Pretransplant Risk Assessment Research Articles

Influence of comorbidities on outcome in 1102 patients with an allogeneic hematopoietic stem cell transplantation.

The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to qualify comorbidities to predict non-relapse mortality (NRM) of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). HSCT procedures continue to improve. Therefore, the predictive value of HCT-CI needs to be re-evaluated. Our study is a retrospective analysis of pre-existing comorbidities assessing the relevance of the HCT-CI on the outcome of consecutive patients (n = 1102) undergoing allo-HSCT from 2006-2021. HCT-CI was classified as low (HCT-CI 0), intermediate (HCT-CI 1-2) and high-risk (HCT-CI ≥ 3). At 10 years, NRM for low, intermediate, and high-risk HCT-CI group was 21.0%, 26.0%, and 25.8% (p = 0.04). NRM difference was significant between low to intermediate (p < 0.001), but not between intermediate to high-risk HCT-CI (p = 0.22). Overall survival (OS) at 10 years differed significantly with 49.9%, 39.8%, and 31.1%, respectively (p < 0.001). In multivariate analysis of HCT-CI organ subgroups, cardiac disease was most strongly associated with NRM (HR = 1.73, p = 0.02) and OS (HR = 1.77, p < 0.001). All other individual organ comorbidities influenced NRM to a lesser extent. Further, donor (HR = 2.20, p < 0.001 for unrelated and HR = 2.17, p = 0.004 for mismatched related donor), disease status (HR = 1.41, p = 0.03 for advanced disease) and previous HSCT (HR = 1.55, p = 0.009) were associated with NRM. Improvement in transplant techniques and supportive care may have improved outcome with respect to comorbidities.

Pediatric adapted risk index to predict 2-year transplant-related mortality post-HSCT in children

AbstractSeveral attempts have been made to optimize pretransplant risk assessment to improve hematopoietic stem cell transplantation (HSCT) decision-making and to predict post-HSCT outcomes. However, the relevance of pretransplant risk assessment to the pediatric population remains unclear. We report the results of revalidation of the hematopoietic cell transplantation comorbidity index (HCT-CI) in 874 children who received 944 HSCTs for malignant or nonmalignant diseases at a single center. After finding the HCT-CI invalid in our patient population, we proposed a modified pediatric adapted scoring system that captures risk factors (RFs) and comorbidities (CoMs) relevant to pediatrics. Each RF/CoM was assigned an integer weight based on its hazard ratio (HR) for transplant-related mortality (TRM): 0 (HR < 1.2), 1 (1.2 ≥ HR < 1.75), 2 (1.75 ≥ HR < 2.5), and 3 (HR ≥ 2.5). Using these weights, the pediatric adapted risk index (PARI) for HSCT was devised, and patients were divided into 4 risk groups (group 1: without RF/CoM; group 2: score 1-2; group 3: score 3-4; and group 4: score ≥5). There was a linear increase in 2-year TRM from group 1 to 4 (TRM, 6.2% in group 1, 50.9% in group 4). PARI was successfully validated on an internal and external cohort of pediatric patients. Comparing models using c-statistics, PARI was found to have better performance than HCT-CI in predicting 2-year TRM in children, with Akaike and Schwarz Bayesian information criteria values of 1069.245 and 1073.269, respectively, using PARI, vs 1223.158 and 1227.051, respectively, using HCT-CI. We believe that PARI will be a valuable tool enabling better counseling and decision-making for pediatric patients with HSCT.

Latent Tuberculosis Infection Management in Solid Organ Transplantation Recipients: A National Snapshot.

Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Turkey. Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n= 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines.

Early Graft Failure After Living-Donor Liver Transplant.

Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.

SVEGF-R1 in acute non-infectious toxicity syndromes after pediatric allogeneic hematopoietic stem cell transplantation

