Chronic Graft Research Articles

Efficacy of a Standardized Regimen of Therapeutic Plasma Exchange and IVIG for Treatment of Antibody-Mediated Rejection in Lung Transplant Recipients.

Antibody-mediated rejection (AMR) in lung transplantation has been associated with poor long-term clinical course and is a risk factor for chronic lung allograft dysfunction and graft loss. Appropriate management of AMR is necessary to improve graft survival in lung transplant recipients. There is currently no standardized approach to the treatment of lung AMR, and practices vary by institution. We sought to examine the efficacy of a standardized protocol of plasma exchange (PLEX) and IVIG in decreasing donor-specific antibodies (DSAs) and improving AMR in lung transplant recipients. A retrospective chart review was conducted on all lung transplant recipients who completed a course of PLEX per UT Southwestern AMR protocol between January 2012 and December 2019 for diagnosis of AMR. Data were collected on the patient clinical course, treatment regimen, pre-PLEX DSA, post-PLEX DSA, follow-up (> 1-month post-PLEX) DSA, and pre-and post-PLEX biopsy, when available. Of 527 patients who underwent lung transplantation during the study period, 56 (11%) received an acute course of PLEX every other day per protocol for AMR of lung transplant. Forty (71%) of 56 patients had one episode of AMR requiring PLEX; 16 patients (29%) had repeat episodes of AMR within 6 weeks to 47 months of the first episode. Most patients showed improvement in AMR on biopsy (69%) and a decline in DSA (68%). Our data suggest that treatment with combined PLEX and IVIG protocol appears effective for treating lung AMR.

Donor-specific Immune Senescence as a Candidate Biomarker of Operational Tolerance Following Liver Transplantation in Adults: Results of a Prospective, Multicenter Cohort Study

Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in non-autoimmune, non-viral adult liver transplant recipients. Enrolled subjects were ≥3 years post-transplant with minimal/absent inflammation or fibrosis on a screening liver biopsy. The primary endpoint was operational tolerance at 52 weeks following complete ISW. Of 61 subjects who initiated ISW, 34 failed during ISW and 10 restarted immunosuppression due to clinically manifest acute rejection. Of the 17 subjects remaining off immunosuppression at 1 year, 10 were ultimately deemed tolerant by biopsy. There were no cases of chronic rejection or graft loss. The majority of subjects (78.6%), including those who experienced rejection, ended the study on same or less calcineurin inhibitor than at baseline. 28.3% developed de novo DSA during ISW, which persisted in 11.3%. A minority (16.4%) of histologically and clinically stable long-term adult liver transplant recipients can successfully discontinue and remain off immunosuppression. Increased frequency of donor-specific T cell senescence, C4d deposition and higher density of immune synapses on the screening liver biopsy emerged as potential candidate biomarkers for operational tolerance. NCT02533180.

Microbiota signature of oral chronic graft-versus-host disease 6+ years after transplantation.

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Human leukocyte antigen mismatch and circulating donor-specific antibodies predict graft loss after kidney transplantation: A retrospective study from Campania region – Italy

Donor-specific antibodies (DSA) are an established biomarker predicting antibody-mediated rejection, as the leading cause of graft loss after kidney transplantation. Furthermore, human leukocyte antigen (HLA) matching offers a more precise assessment of donor-recipient HLA compatibility and may prevent more effectively sensitization against allograft tissue. Indeed, increased number of HLA mismatches (MM) is significantly associated with a higher risk of immunological rejection, de novo DSA (dnDSA) development, and graft failure. Over the last decade, a comprehensive approach to optimize kidney matching and monitor transplant recipients for acute and chronic graft dysfunction was the goal for the success of the kidney transplantation. In our long-term retrospective study, we have found that pre- and post-transplantation HLA antibodies were significantly associated with de novo dnDSA occurrence (pre-transplant HLA Class I antibodies p = 0.039p < 0.05; pre-transplant HLA Class II antibodies p = 0.011p < 0.05; post-transplant HLA Class I non-DSA antibodies p < 0.01; post-transplant HLA Class II non-DSA antibodies p < 0.01). In addition, HLA MM at locus A (hazard ratio (HR), 2.44; 95 % confidence interval (CI): 1.15–5.16; p = 0.01 hazard ratio (HR), 2.33; 95 % confidence interval (CI):1.132–4.805; p = 0.02) and DSA Class I (HR, 10.24; 95 % CI: 1.44–72.62; p = 0.02 HR, 5.539; 95 % CI: 1.264–24.272; p = 0.02) appeared to be significant predictors of poorer graft survival. Our investigation demonstrates the long medium-term experience of DSA development occurrence in patients with after kidney transplantation in Campania region – Italy.

