Risk Factor For Graft Failure Research Articles

Incidence and risk factors of graft failure in allogeneic hematopoietic stem cell transplantation for mucopolysaccharidosis in a nationwide pediatric cohort. A study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

AbstractContextMucopolysaccharidosis (MPS) requires urgent treatment to prevent neurological damage. While gene therapy holds promise for effectively treating these diseases with minimal toxicity, access remains limited for most patients. Consequently, advancing allogeneic hematopoietic stem cell transplantation (HSCT) for young children is crucial. Since the 2010s, cord blood (CB) transplants with reduced‐toxicity conditioning (RTC) have become the standard of care.Patients and methodsRecent reports in France indicate a significant incidence of graft failures (GF), prompting a large‐scale retrospective study from the French‐speaking bone marrow transplantation society's registry, to understand GF risks, guide clinicians in selecting transplant platforms, and describe outcomes of second HSCT in young patients.ResultsThis report analyses 93 children who underwent HSCT for MPS between 2000 and 2020. The GF rate was notably high (22.6% at day 100), primarily associated with the donor's HLA compatibility and the recipient's age. Well‐matched CB and RTC were not found to be risk factors for GF. This study also details the procedures for second and third transplants in patients who rejected their first HSCT.ConclusionIn the era of RTC, CB remains a viable and expedient option for MPS transplantation.

Clinical characteristics, risk factor analysis and outcomes in 61 eyes with graft rejection after descemet stripping endothelial keratoplasty, with a review of literature.

To report the demographic profile, clinical characteristics, risk factors and outcomes of graft rejection after DSEK. A total of 3073 eyes had DSEK between 2012 and 2019, of which 1710 eyes that had follow up of more than one year. Sixty-one eyes who had graft rejection during this period were studied. Overall, incidence of graft rejection during the study period was 3.6% (61/1710 eyes) in those with follow up more than one year. The median age of patients was 58 (IQR 37.5-68) years. The indications were prior failed graft (34 eyes: 28 penetrating keratoplasty; 6 DSEK), post cataract surgery edema (12 eyes), Fuchs corneal endothelial dystrophy (6 eyes), corneal edema post inflammation (5 eyes) and iridocorneal endothelial syndrome (4 eyes). Of the 34 eyes with failed grafts, nine were post-rejection graft failures (two after endothelial keratoplasty and seven after penetrating keratoplasty), remaining 25 eyes were non-rejection graft failures. Ocular co-morbidities were noted in 41 eyes, of which secondary glaucoma was the most common (14 eyes). Clinical signs of graft rejection were diffuse edema, keratic precipitates and endothelial rejection line. Rejection episode occurred between 6-12months after surgery in 20 (33%) eyes, 12-24months in 15 (25%) eyes, 2-3years in 12 (20%) eyes, and beyond 3years in 14(23%) eyes. Graft clarity was restored in 55 (90%) eyes, which was complete in 41 (67%) eyes, partial in 14 (23%) eyes, and clarity was not restored in 6 (10%) eyes. The statistically significant risk factors for rejection were non-use of steroids (p value < 0.001), DSEK for failed graft (p value < 0.02) and DSEK for corneal edema post-inflammation (p value < 0.0014). DSEK for failed graft was a significant risk factor for graft failure after the rejection episode (p value < 0.05). Graft rejection may occur as late as 5years post-DSEK, emphasizing the need for long-term steroids instillation. Non-use of topical steroids, DSEK for failed graft and corneal edema post inflammation are risk factors for graft rejection. DSEK for failed graft was also seen as a risk factor for failure after the rejection episode The graft survival rate after the rejection episode was 90% at 6months, 50% at 2years and 10% at 5years.

Corneal Endothelial Keratoprosthesis EndoArt in Patients with Glaucoma at High Risk of Graft Failure After Keratoplasty.