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute non-infectious toxicities, including sinusoidal obstruction syndrome (SOS), engraftment syndrome (ES) and capillary leak syndrome (CLS) among others. These complications are thought to be driven by a dysfunctional vascular endothelium, but the pathophysiological mechanisms remain incompletely understood, and the diagnoses are challenged by purely clinical diagnostic criteria that are partly overlapping, limiting the possibilities for progress in this field. There is, however, increasing evidence suggesting that these challenges may be met through the development of diagnostic biomarkers to improve diagnostic accuracy of pathogenetically homogenous entities, improved pre-transplant risk assessment and the early identification of patients with increased need for specific treatment. Soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) is emerging as an important biomarker of endothelial damage in patients with trauma and sepsis but has not been studied in HSCT. ObjectivesTo investigate sVEGF-R1 as a marker of endothelial damage in pediatric HSCT patients by exploring associations with SOS, CLS, ES, and acute graft-versus-host disease (aGvHD). MethodsWe prospectively included 113 children undergoing myeloablative HSCT and measured sVEGF-R1 in plasma samples obtained weekly during the early period of transplantation and 3 months post-transplant. ResultsAll over, sVEGF-R1 levels were significantly increased from day +7 after graft infusion, peaking at day +30, most pronounced in patients receiving busulfan. Patients considered to be at increased risk of SOS and therefore commenced on prophylactic defibrotide had significantly elevated levels of sVEGF-R1 before start of conditioning (446 pg/mL vs. 281 pg/mL, p = 0.0035), and this treatment appeared to stabilize sVEGF-R1 levels compared to patients not treated with defibrotide. Thirteen (11.5%) children meeting the modified Seattle criteria for SOS at median day +8 (1–18), had significantly elevated sVEGF-R1 levels on day +14 (489 pg/mL vs. 327 pg/mL, p = 0.007). In contrast. sVEGF-R1 levels in the much broader group of patients (45.1%) meeting EBMT-SOS criteria, including patients with very mild disease, did not overall differ in sVEGF-R1 levels, but higher sVEGF-R1 levels were seen in EBMT-SOS patients with an increased need for diuretic treatment. Importantly, sVEGF-R1 levels were not associated with ES and CLS but were significantly increased on day +30 in patients with grade III-IV aGvHD (OR = 4.2 pr. quartile, p = 0.023). ConclusionVEGF-R1 levels are found to be increased in pediatric patients developing SOS, reflecting the severity of morbidity. sVEGF-R1 were unassociated with both CLS and ES. The potential of sVEGF-R1 as a clinically useful biomarker for SOS should be further explored to improve pre-transplant SOS-risk assessment, SOS-severity grading, and to guide treatment.

Leukemic Stem Cells (LSCs) As Peri-Transplant MRD Assessment in AML Patients Undergoing Allogeneic Stem Cell Transplantation in CR