Ibrutinib for therapy of steroid-refractory chronic graft vs. host disease: A multicenter real-world analysis

To examine activity of ibrutinib in steroid-refractory chronic GVHD (SR-cGVHD) after FDA approval, we conducted a multicenter retrospective study. Data were standardly collected (N=270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), GI (26%), lung (27%), liver (19%), genital (7%), other (4.4%). NIH severity was mild in 5.7%, moderate 42%, severe 53%. 39% had overlap subtype. KPS was ≥ 80% in 72%. Median prednisone (mg/kg) was 0.21 (0-2.27). Ibrutinib was started at median of 18.2 months after cGVHD onset and in earlier lines of therapy (2nd line: 26%, 3rd: 30%, 4th: 21%, 5th: 9.6%, 6th: 10%, 7th or higher: 1.2%)). Among evaluable subjects, the 6 month NIH overall response rate (CR/PR) was 45% (PR 42%, CR 3%). Median duration of response was 15 months (range 1-46). Liver involvement had association with 6 month ORR (multivariate (MVA) OR 5.49 (95% CI 2.3-14.2, p <0.001). Best overall response was 56%, with most (86%) achieving by 1-3 months. With median follow up for survivors of 30.5 months, FFS was 59% (53-65%) at 6 months and 41% (36-48%) at 12 months. On MVA, increased age (HR 1.01, 95% CI 1.0-1.02, p=0.033), higher baseline prednisone (HR 1.92, 1.09-3.38, p=0.032), and lung involvement (HR 1.58, 1.1-2.28, p=0.016) had worse FFS. Ibrutinib discontinuation was most commonly due to progressive cGVHD (44%) or toxicity (42%). These data support that ibrutinib has activity in SR-cGVHD, provide new insight into factors associated with response and FFS, and demonstrate the toxicity profile associated with discontinuation.

The Impact of FDA-Approved Novel Agents for Steroid-Refractory Chronic Graft vs. Host Disease on Treatment Patterns and Outcomes—A Single-Center Longitudinal Cohort Analysis

Objectives—chronic graft vs. host disease (cGVHD) is associated with substantial morbidity and mortality. We aimed to analyze advances in treatment strategy and outcomes during the last decade due to the incorporation of novel immunosuppressive therapy (IST) drugs in the armamentarium. Methods—we retrospectively analyzed all patients &gt; 18 years with cGVHD after their first hematopoietic cell transplantation (HCT) between 2012 and 2020 (n = 91), divided into three treatment periods: 2012–2014, 2015–2017, and 2018–2020 (groups 1, 2, and 3, respectively). Results—mean cumulative steroid dose and dose/total cGVHD-treatment days was lower in groups 2–3 compared to 1 (p = 0.008 and p = 0.042, respectively). The median IST-free survival was 79 (95%CI54–94) months, with more patients in group 3 (47% (95%CI 25–54%) discontinuing IST at 3 years, p = 0.1). Groups 2–3 compared to 1 had better glycemic control (p &lt; 0.01), higher bone density (p = 0.06), and fewer cardiovascular events. The number of admissions/patient dropped from 0.7/year in group 1 to 0.24/year and 0.36/year in groups 2–3, respectively (p = 0.36). Employment reintegration was higher in groups 2–3 compared with 1 (p = 0.05) and so was earlier return to work (p = 0.01). There were no differences in survival outcomes. Conclusions—the incorporation of novel agents appears to be associated with reduced overall steroid burden, improved cGVHD control, and fewer long-term side effects.

NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection.

Chronic graft rejection represents a significant threat to long-term graft survival. Early diagnosis, understanding of the immunological mechanisms and appropriate therapeutic management are essential to improve graft survival and quality of life for transplant patients. Knowing which immune cells are responsible for chronic vascular rejection would allow us to provide effective and appropriate treatment for these patients. It is now widely accepted that natural killer (NK) cells play an important role in chronic vascular rejection. They can either initiate chronic vascular rejection by recognizing missing self on the graft or be recruited by donor-specific antibodies to destroy the graft during antibody-mediated rejection. Whatever the mechanisms of activation of NK cells, they need to be primed to become fully activated and damaging to the graft. A better understanding of the signaling pathways involved in NK cell priming and activation would pave the way for the development of new therapeutic strategies to cure chronic vascular rejection. This review examines the critical role of NK cells in the complex context of chronic vascular rejection.

Commentator Discussion: Chronic total occlusions and coronary artery bypass grafting outcomes

Commentator Discussion: Chronic total occlusions and coronary artery bypass grafting outcomes

Belatacept-related cytomegalovirus infection: Advocacy for tailored immunosuppression based on individual assessment of immune fitness

Belatacept, a fusion protein combining CTLA-4 and the Fc region of human IgG1, is increasingly used as a calcineurin inhibitor–sparing regimen in patients with chronic graft dysfunction. Older kidney transplant recipients, particularly from expanded criteria donors, may be switched to belatacept due to poor renal recovery. However, late-onset cytomegalovirus (CMV) reactivation is increasingly reported with this treatment, especially in older patients with graft dysfunction. This suggests a progressive loss of CMV-specific T cell response, potentially driven by T cell exhaustion. Contributing factors include preexisting T cell dysfunction, increased viral antigen exposure, and interference in the PD-L1/PD-1 pathway by belatacept. mTOR inhibitors have shown efficacy in preventing CMV reactivation by reinvigorating CMV-specific T cells. These findings support combining belatacept with mTOR inhibitors in high-risk CMV-seropositive recipients and emphasize the need for personalized immune assessments to guide immunosuppressive strategies.

Biobehavioral mechanisms underlying symptoms in cancer patients with chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplant (HCT) and is associated with morbidity and high symptom burden. This study evaluated two biobehavioral mechanisms, inflammation and circadian rest-activity rhythms, that may underly commonly reported psychological and physical symptoms in cGVHD patients. Adults with cGVHD (N=57) wore a wrist actigraph for 7 days, provided a blood sample, and completed patient-reported outcome (PRO) measures. 24-hour rest-activity indices were derived from actigraphy. Cytokines and chemokines relevant to cGVHD were measured in peripheral blood plasma using multi-analyte immunoassays. Multiple regression evaluated the extent to which rest-activity indices and inflammatory biomarkers predicted PROs. Higher levels of circulating IL-8 and MIP-1α were associated with worse depression (β = 0.35, p = 0.01; β = 0.33, p = 0.02) and sexual function (β = -0.41, p = 0.01; β = -0.32, p = 0.03). MIP-1α was associated with more severe insomnia (β = 0.36, p = 0.01). Higher circulating MIF was associated with more severe anxiety (β = 0.28, p = 0.048) and fatigue (β = 0.35, p = 0.02). Il-6, TNFα, and MCP-1 showed few associations with PROs. There were few associations between actigraphy indices and PROs; however, participants with a later daily activity peak (acrophase) reported poorer sexual function (β = -0.31, p = 0.04). Models covarying for age, cGVHD severity, and time since HCT yielded a similar pattern of results. Results suggest that pro-inflammatory cytokines and chemokines associated with cGVHD may contribute to PROs, identifying a biobehavioral mechanism that may be a useful target for future interventions.

Sustained HIV remission after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells.

HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4+ T cells obtained after antiretroviral treatment interruption, while CD4+ T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5.