The novel endothelial keratoprosthesis EndoArt improves corneal edema by reducing the inflow of aqueous humor into the cornea. We assessed the early outcome after EndoArt implantation in patients at a high risk of graft failure after keratoplasty. This retrospective study included 14 patients with high-risk eyes owing to at least one of the following risk factors for graft failure after keratoplasty: multiple previous surgeries (glaucoma surgery, keratoplasty) and recurrent intraocular inflammation because of uveitis, aniridia, or anterior synechia. After descemetorhexis, the EndoArt keratoprosthesis was placed on the posterior stroma, secured with a gas bubble and 1 to 3 transcorneal holding sutures. Best spectacle-corrected visual acuity and central corneal thickness were calculated preoperatively and postoperatively. In addition, detachment of the keratoprosthesis and the need for additional gas injections (rebubbling) were analyzed. Octafluoropropane (C3F8) 12% in 11 patients and sulfur hexafluoride 20% in 3 patients were used to attach EndoArt. Detachments requiring at least 1 rebubbling occurred in 8 eyes. Preoperative best spectacle-corrected visual acuity was 1.6 (±0.6) logarithm of the minimal angle of resolution and improved to 1.3 (±0.6) after 12 weeks. Preoperative central corneal thickness (771.8 μm ± 157) significantly decreased postoperatively in all patients (622.1 μm ± 184.7 [P = 0.025] and 562.8 μm ± 183.6 [P = 0.012] after 6 and 12 weeks, respectively). EndoArt improved visual acuity and significantly reduced corneal thickness within 3 months postoperatively, subjectively, but not statistically significantly. The rebubbling rates in this cohort with an altered anterior segment anatomy were relatively high. Patients at a high risk of graft failure may benefit from this novel endothelial keratoprosthesis.

Graft Failure and Contralateral ACL Injuries After Primary ACL Reconstruction: An Analysis of Risk Factors Using Interpretable Machine Learning.

Anterior cruciate ligament (ACL) reconstruction (ACLR) can be successful in restoring knee stability. However, secondary ACL injury, either through graft failure or contralateral injury, is a known complication and can significantly impact the ability of a patient to return successfully to previous activities. To develop and internally validate an interpretable machine learning model to quantify the risk of graft failure and contralateral ACL injury in a longitudinal cohort treated with ACLR. Case-control study; Level of evidence, 3. An established geographic database of >600,000 patients was used to identify patients with a diagnosis of ACL rupture between 1990 and 2016 with a minimum 2-year follow-up. Medical records were reviewed for relevant patient information and 4 candidate machine learning algorithms were evaluated for prediction of graft failure and contralateral ACL injury in patients after ACLR as identified either on magnetic resonance imaging or via arthroscopy. Performance of the algorithms was assessed through discrimination, calibration, and decision curve analysis. Model interpretability was enhanced utilizing global variable importance plots and partial dependence curves. A total of 1497 patients met inclusion criteria. Among them, 140 (9.4%) had graft failure and 128 (8.6%) had a contralateral ACL injury after index surgery at a median follow-up of 140.7 months (interquartile range, 77.2-219.2 months). The best performing models achieved an area under the receiver operating characteristics curve of 0.70 for prediction of graft failure and 0.67 for prediction of contralateral ACL injury, outperforming a logistic regression fitted on the identical feature set. Notable predictors for increased risk of graft failure included younger age at injury, body mass index (BMI) <30, return to sports <13 months, initial time to surgery >75 days, utilization of allograft, femoral/tibial fixation with suspension/expansion devices, concomitant collateral ligament injury, and active or former smoking history. Predictors of contralateral ACL injury included greater preoperative pain, younger age at initial injury, BMI <30, active smoking history, initial time to surgery >75 days, history of contralateral knee arthroscopies, and involvement in contact sports. Less than 18% of all patients who undergo ACLR should be expected to sustain either a graft failure or contralateral ACL injury. Machine learning models outperformed logistic regression and identified greater preoperative pain, younger age, BMI <30, earlier return to higher activity, and time to surgical intervention >75 days as common risk factors for both graft failure as well as contralateral ACL injury after ACLR. Surgeon-modifiable risk factors for graft failure included allograft and femoral/tibial fixation with a suspension/expansion combination.

Age under 20 years, pre-operative participation in pivoting sports, and steep posterior tibial slope of more than 12° are risk factors for graft failure after double-bundle anterior cruciate ligament reconstruction.