Background: Several studies have shown that the leukemic stem cells (LSCs: CD34 +CD38 -CD45RA +/Combi-6 +) play a crucial role in the development of relapses in AML patients (pts). LSCs are less sensitive to conventional therapy; moreover, their phenotypical characteristics may allow immune evasion promoting relapses after allo-SCT. Although ELN guidelines recommend including LSCs into MRD assessment, this approach has not yet been studied extensively in the allogeneic setting. Here we suggested that peri-transplant LSCs detection may provide additional prognostic information to conventional (c)MRD in AML pts allografted in CR. Methods: 90 pts (male, n=46; median, 60.5 years, 19-76) with AML in CR and available pre-transplant cMRD data (multicolor flow cytometry, “different from normal” approach, according to ELN guidelines), who received allografts (matched, n=73; mismatched, n=17) during 2019-2022 years at the Department of Stem Cell Transplantation at University Medical Centre Hamburg were included. LSCs were assessed according to Zeijlemaker et al. 2019 before and after transplant at days +30 and +100. Both methods (cMRD and LSCs detection) were investigated solely and combined for their prognostic impact. Results: Majority of pts had de novo AML (76%), adverse ELN risk (48%), received matched grafts (related, n=73, 81%; unrelated, n=17, 19%) and MAC regimen (n=55, 61%). ATG was used for GvHD prophylaxis in 70 pts (78%). There were 47 cMRD neg (52%) and 43 cMRD pos (48%) pts. LSCs were detected in 39 (56%) pts with a median proportion of 0.01% (0.005-0.37%) of WBC. There was no correlation between LSCs proportion and cMRD status. The cMRD pos pts were more frequently LSCs pos (67% vs 33%), and cMRD neg were more frequently LSCs neg (33% vs 67%, p=0.002). Before allo-SCT, 34 pts (38%) were cMRD neg/LSCs neg, 26 pts (29%) experienced cMRD pos/LSCs pos, 17 pts (19%) had cMRD neg/LSCs pos and 13 pts (14%) had cMRD pos/LSCs neg. The conformity between both assays was 67%. During a median follow up of 10 months (1-29) there were 17 mortalities, 13 relapses and 11 NRM events. The 1-year OS and LFS were significantly better in LSCs neg than in LSCs pos pts: 91% (77-97%) vs 73% (55-86%, p=0.012) and 88% (72-96%) vs 52% (35-68%, p=0.001), respectively. This was due to a higher relapse rate in LSCs pos group: 33% (18-52%) vs 4% (1-20%, p=0.002). The median time to relapse was 180 days (40-395). The difference in NRM was not significant. The area under the ROC curve for relapses was 0.74 (0.61-0.88, p=0.006). Regarding the combined used of LSCs/cMRD, the best 1-year OS (p=0.038) and LFS (p=0.002) were observed for the double negative group: 94% (77-99%) and 88% (65-97%); followed by cMRD pos/LSCs neg: 86% (59-96%) and 86% (61-97%); cMRD neg/LSCs pos: 77% (43-94%) and 71% (39-90%); and the double positive group: 63% (43-79%) and 42% (25-61%)., respectively ( Figure 1). This was due to in the differing relapse rate that was highest in cMRD neg/LSCs pos group: 47% (17-79%), followed by double positive: 29% (14-50%), double negative: 7% (1-32%), and cMRD pos/LSCs neg group: 0% (p=0.02). Post-transplant cMRD/LSCs data on days +30 and +100 were available in 70 consecutive pts. The post-transplant conversion rates (positive &amp;gt; negative) for LSCs, cMRD and cMRD/LSCs were 49%, 61%, and 63%, respectively. The majority of pts converted at day +30. We observed a higher conversion rate to LSC neg status after MAC vs RIC (12/16, 75% vs 5/11, 45%, p=0.12). Of nine pts who were MRD pos at day +30, six were LSC neg and three were LSC pos. One MRD pos/LSC neg pts died due to NRM while remaining five pts survived without relapse. All three MRD pos/LSC pos pts developed relapses with two mortalities. Conclusion: Peri-transplant detection of LSCs has a strong predictive value for early post-transplant relapses in AML pts. This approach can improve pre-transplant risk assessment for cMRD pos patients by defining a population with better survival and low relapses (cMRD pos/LSCs neg) and one with worse survival and more relapses (cMRD pos/LSCs pos). The post-transplant clearance of residual disease is associated with better survival regardless of the flow strategy being used (cMRD, LSCs, or both). Pts with persisting cMRD early after allo-SCT may be subdivided into different risk groups according to their LSCs status. Figure 1. Leukemia-free survival according to pre-transplant cMRD/LSCs status in 90 AML patients.

Pretransplant immunologic risk assessment in high baseline ABO antibody titers and donor-specific anti-human leukocyte antigen antibodies in ABO incompatible kidney transplantation

Pretransplant immunologic risk assessment in high baseline ABO antibody titers and donor-specific anti-human leukocyte antigen antibodies in ABO incompatible kidney transplantation

The Role of Pre-bone Marrow Transplantation Pulmonary Function Test in Predicting Post-transplant Noninfectious Pulmonary Complications

Background: Pulmonary function test (PFT) is used as a tool for pre-transplant risk assessment and as a predictor of post-transplant outcomes. As there are currently few studies that discuss the role of PFT in bone marrow transplantation (BMT) patients in Saudi settings, and as the number of transplant patients with benign and malignant conditions continues to increase, this study was conducted with the aim of assessing the local practice. Methods: This retrospective cohort study included all adult patients who underwent BMT at Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, between 2014 and 2020. The association between established patient-related risk factors and the incidence of pulmonary complications among autologous and allogeneic groups was assessed. Results: A total of 186 patients were included (autologous = 143; allogenic = 43), of which 115 (61.8%) were male. At the pre-BMT phase, about 30% of the patients had comorbidities and 51% had received two rounds of salvage chemotherapy, while 16.1% had received radiation therapy. In the autologous group, the only PFT parameter that was a significant predictor of post-BMT pulmonary complications was forced vital capacity &lt;80% (P = 0.012), while in the allogenic group, no parameter was significantly associated with pulmonary complications. The patient-related factors that were associated with respiratory distress in the autologous group were lung involvement (P = 0.03) and pre-transplant radiation (P = 0.044). Conclusion: The findings of this study indicated that forced vital capacity &lt;80% was a significant factor in predicting non-infectious complications in the autologous group. Furthermore, lung involvement and pre-transplant radiation were the patient-related factors associated with pulmonary complications.