52401 Phototherapy for the Treatment of Acute and Chronic Cutaneous Graft versus Host Disease

52401 Phototherapy for the Treatment of Acute and Chronic Cutaneous Graft versus Host Disease

Does Chronic Obstructive Pulmonary Disease Impact Outcome after Coronary Artery Bypass Grafting? A Population-Based Retrospective Study in Germany.

Background: The interaction between chronic obstructive pulmonary disease (COPD) and coronary artery bypass grafting (CABG) is discussed controversial. Methods: In this population-based retrospective analysis including non-emergency CABG in Germany between 2015 and 2021, the aim was to compare in-hospital mortality, hospital length of stay (HLOS), and perioperative ventilation time (VT) in patients affected by COPD and not affected by COPD. In addition, we compared outcomes after off-pump coronary artery bypass (OPCAB) and on-pump coronary artery bypass (ONCAB) surgery and outcomes after CABG with a minimally invasive technique with and without cardiopulmonary bypass (CPB) in COPD patients. Results: Of the 274,792 analyzed cases undergoing non-emergency CABG, 7.7% suffered from COPD. COPD patients showed a higher in-hospital mortality (6.0% vs. 4.2%; p < 0.001), a longer HLOS (13 days (10-19) vs. 12 days (9-16); p < 0.001), and a longer VT (33 h (11-124) vs. 28 h (9-94); p < 0.001). In subgroup analyses, COPD patients undergoing OPCAB surgery showed a lower in-hospital mortality (3.5% vs. 6.4%; p < 0.001), a shorter HLOS (12 days (9-16) vs. 13 days (10-19); p < 0.001) and a shorter VT (20 h (10-69) vs. 36 h (11-135); p < 0.001) compared to ONCAB surgery. Regression analyses confirmed that using cardiopulmonary bypass in COPD patients is associated with a higher risk of in-hospital mortality (OR, 1.86; 95% CI: 1.51-2.29, p < 0.001), a longer HLOS (1.44 days; 95% CI: 0.91-1.97, p < 0.001), and a longer VT (33.67 h; 95% CI: 18.67-48.66, p < 0.001). In further subgroup analyses, COPD patients undergoing CABG with a minimally invasive technique without CPB showed a lower in-hospital mortality (3.5% vs. 16.5%; p < 0.001) and a shorter VT (20 h (10-69) vs. 65 h (29-210); p < 0.001) compared to CABG with a minimally invasive technique and CPB. Regression analyses confirmed that using CPB in COPD patients undergoing CABG with a minimally invasive technique is associated with a higher risk of in-hospital mortality (OR, 4.80; 95% CI: 2.42-9.51, p < 0.001). Conclusions: COPD negatively impacts outcomes after non-emergency CABG. According to our results, OPCAB surgery and CABG with a minimally invasive technique without CPB seem to be beneficial for COPD patients. Further studies should be performed to confirm this.

Characterization of ibrutinib's effects on the morphology, proliferation, phenotype, viability, and anti-inflammatory potential of adipose-derived mesenchymal stromal cells

Ibrutinib (IB) is a tyrosine kinase inhibitor (TKI) that has immunomodulatory action and can be used as second-line therapy for steroid-refractory or steroid-resistant chronic Graft versus Host Disease (cGVHD). Mesenchymal stromal cells (MSCs) are distributed throughout the body and their infusion has also been explored as a second-line therapeutic alternative for the treatment of cGVHD. Considering the currently unknown effects of IB on endogenous MSCs, as well as the possible combined use of IB and MSCs for cGVHD, we investigated whether adipose tissue-derived MSCs present IB-targets, as well as the consequences of treating MSCs with this drug, regarding cell viability, proliferation, phenotype, and anti-inflammatory potential. Interestingly, we show for the first time that MSCs express several IB target genes. Also of note, the treatment of such cells with this TKI elevated the levels of CD90 and CD105 surface proteins, as well as VCAM-1. Furthermore, IB-treated MSCs presented increased mRNA expression of the anti-inflammatory genes PD-L1, TSG-6, and IL-10. However, continued exposure to IB, even at low doses, compromised the viability of MSCs. These data indicate that the use of IB can stimulate an anti-inflammatory profile in MSCs, but also that a continued exposure to IB can compromise MSC viability over time.