Younger age and steep posterior tibial slope (PTS) have been reported as risk factors for graft failure after anterior cruciate ligament reconstruction (ACLR). Few studies have evaluated these risk factors simultaneously in a large cohort of patients undergoing double-bundle ACLR (DB-ACLR). Therefore, this retrospective study aimed to simultaneously investigate known risk factors such as PTS and age in DB-ACLR, determine their thresholds and calculate odds ratios (ORs). We investigated 482 knees that underwent DB-ACLR with a follow-up period of at least 2 years. Receiver operating characteristic analysis determined cut-off values for age and PTS for graft failure. Subsequently, logistic regression analysis was conducted to evaluate the effects of age, sex, height, weight, laterality, surgical waiting period, pre-operative sport type and level, meniscal injury, hyperextension, general joint laxity and PTS on graft failure. Graft failure was observed in 33 out of 482 knees (6.8%). Notably, the graft failure group was significantly younger (18.0 ± 5.0 years [standard deviation] vs. 30.4 ± 13.1 years, p < 0.01) and had a steeper PTS (11.9 ± 2.3° [standard deviation] vs. 9.6 ± 2.9°, p < 0.01) than the group with no graft failure. The cut-off values were 20.0 years for age (specificity, 64.6%; sensitivity, 87.9% and area under the curve, 0.808) and 12.0° for PTS (specificity, 70.9%; sensitivity, 69.7% and area under the curve, 0.734). Logistic regression analysis identified an age of <20 years (OR = 10.1; p < 0.01), PTS of ≥12° (OR = 5.6; p < 0.01) and pre-operative participation in pivoting sports (OR = 6.0; p < 0.01) as significant risk factors for graft failure. We identified an age of <20 years, PTS of ≥12° and pre-operative participation in pivoting sports as significant risk factors for graft failure after DB-ACLR. Level III.

Outcomes of donation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) lung transplantation

BackgroundDonation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). ResultsThe study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001).After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality.On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) ConclusionStudy findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Risk Factors for Graft Failure After Penetrating Keratoplasty in Eastern China from 2018 to 2021.

BACKGROUND Penetrating keratoplasty (PK) remains the most common corneal transplant method in China. In this paper we aim to analyze the outcomes and the potential factors associated with graft failures of PKs in one of the largest keratoplasty centers in Eastern China during the past 4 years. MATERIAL AND METHODS A retrospective review was performed on 502 eyes from 481 recipients undergoing PKs from January 2018 to December 2021 at the Eye and ENT Hospital of Fudan University. Graft failures presenting between the first postoperative day and 8 weeks were defined as early graft failure and failures presenting between 8 weeks and the end of the 1-year follow-up as late failure. Cox proportional hazards regression models and logistic regression models were used to assess the association between factors and failures. RESULTS Of the 93 failed cases, 36 were classified as early failure and 57 as late failure. Risk factors, expressed as hazard ratio (HR) and confidence interval (CI), for the failures include the following: burns (HR: 12.56, 95% CI [2.4, 65.71]), nonsuppurative inflammation (HR: 11.06, 95% CI [2.49, 49.03]), suppurative inflammation (HR: 12.49, 95% CI [2.76, 56.37]), immune disease (HR: 1.70, 95% CI [0.64, 4.48]), low donor endothelial cell density (ECD) (HR: 0.92/100 cells, 95% CI [0.87, 0.98]), and surgical complications (HR: 1.83, 95% CI [1.06, 3.17]). Two social factors were strongly negatively associated with late failures: completion of compulsory education (HR: 0.45, 95% CI [0.21-0.94]) and marriage (HR: 0.27, 95% CI [0.09-0.81]). CONCLUSIONS Indications, surgical complications, immune disease of the recipient, and lower donor ECD were risk factors for failure. Social factors also affect the ocular health after PK in the long term.

Repeat corneal transplantation in Southern China: Indications, surgical technique, outcomes, and risk factors for repeat keratoplasty failure.

To report the indications, surgical techniques, and outcomes of repeat keratoplasty and evaluate the risk factors for graft failure in the Chinese population. The medical records of 216 patients (243 cases) who underwent at least two keratoplasties at a leading eye hospital in southern China between 2011 and 2020 were retrospectively reviewed. Indications and surgical procedures for repeat corneal transplantation were analyzed. Kaplan-Meier survival analysis was used to determine the graft survival rate after repeat keratoplasty. A multivariable survival model was used to assess the risk factors. Repeated keratoplasties increased continuously from 2011 to 2020 (P = 0.002). The most common primary indication was infectious keratitis (38.7%), and the most common reason for repeat keratoplasty was graft rejection (30.04%). Regraft techniques included penetrating keratoplasty (PK) in 165 cases (67.9%), deep lamellar keratoplasty (DALK) in 52 cases (21.40%), and endothelial keratoplasty (EK) in 26 cases (10.7%). Median survival was 5.3, 6.8, and 6.4 years for PK, DALK, and EK, respectively. The 5-year survival rate was 53.5%, 66.6%, and 69.8% for PK, DALK, and EK, respectively. The median LogMAR visual acuity was 1.4 for PK, 0.75 for DALK, and 1.2 for EK at the end of the follow-up. Multivariate analysis revealed that graft rejection is a risk factor for repeat keratoplasty failure (P = 0.002). DALK and EK may provide better outcomes than PK in treating graft failure. Preventing and treating postoperative graft rejection may be key to improving regraft survival. These findings will aid in the management of failed corneal grafts.