Clinical Decision Support Systems Used in Transplantation: Are They Tools for Success or an Unnecessary Gadget? A Systematic Review

Although clinical decision support systems (CDSSs) have been used since the 1970s for a wide variety of clinical tasks including optimization of medication orders, improved documentation, and improved patient adherence, to date, no systematic reviews have been carried out to assess their utilization and efficacy in transplant medicine. The aim of this study is to systematically review studies that utilized a CDSS and assess impact on patient outcomes. A total of 48 articles were identified as meeting the author-derived inclusion criteria, including tools for posttransplant monitoring, pretransplant risk assessment, waiting list management, immunosuppressant management, and interpretation of histopathology. Studies included 15 984 transplant recipients. Tools aimed at helping with transplant patient immunosuppressant management were the most common (19 studies). Thirty-four studies (85%) found an overall clinical benefit following the implementation of a CDSS in clinical practice. Although there are limitations to the existing literature, current evidence suggests that implementing CDSS in transplant clinical settings may improve outcomes for patients. Limited evidence was found using more advanced technologies such as artificial intelligence in transplantation, and future studies should investigate the role of these emerging technologies.

The Halifax flow Crossmatch Protocol Results According to the HLA Class and MFI of the DSA

Introduction: The main strategy to reduce the immunogenicity of transplanted grafts is to seek maximum compatibility between alloantigens in the donor-recipient pair. It is understood that the virtual crossmatch (VXM) can be a good tool in the evaluation of the donor / recipient pair and that a broader application of these protocols will improve the pre-transplant immunological risk assessment. The aim of this study was to correlate the physical flow crossmatches results, looking at different mean fluorescence intensity (MFI) values of the donor specific antibodies (DSA), and the probability of a positive crossmatch. We also aimed to validate this tool using a well standardized flow crossmatch protocol. Methods: We performed a total of 15,217 FCXM between 2015 and 2019. All were tested by the Halifax Flow Cytometer Crossmatch (FCXM) protocol, with cells from deceased donors and serum from renal recipients. For this analysis we selected only samples that had one or two DSA per locus (N = 1,081), when the MFI was above 1,000, and they were divided according to the allelic group recognized by the antibody (anti-HLA-A, B, C, DR or DQ) looking at the probability of a positive crossmatch with different MFI values of the DSAs. Combinations among them were also analyzed in the same way (N=175). Results: In the presence of an exclusive DSA against the allelic groups A, B and DR, with an index MFI above 5,000, all the FCXM were positives. With exclusively antibodies against groups C or DQ, all cases with DSAs above 15,000 MFIs were positives. With two or more DSAs anti A and/or B, and/or DR, when their MFIs sums exceeded 5,000, all FCXM results against B cells were positive. The presence of anti-Class I DSAs (A, B and A+B), regardless of the MFI value, was responsible for 71% (N=424 of 601) of the T cell positivity and 77% (N=460 of 661) in the B cell crossmatches. The presence of only anti-Class II DSAs (DR and DQ) accounted for 55% (N=168 of 303) of FCXM positivity in B cells. The overall mean of the MFI of the DSAs was higher in the FCXM positive group when compared to negative crossmatch. The group with sum of DSAs A (N=217) showed that when the sum was 4,000 MFI or higher, there was a 24 times higher probability for a positive B cell crossmatch when compared with lowers MFIs. Conclusions: Our results show a strong association between the DSA MFI and the FCXM result. The data here presented confirm the results of our previous studies, justifying the VXM standard used by our center, proving to be a good tool to streamline the selection of transplant recipients and facilitate the sharing of organs from national donors.

The Influence of Antibodies against Angiotensin II Type-1 Receptor on the Outcome of Kidney Transplantation: A Single-Center Retrospective Study.

