rejection were significantly associated with changes in 3-year GFR (p<0.001). In the multivariable regression analysis, donor age, KDPI, and chronic rejection remained associated with changes in 3-year GFR (p<0.001). Acute rejection, DCD, HCV status, CIT, BK and CMV viremia, PRA, pretransplant or de novo DSA were not associated with changes in 3-year GFR (p>0.05). We conclude that donor age, KDPI, and chronic rejection are independently associated with 3-year GFR while acute rejection, DCD, HCV status, CIT, BK and CMV viremia, PRA, existing or de novo DSA were not. Based on these findings, current scoring systems may need refinement to address the prognosis of mid-term GFR.