Is the Preoperative Wound Culture Necessary Before Skin Grafting Minor Burns? A Pilot Study in a Low Resource Setting Burn Service.

The most common cited cause of split-thickness skin graft failure is infection and due to the association between bacterial findings in wound beds an attempt to decrease the bacterial burden before skin-grafting evolved. Thus, preoperative microbiology swabs of the wound bed became routine at some institutions prior to grafting. This is not standard practice in the Pietermaritzburg Burn Service. Emphasis is instead placed on a strict protocol of intraoperative wound bed preparation to promote adequate graft take. This pilot study aims to evaluate whether preoperative wound swabs are appropriate. We performed a prospective observational study to determine if positive wound cultures were associated with graft failure. All patients with a burn surface area of less than 10%, where delayed grafting (later than 28 days from the time of burn injury) was performed, from March to December 2021 were analyzed. Patient demographics, days from burn to graft, %TBSA burn, %TBSA grafted, whether sharp debridement prior to grafting in the same procedure was performed or not, use of topical gentamicin intraoperatively, graft outcome (% graft loss), need for regraft, and organism grown were recorded into an excel spreadsheet for analysis. The sample included 52 patients. Of these, 17 (31.5%) were female. The median %TBSA grafted was 8% (IQR 4%-13%) and similar in both groups. The median days from burn to grafting were 35 days. Thirty-nine patients (75%) had graft Take and 13 (25%) had graft Failure. In the failed group, the median % graft failure was 50% (30%-70%). Of the group with successful graft take, 90% were noted to have had a positive wound culture prior to grafting. A positive wound culture was not found to be a risk factor for graft failure (P = .993). Despite the positive wound cultures graft take was more than 90% in 75% of grafts performed and only 2/52 patients required supplementary grafting. We believe that this demonstrates that our local protocol is reasonable in this setting and that waiting for negative wound swabs prior to grafting should not be a reason to delay grafting.

Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.

Use of the modified meek technique for the coverage of extensive burn wounds

IntroductionAutologous split thickness skin grafting using meshing technique remains the preferred option for the management of deep dermal and full thickness burns. The limited donor site availability seen in patients with extensive burns, however, restricts use of the mesh grafting technique for skin expansion. Meek micrografting was developed to allow for greater expansion, and, therefore, more reliable treatment of extensive burns. This study aimed to present our outcomes using the Meek micrografting technique and identify risk factors for graft failure. MethodsA retrospective review of patients admitted to our large academic hospital who were treated with the Meek micrografting technique from 2013 to 2022 was conducted. Patient demographics, surgical characteristics and outcomes were reported. Regression analyses were performed to identify factors that influence graft take and reoperation rate. ResultsA total of 73 patients with a mean age of 45.7 ± 19.9 years and mean burn size of 60.0 ± 17.8%TBSA, with 45.3 ± 14.9% TBSA being third degree burns, received Meek transplantation. The mean graft take after removal of the pre-folded polyamide gauze at the tenth post-operative day was 75.8 ± 14.7%. Pre-treatment with use of an allograft, longer waiting time between admission and Meek grafting and transplantation over a dermal matrix were identified as positive predictors for graft take, while age was established as a negative predictor. ConclusionBy examining the outcomes of the Meek micrografting technique in extensive burn wounds we identified that preconditioning of the wound bed, through allograft or negative pressure wound therapy application, positively correlates with improved outcomes, including higher graft take. At the same time, older age was seen to negatively correlate with graft take. Overall, Meek transplantation displays a favorable safety profile with promising outcomes. Future prospective studies and clinical trials can optimize the procedure and help establish it as the golden standard for extensive and complex burns.

Time-Varying Determinants of Graft Failure in Pediatric Kidney Transplantation in Europe.