Allo- and autoimmune mechanisms are involved in kidney allograft rejection and loss. This study investigates the impact of anti-angiotensin II type-1 receptor antibodies (anti-AT1RAbs) detected alone or in association with HLA donor-specific antibodies (HLA-DSAs) on the outcome of kidney transplantation (KTx). Anti-AT1RAbs and HLA-DSAs were detected in 71 kidney transplant (KT) recipients who developed biopsy-proven acute or chronic active T-cell rejection (TCMR) (n = 51) or antibody-mediated rejection (ABMR) (n = 20), forming the rejection group (RG). The control group (CG) included 71 KTx recipients with comparable characteristics without rejection. All patients had been transplanted with negative T/B flow crossmatch (T/BFCXM). The median follow-up period was 3.7 years. Antibodies were determined pre- and periodically post-KTx by Luminex method for HLA-DSAs and enzyme-linked immunosorbent assay for anti-AT1RAbs. Before KTx, twenty-three (32.4%) patients in the RG, sixteen with TCMR and seven with ABMR, were found anti-AT1Rabs-positive (≥10 U/mL) versus eleven (15.5%) patients in the CG (p = 0.031). Simultaneous detection of preformed anti-AT1RAbs and HLA-DSAs was found in five patients of the RG versus two of the CG (p = 0.355). At the time of transplant biopsy, fifteen (21.1%) patients, four with ABMR and eleven with TCMR, were positive for anti-AT1RAbs. Anti-AT1RAbs and HLA-DSAs were detected simultaneously in 7/15 (46.7%) cases, three with ABMR and four with TCMR. During the follow-up, thirteen (18.3%) patients in the RG, eight with ABMR and five with TCMR, lost their graft compared to one patient (1.4%) in the CG (p = 0.001). Six out of thirteen (46.2%) RG patients who lost the graft were found positive for anti-AT1RAbs pretransplant. Patient survival with functioning graft did not differ significantly between anti-AT1Rabs-positive and negative KT recipients (log-rank p = 0.88). Simultaneous detection of anti-ATR1Abs and HLA-DSAs did not have a significant influence on patient survival with functioning graft (log-rank p = 0.96). Graft function at the end of the follow-up was better, but not significantly, in anti-AT1Rabs-negative patients, with serum creatinine 1.48 [1.20-1.98] mg/dL and eGFR (CKD-EPI) 48.5 [33.5-59.0] mL/min/1.73 m2, compared to anti-AT1Rabs-positive ones who had serum creatinine 1.65 [1.24-2.02] mg/dL (p = 0.394) and eGFR (CKD-EPI) 47.0 [34.8-60.3] mL/min/1.73 m2 (p = 0.966). Anti-AT1RAbs detection pretransplant characterizes KT recipients at increased risk of cellular or antibody-mediated rejection. Furthermore, anti-AT1RAbs, detected alone or simultaneously with HLA-DSAs, appear to be associated with impaired graft function, but their role in graft survival has not been documented in this study. Screening for these antibodies appears to complement pretransplant immunological risk assessment.

Health-Related Quality of Life in Double Umbilical Cord Blood versus Haploidentical Marrow Transplantation: A Quality of Life Analysis Report of BMT CTN 1101

The Blood and Marrow Transplant Clinical Trials Network study 1101 (BMT CTN 1101; ClinicaTrials.gov identifier NCT01597778) was a multicenter phase III randomized trial comparing the clinical outcomes and quality of life (QoL) of patients with hematologic malignancies undergoing double umbilical cord blood transplantation (dUCBT) or HLA-haploidentical bone marrow transplantation (haplo-BMT) after reduced-intensity conditioning. At a 5-year follow-up, there were no significant differences in progression- free survival (PFS) or overall survival (OS) between the 2 cohorts. The impact of alternative donor source on QoL is unknown, however. English- and Spanish-speaking patients completed the Functional Assessment of Cancer Therapy-General (FACT-G), Short Form 36 (SF-36), EuroQoL-5 Dimensions EQ-5D, and Global QoL patient-reported outcome (PRO) assessments pretransplantation and at 12 and 24 months post-transplantation. We compared longitudinal QoL measures between the dUCBT and haplo-BMT cohorts and investigated the association of QoL and clinical outcomes using an inverse probability weighted-independent estimating equations method, accounting for missingness and baseline variables. We found no significant differences between the 2 cohorts in any of the QoL scores pretransplantation and at 12 and 24 months post-transplantation. Pretransplantation scores were the only significant predictors of post-transplantation QoL scores. Relapse and grade III-IV acute graft-versus-host disease (GVHD) were associated with significant declines in mean FACT-BMT and SF-36 Physical Component scores, and chronic GVHD was associated with a decline in mean EQ-5D utility scores. There were no significant associations between pretransplantation QoL scores and OS or PFS. Donor type did not impact post-transplantation QoL. Pretransplantation QoL scores and clinical events of GVHD and relapse were the only predictors of post-transplantation QoL. QoL was not associated with survival in either treatment arm. PROs may be valuable tools in pretransplantation risk assessment strategies to improve QoL outcomes.

A pre-transplantation risk assessment tool for graft survival in Dutch pediatric kidney recipients.