Chronic total occlusions and coronary artery bypass grafting outcomes

ObjectiveTo investigate the association between the presence and grafting of chronic total occlusions (CTOs) and coronary artery bypass grafting (CABG) outcomes. MethodsThis was a post hoc analysis of the Randomized Endograft vs Open Prospective (REGROUP) trial, which randomized veterans undergoing isolated on-pump CABG to endoscopic versus open vein harvest (2014-2017). Patients were stratified on the basis of the presence of at least 1 CTO vessel (a 100% occluded coronary lesion for greater than or equal to 3 months) and according to whether all CTO vessels were bypassed. Rates of major cardiac adverse events (MACE) were compared. ResultsAt least 1 CTO was present in 453 of 1149 patients (39.4%). Over a median follow-up of 4.7 years (interquartile range, 3.84-5.45), MACE rates were 23.4% versus 22.2% for the CTO versus no CTO group, respectively (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.70-1.20). MACE rates for patients with complete CTO grafting versus not were 23.1% versus 25.0%, respectively (aHR, 0.95; 95% CI, 0.57-1.57). In patients with right coronary dominance undergoing left anterior descending artery grafting, bypassing a right coronary artery CTO was associated with significantly lower rates of all-cause mortality (aHR, 0.38; 95% CI, 0.17-0.83). ConclusionsIn this REGROUP trial subanalysis, neither CTO presence or complete grafting of CTO vessels was associated with significantly different rates of MACE. However, the finding of possible survival benefit among a subgroup of patients undergoing grafting of a dominant RCA CTO vessel alongside left anterior descending artery grafting warrants additional study.

Complications associated with kidney transplantation, causes of graft failure and mortality following kidney transplantation in patients with systemic lupus erythematosus: a meta-analysis

IntroductionDespite improvement in the management of systemic lupus erythematosus (SLE) during the past two decades, 10–22% of patients with lupus nephritis (LN) will progress to end-stage renal disease (ESRD). Kidney transplantation is among the possible treatment for patients with SLE progressing to ESRD. However, the issue with kidney transplantation in patients with SLE is controversial. In this analysis, we aimed to compare the complications associated with kidney transplantation, causes of graft failure and causes of mortality following kidney transplantation in patients with SLE with ESRD.MethodsThe sources of data included http://www.ClinicalTrials.gov, EMBASE, MEDLINE, Google Scholar, Web of Science and the Cochrane database. Revman software version 5.4 was used for the data analysis whereby risk ratio (RR) with 95% confidence intervals (CI) were used to represent data following analysis. In addition, the Q statistic test and the I2 statistic test were used to assess heterogeneity. A random effect statistical model was used and a subgroup outcome with a P-value less than 0.05 was considered statistically significant.ResultsA total number of 149,330 participants enrolled between the years 1968 and 2018 were included in this analysis with 7534 participants with SLE.Results of this analysis showed that mortality (RR 1.07, 95% CI 0.89–1.29; P = 0.45), graft failure (RR 1.22, 95% CI 0.99–1.55; P = 0.07) and delayed graft function (RR 1.01, 95% CI 0.44–2.34; P = 0.98) were not significantly higher in renal transplant patients with SLE versus a control group. When the causes of graft failure were analysed in renal transplant patients with SLE versus without SLE, acute graft rejection (RR 1.20, 95% CI 0.98–1.47; P = 0.07), chronic graft rejection (RR 0.76, 95% CI 0.57–1.03; P = 0.08), graft thrombosis (RR 1.47, 95% CI 0.83–2.63; P = 0.19), recurrence of disease (RR 3.08, 95% CI 1.00–9.47; P = 0.05) and chronic allograft nephropathy (RR 1.08, 95% CI 0.60–1.95; P = 0.80) were also not significantly higher in patients with SLE. On the basis of the analysis, mortality from any cardiac cause (RR 0.82, 95% CI 0.67–1.01; P = 0.06), sepsis (RR 1.19, 95% CI 0.93–1.53; P = 0.17), malignancy (RR 0.79, 95% CI 0.51–1.24; P = 0.31) and cerebrovascular attack (RR 0.76, 95% CI 0.44–1.30; P = 0.31) were not significantly different in kidney transplantation patients with versus without SLE.ConclusionsComplications associated with kidney transplantation including mortality, graft failure and delayed graft function were not significantly higher in patients with SLE when compared with a control group. The causes of graft failure and mortality after kidney transplantation were also comparable in both groups. Therefore, kidney transplantation represents a promising treatment in patients with SLE with ESRD.

MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.

Tissue fibrosis remains unamenable to meaningful therapeutic interventions and is the primary cause of chronic graft failure after organ transplantation. Eukaryotic translation initiation factor (eIF4E), a key translational regulator, serves as convergent target of multiple upstream profibrotic signaling pathways that contribute to mesenchymal cell (MC) activation. Here, we investigate the role of MAP kinase-interacting serine/threonine kinase-induced (MNK-induced) direct phosphorylation of eIF4E at serine 209 (Ser209) in maintaining fibrotic transformation of MCs and determine the contribution of the MNK/eIF4E pathway to the pathogenesis of chronic lung allograft dysfunction (CLAD). MCs from patients with CLAD demonstrated constitutively higher eIF4E phosphorylation at Ser209, and eIF4E phospho-Ser209 was found to be critical in regulating key fibrogenic protein autotaxin, leading to sustained β-catenin activation and profibrotic functions of CLAD MCs. MNK1 signaling was upregulated in CLAD MCs, and genetic or pharmacologic targeting of MNK1 activity inhibited eIF4E phospho-Ser209 and profibrotic functions of CLAD MCs in vitro. Treatment with an MNK1/2 inhibitor (eFT-508) abrogated allograft fibrosis in an orthotopic murine lung-transplant model. Together these studies identify what we believe is a previously unrecognized MNK/eIF4E/ATX/β-catenin signaling pathway of fibrotic transformation of MCs and present the first evidence, to our knowledge, for the utility of MNK inhibitors in fibrosis.

Norovirus Management and Outcomes in a Multicenter Pediatric Kidney Transplant Population.

Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2-11.2 years), and median time post-transplant was 1.9 years (IQR 0.8-3.8 years). Median diarrheal duration was 16 days (IQR 6.0-41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty-one (53%) patients developed acute kidney injury. Thirty-five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: -17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment.

Buschke – Lowenstein Tumor. Case Report in a Patient with a History of Kidney Transplantation with Chronic Graft Rejection

Buschke-Lo wenstein tumor is a rare disease characterized by aggressive local infiltration in the perineal region, associated with human papillomavirus infection. It primarily affects immunocompromised patients, with surgical resection being the mainstay of treatment. We report the case of an adolescent with a history of chronic immunosuppression due to vasculitis and subsequent renal complications, including terminal chronic kidney disease and renal transplant failure. At 16 years old, she was diagnosed with Buschke-Lo wenstein tumor and underwent surgical treatment with complete lesion excision.

Impact of Race and Ethnicity on Outcomes After Umbilical Cord Blood Transplantation

BackgroundUmbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. ObjectiveTo compare outcomes by social determinants of health. Study DesignWe designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N = 1752) or reduced intensity conditioning (N = 759) for acute myeloid leukemia, acute lymphoid leukemia, or myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). ResultsFor 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6 to 45.3) for Whites, 36.1% (99% CI, 28.2 to 44.5) for Latinx, 45.8% (99% CI, 36.7 to 55.1) for Blacks, and 44.5% (99% CI, 33.6 to 55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p = .0005, HR 1.45, 99% CI 1.18 to 1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7 to 72.2) for Whites, 57.1% (99%CI, 49 to 64.9) for Latinx, 46.8% (99%CI, 35.3 to 58.4) for Blacks, and 53.8% (99%CI, 32.7 to 74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = .051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p = .0016, HR 2.25, 99% CI 1.36 to 3.74) and Latinx (p = .0016, HR 2.17, 99% CI 1.43 to 3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults.Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p = .03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p = .02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p = .02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. ConclusionsOS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.