Little is known about the time-varying determinants of kidney graft failure in children. We performed a retrospective study of primary pediatric kidney transplant recipients (younger than 18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor, and transplant risk factors. Primary outcome was death-censored graft failure. We report on 4528 kidney transplantations, of which 68% with deceased and 32% with living donor. One thousand six hundred and thirty-eight recipients experienced graft failure, and 168 died with a functioning graft. Between 2011 and 2020, the 5-year graft failure risk was 10% for deceased donor and 4% for living donor kidney transplant recipients. Risk of graft failure decreased five-fold from 1990 to 2020. The association between living donor transplantation and the lower risk of graft failure was strongest in the first month post-transplant (adjusted hazard ratio, 0.58; 95% confidence interval, 0.46 to 0.73) and remained statistically significant until 12 years post-transplant. Risk factors for graft failure in the first 2 years were deceased donor younger than 12 years or older than 46 years, potentially recurrent kidney disease, and panel-reactive antibody >0%. Other determinants of graft failure included dialysis before transplantation (until 5 years post-transplant), human leukocyte antigen mismatch 2-4 (0-15 years post-transplant), human leukocyte antigen mismatch 5-6 (2-12 years post-transplant), and hemodialysis (8-14 years post-transplant). Recipients older than 11 years at transplantation had a higher risk of graft failure 1-8 years post-transplant compared with other age groups, whereas young recipients had a lower risk throughout follow-up. Analysis of the combined effect of post-transplant time and recipient age showed a higher rate of graft failure during the first 5 years post-transplant in adolescents compared with young transplant recipients. In contrast to deceased donor younger than 12 years, deceased donor older than 46 years was consistently associated with a higher graft failure risk. We report a long-term inverse association between living donor kidney transplantation and the risk of graft failure. The determinants of graft failure varied with time. There was a significant cumulative effect of adolescence and time post-transplant. The ideal donor age window was dependent on time post-transplant.

Umbilical Cord Blood Stem Cells As Third-Party Adjuvant Infusion in Human Leukocyte Antigen Antibody-Positive Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: The presence of human leukocyte antigen (HLA) antibodies, even if not donor-specific antibodies (DSA), is an important risk factor for graft failure (GF) or poor graft function (PGF) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is no ideal strategy for eradicating or descending HLA antibodies in this population. In the present study, we investigated the efficacy and safety of unrelated umbilical cord blood stem cells (CBCs) as a third-party adjuvant infusion in patients with HLA antibodies undergoing allo-HSCT. Methods:Patients undergoing allo-HSCT from July 2017 to June 2021 were enrolled in this study and HLA antibodies were routinely tested before transplantation. Patients were divided into three groups: Group A (patients with positive/weak positive HLA antibodies and with CBCs infusion), Group B (patients with HLA antibodies positive/weak positive without CBCs infusion), and Group C (patients without HLA antibody nor CBCs infusion). Single unrelated CBCs (HLA4/6 or more compatible ) were infused four hours before donor stem cells. The clinical characteristics of the patients and the paired donors were collected. The occurrence of granulocyte and platelet engraftment time, graft-versus-host disease (GVHD), cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, one-year and two-year relapse-free survival (RFS), transplantation-related mortality (TRM), and overall survival (OS) for all three groups of patients were also analyzed in this study. Results:A total of 90 patients were included in this study (17 in group A, 36 in group B, and 37 in group C). The baseline clinical characteristics of the patients were presented in Table 1. No obvious adverse effects were observed in the process of CBCs infusion. All the patients achieved 100% donor chimerism without CBCs engraftment. There were no significant differences in granulocyte and platelet engraftment time between the three groups. Two patients in Group A and C, and 3 patients in Group B developed PGF, respectively. There were no significant differences in the incidence and grades of acute or chronic GVHD among the three groups ( Figure A, B). In the first 3 months after allo-HSCT, the incidence of EBV reactivation was higher in patients in Group B than that in Group A and C, respectively ( Figure C). There were no significant differences in the CMV reactivation between the three groups in the first 3 months after transplantation ( Figure D). Patients in Group A and B both had lower 1-year RFS and higher 1-year TRM, compared with Group C, respectively ( Figure E, F). However, there were no significant statistical differences in 2-year RFS and TRM between the three groups. Although patients in Group A had longer 2-year OS than that in Group B, there were no significant differences between the two groups: Group A vs Group B (76.5% vs 55.6%, P = 0.194), Group B vs Group C (55.6% vs 85.5%, P &amp;lt; 0.05)( Figure G). A multifactorial Cox regression risk model was established to explore the risk factors affecting OS and suggested that patients' pre-transplantation status (with active malignant disease or minimal residual disease positive) and HLA antibodies pre-transplant were the most independent risk factors for OS (HR = 4.380, 95% CI = 1.544-12.427, P&amp;lt;0.05; HR = 0.196, 95% CI = 0.065-0.587, P&amp;lt;0.05). Conclusions: Patients with positive/weak positive HLA antibodies receiving CBCs as a third-party adjunctive infusion were safe, and there was a benefit in the incidence of EBV reactivation compared to such a population without CBCs infusion. The patients with negative HLA antibodies had higher 1-year RFS and lower 1-year TRM than those with positive/weakly positive HLA antibodies regardless CBCs infusion. Due to the small number of included cases, we will expand the sample number to further validate our results in the future.