A prediction model for graft survival including donor and recipient characteristics could help clinical decision-making and optimize outcomes. The aim of this study was to develop a risk assessment tool for graft survival based on essential pre-transplantation parameters. The data originated from the national Dutch registry (NOTR; Nederlandse OrgaanTransplantatie Registratie). A multivariable binary logistic model was used to predict graft survival, corrected for the transplantation era and time after transplantation. Subsequently, a prediction score was calculated from the β-coefficients. For internal validation, derivation (80%) and validation (20%) cohorts were defined. Model performance was assessed with the area under the curve (AUC) of the receiver operating characteristics curve, Hosmer-Lemeshow test and calibration plots. In total, 1428 transplantations were performed. Ten-year graft survival was 42% for transplantations before 1990, which has improved to the current value of 92%. Over time, significantly more living and pre-emptive transplantations have been performed and overall donor age has increased (P<.05).The prediction model included 71829 observations of 554 transplantations between 1990 and 2021. Other variables incorporated in the model were recipient age, re-transplantation, number of human leucocyte antigen (HLA) mismatches and cause of kidney failure. The predictive capacity of this model had AUCs of 0.89, 0.79, 0.76 and 0.74 after 1, 5, 10 and 20years, respectively (P<.01). Calibration plots showed an excellent fit. This pediatric pre-transplantation risk assessment tool exhibits good performance for predicting graft survival within the Dutch pediatric population. This model might support decision-making regarding donor selection to optimize graft outcomes. ClinicalTrials.gov Identifier: NCT05388955.

Predicting psychosocial risk in pediatric kidney transplantation: An exploratory cluster analysis of a revised Pediatric Transplant Rating Instrument

The Pediatric Transplant Rating Instrument (P-TRI) is a 17-item scale developed to assess psychosocial risk factors for poor outcomes after solid organ transplantation. Research has identified the limitations of the original instrument and proposed revisions to improve clinical utility. This project examined patterns of risk in children being evaluated for kidney transplant using a revised P-TRI. A multidisciplinary kidney transplant team revised the P-TRI. A social worker and a psychologist collaboratively completed the modified instrument for 37 children after the psychosocial pretransplant evaluation. Electronic medical records were reviewed for transplant status (transplanted, active waitlist, inactive) 1 year later. Exploratory cluster analyses and chi-square tests examined patterns of risk and correlates with cluster membership. Three clusters were identified. The high-risk group (29.7%) had difficulties with medication and appointment adherence, strained relationships with the medical team, and the presence of parent psychiatric history. The medium-risk group (35.1%) had difficulties with parent knowledge, financial strain, and risk factors for medication nonadherence. The low-risk group (35.1%) demonstrated no difficulties with adherence or financial strain. Clusters were prospectively associated with transplant status, such that those in the high-risk group were less likely to be transplanted within 1 year post-evaluation. The revised P-TRI demonstrated good construct validity as risk level appeared to be associated with transplant listing status 1 year post-evaluation. These results suggest that standardized pretransplant psychosocial risk assessment tools may have value in optimizing transplant access if they can be paired with targeted, multidisciplinary interventions to address concerns early in the transplant process.

417.9: A Pre-transplant Risk Assessment Tool for Outcome in Pediatric Kidney Transplantation Based on a Dutch Cohort of 1415 Patients

417.9: A Pre-transplant Risk Assessment Tool for Outcome in Pediatric Kidney Transplantation Based on a Dutch Cohort of 1415 Patients

Pretransplant characteristics of kidney transplant recipients that predict posttransplant outcome.

Better characterization of the potential kidney transplant recipient using novel biomarkers, for example, pretransplant plasma endotrophin, will lead to improved outcome after transplantation. This mini-review will focus on current knowledge about pretransplant recipients’ characteristics, biomarkers, and immunology. Clinical characteristics of recipients including age, obesity, blood pressure, comorbidities, and estimated survival scores have been introduced for prediction of recipient and allograft survival. The pretransplant immunologic risk assessment include histocompatibility leukocyte antigens (HLAs), anti-HLA donor-specific antibodies, HLA-DQ mismatch, and non-HLA antibodies. Recently, there has been the hope that pretransplant determination of markers can further improve the prediction of posttransplant complications, both short-term and long-term outcomes including rejections, allograft loss, and mortality. Higher pretransplant plasma endotrophin levels were independently associated with posttransplant acute allograft injury in three prospective European cohorts. Elevated numbers of non-synonymous single-nucleotide polymorphism mismatch have been associated with increased allograft loss in a multivariable analysis. It is concluded that there is a need for integration of clinical characteristics and novel molecular and immunological markers to improve future transplant medicine to reach better diagnostic decisions tailored to the individual patient.

P1369: PRETRANSPLANT MODIFIED ENDOTHELIAL ACTIVATION AND STRESS INDEX (M-EASIX-7): A PREDICTOR OF PROGNOSIS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Background: Endothelial damage is considered to be the major underlying mechanism in the physiopathogenesis of transplant related complications including graft versus host disease (GVHD), thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS) and sepsis. A novel scoring index, Endothelial Activation and Stress Index (EASIX), is a simple method consisting of endothelial activation parameters, which was indicated to predict GVHD and posttransplant survival. Similarly, modified EASIX (mEASIX) is a marker of endothelial dysfunction and has been shown to be associated with the development of cytokine release syndrome after CAR-T cell therapy. Aims: In this study, we investigated the role of EASIX and mEASIX scores in the prediction of transplant related complications and survival in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). Methods: A total of 398 alloHCT recipients [median age: 43(17-71) years; male/female: 243/155] were included in this retrospective study. EASIX [lactate dehydrogenase (U/L) x creatinine (mg/dl) / platelets (109/L)] and mEASIX [lactate dehydrogenase (U/L) x C reactive protein (CRP) (mg/dl) / platelets (109/L)] scores were calculated on days -7, 0, +3 and +7. Statistical analysis was performed based on log2 transformed values. Patient and transplant characteristics are summarized in Table 1. Results: Median follow-up time was 573.5 (4-3877) days. Probability of OS was estimated to be 35.1% (1343 ± 351.7; 95% CI: 653.6-2032.3), while the probabilities of day-30 mortality, day-100 mortality and NRM were 6%, 12.5% and 49% respectively. In multivariate analysis EBMT score (p=0.026, HR: 1.177; 95% CI: 1.019-1.359), CRP (p=0.033, HR: 1.004; 95% CI: 1.000-1.008), EASIX-7 (p=0.042, HR: 0.182; 95% CI: 0.035-0.941) and mEASIX-7 (p=0.016, HR: 2.668; 95% CI: 1.202-5.924) were found to have significant impact on OS. The predictive effect of mEASIX-7 was confirmed for day-30 mortality (p=0.038; HR: 1.7; 95% CI: 1.030-2.805). A positive correlation was demonstrated between mEASIX-7 and SOS (p=0.013; r=0.249). On the other hand, mEASIX+7 was found to have a significant impact on the development of engraftment syndrome (p=0.028; HR: 1.403; 95% CI: 1.038-1.896), EASIX+3 on TMA (p=0.027; HR: 2.361; 95% CI: 1.100-5.066) and mEASIX0 on TMA (p=0.011; HR: 2.209; 95% CI: 1.199-4.068). Based on the optimal cutoff value of mEASIX-7 for the prediction of day-30 mortality, which was determined to be 2.71 [AUC: 0.747 (0.599-0.896);p=0.021], the study group was divided into two subgroups as low-mEASIX-7 and high-mEASIX7 groups. Probability of OS was significantly higher in the low-mEASIX-7 group compared to high-mEASIX-7 group (37% vs 25.2%; p=0.008; HR: 2.057; 95% CI: 1.208-3.504). Day-30 mortality (2.9% vs 19.4%; p=0.017; HR: 7.028; 95% CI: 1.418-34.836) and day-100 mortality (9% vs 33%; p=0.004; HR: 4.469; 95% CI: 1.619-12.336) were significantly lower in the low-mEASIX-7 group. Furthermore, the probability of NRM was significantly lower in the low-mEASIX-7 group compared to high-mEASIX-7 group (44.8% vs 61.4%; p=0.005; HR: 2.551; 95% CI: 1.318-4.941). Image:Summary/Conclusion: Pretransplant risk assessment is essential to guide the mainstays of the transplant procedure and optimize supportive care measures. In consideration with the basic role of endothelial activation in the development of life threatening complications of alloHCT, mEASIX-7 is indicated to have a predictive prognostic impact on survival and transplant related complications.