Emapalumab for Treatment of Impending Graft Failure

Introduction: Immune-mediated graft failure (also termed graft rejection) is a feared complication of hematopoietic stem cell transplant (HSCT) and there is no effective intervention. Multiple pre-transplant risk factors for graft failure are known and recent studies from our groups identified interferon gamma (IFNγ) as a mechanistically important and pharmacologically targetable cytokine involved in graft failure pathophysiology. CXCL9, a downstream marker of IFNγ production, was also identified as a biomarker. We describe an international multicenter retrospective pooled analysis of emapalumab (EMA), an IFNγ neutralizing agent, for the prevention/treatment of immune-mediated graft failure after HSCT. Methods: The safety and preliminary efficacy of EMA were studied in predominantly pediatric patients who received EMA using two different strategies: 1) graft failure treatment and 2) graft failure prophylaxis. Patients at US centers were treated with EMA if they developed clinical and laboratory signs of graft failure after HSCT. All treatment patients met 2 or more of the following criteria: 1) HLA mismatched donor and/or prior graft failure, 2) unexplained fever &amp;gt;39°C (or &amp;gt;38°C if prior history of graft failure) after HSCT, 3) absolute neutrophil count decline after initial engraftment, 4) delayed neutrophil engraftment after HSCT, 5) real-time CXCL9 &amp;gt; 2.5x upper limit of normal (ULN). Temperature and CXCL9 cutoffs were based on a prior graft failure biomarker publication (Sabulski et al, Blood Advances 2021). Patients treated at European centers received prophylactic EMA to prevent graft failure if they were deemed at high-risk prior to transplant. High-risk patients had a prior history of graft failure after HSCT or had two or more of the following established risk factors: a) affected by a disease with high risk of graft failure, including acquired severe aplastic anemia, thalassemia, primary HLH; b) ex-vivo T cell-depleted stem cell product; c) transplant from unrelated cord blood unit or mismatched related/unrelated donor. Results: Thirty-six HSCTs used EMA for graft failure treatment or prophylaxis and were included in this study.EMA was used for graft failure treatment in 25 HSCTs wherein patients developed clinical and laboratory signs of graft failure (Table 1). Most HSCTs in the treatment cohort were performed for bone marrow failure syndromes (n=16). All patients tolerated EMA without complications and no side effects or infections were attributed to EMA. Fifty six percent (14/25) of patients treated with EMA for impending graft failure engrafted and had resolution of graft failure concerns, while the remaining 44% suffered graft failure. Responders had a median ANC of 0.29 x10 3 cells/μL (range 0.05-0.79) prior to EMA, which increased to a median of 0.6 x10 3cells/μL (range, 0-5.1) and 2.97 x10 3 cells/μL (range, 0.85-8.7) on days 3 and 7 after EMA dosing. Eighty percent (20/25) of CXCL9 levels were elevated in the treatment cohort prior to EMA dosing. The median CXCL9 level prior to EMA dosing was elevated 2.4 x ULN (range, 0.3-157.8). The median pre-EMA CXCL9 level in patients who ultimately suffered graft failure in the treatment cohort was 3.3x ULN (range, 0.7-157.8) compared to a median of 2.2x ULN (range, 0.3-30.4) in subjects who had signs of graft failure but did not suffer graft failure (p=0.24). Eleven patients received prophylactic EMA based on a prior history of graft failure or other pre-transplant risk factors. EMA was well tolerated in these patients and 91% (10/11) of patients engrafted while one patient with prior history of graft failure suffered recurrent graft failure. The pre-HSCT (day -2) CXCL9 level in the lone prophylactic patient who suffered graft failure was 4x the ULN. Conclusions: This study reports the largest cohort of HSCTs that used EMA therapy for the novel purpose of treating or preventing graft failure. EMA was well tolerated in all patients. Efficacy conclusions are preliminary and limited by the study design, however our treatment study successfully identified a cohort of patients with a markedly high graft failure rate (44%) and we show preliminary evidence to suggest emaplaumab prevented graft failure in patients who had signs of impending graft failure at the time of treatment. The safety and preliminary efficacy observations in this study support a larger prospective study of IFNγ blockade for graft failure prevention after HSCT.

Benefit of living donor liver transplantation in graft survival for extremely high model for end-stage liver disease score ≥35.

Living liver donation with high model for end-stage liver disease (MELD) score was discouraged despite organ shortage. This study aimed to compare graft survival between living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) recipients with extremely high-MELD (score of ≥35). Between 2008 and 2018, 359 patients who underwent liver transplantation with a MELD score ≥35 were enrolled. We compared graft survival between LDLT and DDLT after propensity score matching (PSM) and performed subgroup analysis according to donor type. After PSM, there was no statistical difference in graft survival between the LDLT and DDLT groups (p = .466). Old age, acute on chronic liver failure, re-transplantation, preoperative intensive care unit stay and red blood cell (RBC) transfusion during the operation were risk factors for graft failure (p = .046, .005, .032, .015 and .001, respectively). Biliary complications were more common in the LDLT group (p = .021), while viral infection, postoperative uncontrolled ascites, and postoperative hemodialysis were more common in the DDLT group (p = .002, .018, and .027, respectively). In the LDLT group, acute chronic liver failure, intraoperative RBC transfusion, and early postoperative complications were risk factors for graft failure (p = .007, <.001, and .001, respectively). Our study showed that LDLT is not inferior to DDLT in graft survival if appropriate risk evaluation is performed in cases of extremely high-MELD scores. This result will help overcome organ shortages in high-MELD liver transplantation.

Indications, techniques, and graft survival of mini and corneo-scleral tectonic keratoplasties: A retrospective single-center case series.

Tectonic keratoplasties (TK) are used to treat corneal and scleral perforations and to prevent the loss of the eye. In this study, we retrospectively analyzed indications, surgical procedures, and outcomes of eccentric mini and corneo-scleral tectonic keratoplasties with respect to anatomical survival and clear graft survival rates to identify risk factors for graft failure. This retrospective study includes 33 eccentric mini (graft diameter <6 mm) and/or corneo-scleral TK of 32 consecutive patients of a total of 41 TK carried out between 2005 and 2020 in the Eye Center, University of Freiburg, Germany, making up 0.7% of all keratoplasties performed during this period (n = 5557). Patient and graft specific data were extracted from medical files. Anatomical survival-defined as achieving integrity of the globe without further surgical interventions-and clear graft survival-defined as persisting graft clarity-were estimated using the Kaplan-Meier method. We also fitted Cox proportional hazard models to account for factors influencing anatomical and clear graft survival. Median duration of anatomical success was 72.5 months (95% confidence interval (CI) 18.1-infinite (inf.)) and median duration of clear graft survival was 29.6 months (95% CI 12.5-Inf.). The 1-year survival rate for anatomical survival was 67.6% (95% CI 52.2% - 87.6%) and for clear graft survival 66.4% (95% CI 50.5%- 87.1%). No enucleation was necessary during this time-period. Non-inflammatory primary causes (n = 14) presented a trend towards better anatomical survival rates (median remained above 0.75 during follow-up) compared to inflammatory primary causes (n = 19, median 18.1 months (95% CI 2.8 - inf.)) and longer clear graft survival (median 29.6 months (95% CI 12.5 - inf.) versus 13.1 months (95% CI 3.2 - inf.)). Corneo-scleral grafts (n = 18) compared to corneal grafts (n = 15) showed a trend towards better anatomical survival (more than 50% of eyes did not fail during follow-up period (95% CI 21.9-Inf. months) versus 18.1 months (95% CI 2.4-Inf.)) and clear graft survival (median 29.6 months (95% CI 12.6-Inf.) versus 6.2 months (95% CI 2.8-Inf.)). Old age (n = 11, 75.2 - 90.1 years) compared to young age (n = 11, 6.2 - 60.2 years) was the only hazard ratio (hazard ratio 0.04 (95% CI 0.002-0.8)) that reached the level of significance (p = 0.03). Eccentric TK is helpful in the successful treatment of a variety of severe eye diseases. Patients at young age, with pre-existing inflammatory conditions or corneal TK are at higher risk for anatomical failure as well as clear graft failure and therefore need to be monitored closely.

Outcomes of pediatric deceased donor kidney transplant in northeast Thailand.

Kidney transplantation (KT) is the best therapy in children with end-stage renal disease (ESRD), however, improving long-term graft survival remains challenging. The aim of this study was to determine graft survival and potential risk factors in pediatric patients who undergo deceased donor KT with a steroid-based regimen. The medical records of children who underwent their first deceased donor KT in Srinagarind Hospital (Khon Kaen, Thailand) between 2001 and 2020 were reviewed. Seventy-two patients were studied. Male adolescents were the predominant recipients and the majority of donors were young adult males. Non-glomerular disease, particularly hypoplastic/dysplastic kidney disease, was the major cause of ESRD (48.61%). The mean cold ischemic time (CIT) was 18.29 ± 5.29h. Most of the recipients had more than 4 human leukocyte antigen (HLA) mismatched loci with positive HLA-DR mismatch (52.78%). Induction therapy was administered in 76.74% of recipients. Tacrolimus plus mycophenolate sodium and prednisolone was the most common immunosuppressive maintenance regimen (69.44%). Graft failure occurred in 18 patients, mostly due to graft rejection (50%). Graft survival at 1, 3, and 5 years after KT were 94.40%, 86.25%, and 74.92%, respectively. The only significant risk factor of graft failure in this study was delayed graft function (DGF) (adjusted HR=3.55; 95%CI: 1.14, 11.12; p=.029). Patient survival at 1, 3, and 5 years was 100%, 98.48%, and 96.19%, respectively. The short-term outcomes of pediatric KT from deceased donors were satisfactory; however, prevention of DGF would result in better outcomes.

Femoral-Physeal-Sparing ACL Reconstruction With Lateral Extra-articular Tenodesis and Inside-Out Repair of Lateral Meniscus in a Skeletally Immature Patient

Background: Anterior cruciate ligament (ACL) reconstructions in skeletally immature patients have an increased risk of graft failure and a decreased rate of successful return to sports. Anterior cruciate ligament reconstructions (ACLRs) combined with lateral extra-articular tenodesis (LET) procedures are reported to limit anterolateral rotary instability of the knee, decreasing tension on the ACL graft. However, the open physes found in pediatric patients present unique challenges for ACLR. This video demonstrates a technique to avoid the femoral physis and necessary precautions for performing an ACLR with LET in a skeletally immature patient. Indications: The indications for combined ACLR and LET, as opposed to ACLR alone, mainly center on the risk factors for graft failure. These include the following: posterior tibial slope &gt;12°, revision ACLR, high-grade pivot shift on physical examination, meniscal deficiency, generalized ligamentous hyperlaxity, and—especially pertinent to this procedure—skeletally immature patients. Technique Description: Standard plain radiographs and long-leg alignment films, along with a magnetic resonance imaging (MRI) study, are necessary to assess for malalignment, bone age, and concomitant meniscal and chondral pathology. This technique describes the senior author’s preferred technique for pediatric ACLR with LET. The senior author’s preferred order of operations includes performing the autologous hamstring graft harvest and LET before performing the diagnostic arthroscopy. This is followed by the intra-articular work including the ACLR. It is also the senior author’s preference to perform physeal-sparing femoral tunnels, using fluoroscopy for tunnel placement. Results: Getgood et al reported that an ACLR with an LET in young patients with a high risk of graft failure had a significant reduction in graft rupture compared to an ACLR alone. Furthermore, Noyes et al reported a significantly lower rate of graft failure and a higher rate of return to sports in those who received LET in addition to ACLR compared with those who received ACLR alone. Discussion: An ACLR combined with an LET has been reported to reduce graft failure rates and improve clinical outcomes in high-risk patients. An ACLR with LET may also be considered in skeletally immature patients with appropriate indications and extra precautions to avoid growth arrest or deformity. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Risk factors for failure of pre-cut eye bank UT-DSAEK grafts

The main risk factors for graft failure in penetrating keratoplasty are well known. However, few studies have examined donor characteristics or more precise data on endothelial keratoplasty. This was a retrospective, single-center study at the Nantes University Hospital, aiming to identify factors predictive of one-year success or failure of eye bank UT-DSAEK endothelial keratoplasty grafts prepared between May 2016 and October 2018. The outcome measure was success or failure at 12months post keratoplasty. One hundred and five grafts were included: 93 successes and 12 failures at 12months. The failure rate was higher in 2016 compared to 2017 and 2018. The characteristics associated with higher failure rate wereelderly donor, shorter time between harvesting and grafting, lower endothelial cell density, significant pre-graft endothelial cell loss, re-graft for Fuchs dystrophy, history of corneal transplant. Our results are consistent with those in the literature. However, some factors, such as the type of corneal harvesting or pre-graft endothelial cell loss, were not found. UT-DSAEK has demonstrated better results than DSAEK, but still appears to be somewhat inferior to DMEK. The main factor for graft failure in our study was an early re-graft within 12months. However, the low incidence of graft failure limits interpretation of these results.