Accuracy of virtual crossmatch (VXM) prediction of physical crossmatch (PXM) results of donor specific antibody (DSA) in routine pretransplant settings–a single-center experience

BackgroundVirtual crossmatch (VXM) is a new powerful tool in pre-transplant risk assessment. However, the ability of VXM to predict physical crossmatch (PXM) results remains controversial. Our work evaluated the predictive potential of VXM results, measured by SAB (single antigen bead assay), for CDCXM (complement-dependent cytotoxicity crossmatch) and FLXM (flow cytometry crossmatch) results of DSA (donor specific antibody) in sensitized patients. MethodsIn total, 261 CDCXM and FLXM measurements were performed for 180 potential kidney transplant candidates, each with a single HLA-A, B, or -DR DSA against a potential deceased donor. Analysis was conducted with two SAB datasets of four-month distant and collected prior to and after PXM results. Optimal MFI (mean fluorescence intensity) thresholds and likelihood ratios were assigned based on low (<2000 MFI), medium (2001–5000 MFI) and high risk (>5000 MFI). The impact of VXM predictability was determined by the ROC curves comparison. In addition, inter-assay changes of MFI were evaluated. ResultsThe accuracy of VXM to predict CDCXM was inferior to that of FLXM with the AUC (area under ROC curve) of 0.644 vs. 0.849. In contrast, the initial ROC analysis showed that the VXM prediction was good for both T-FLXM with ROC value of 0.849 and by B-FLXM with ROC value of 0.706 for a single antigen of HLA-A, B, or -DR DSA. In fact, the best VXM prediction was for FLXM with good sensitivity for B-FLXM against HLA-DR-specific DSA (0.851). Similar results of VXM predictability were observed for pre- and post-crossmatch ROC curves. ConclusionVXM predictability is better for positive/negative FLXM than for positive/negative CDCXM results to evaluate a single HLA-A, B, -DR DSA disparity. This may be related to the fact that VXM and FLXM rely on binding of antibodies to beads or cells, respectively. In contrast, VXM is less predictive for CDCXM because the latter measures complement-dependent cytotoxic function. We intend expand VXM analysis to correlate their results with FLXM results to select low/medium risk patients for kidney transplantation in Poland.

Liver transplantation for Hepatocellular Carcinoma: A prognostic model incorporating pretransplant inflammatory cytokines

PurposeLiver transplantation (LT) remains an optimal treatment for selected hepatocellular carcinoma (HCC). Cytokines can be obtained by minimally invasive techniques and are associated with the development of HCC. The purpose of our investigation was to explore the prognostic value of pretransplant serum inflammatory cytokine profiles in HCC patients for LT. MethodsWe detected forty inflammatory cytokines in pre-LT serum from 42 HCC patients by using an inflammation-related antibody array. A pretransplant serum inflammatory cytokine-associated risk assessment model (pre-SCRAM) was developed and was validated in an external cohort of 213 HCC patients who underwent LT and were then followed prospectively. ResultsThe pre-LT factors independently associated with recurrence-free survival (RFS) were as follows: B-lymphocyte chemoattractant (BLC), interleukin (IL)-12p40 and maximum tumor diameter. High IL-12P40 level was associated with a significantly smaller maximum tumor diameter (p = 0.021), decreased proportion of nodules ≥ 3 (p = 0.001), lower platelet counts (p = 0.011) and lower portal vein tumor thrombus (p = 0.031). Conversely, recipients with poor BLC level had higher alpha-fetoprotein (AFP) levels (p = 0.016). Kaplan–Meier analyses revealed that high pre-LT BLC or IL-12p40 level was associated with superior RFS. The pre-SCRAM stratified recipients into three risk groups: high risk, intermediate risk and low risk. In the validation cohort, for patients in the high, intermediate, and low risk groups, the 3-year RFS rates were 29.3%, 58.7%, and 82.2%, respectively, the 3-year HCC-specific survival rates were 54.5%, 73.8%, and 86%, respectively, and the 3-year overall survival rates were 44.4%, 60.9%, and 79.9%, respectively. The pre-SCRAM model performed well and remained significant in optimizing the risk stratification of recurrence in patients beyond the Milan criteria or the AFP model. ConclusionPretransplant cytokine profiles can provide powerful prognostic information in the setting of LT for HCC. A pre-LT risk model incorporating cytokines showed excellent efficiency in recurrence prediction for HCC patients, which could ultimately stratify the prognosis in patients beyond the Milan criteria or the AFP model.

Age Adjusted Comorbidity Risk Index Does Not Predict Outcomes in an Autologous Hematopoietic Stem Cell Transplant Population

The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to prognosticate morbidity and mortality of patients undergoing allogeneic hematopoietic stem cell transplantation. Recently, the HCT-CI was updated to include an age component (HCT-CI-age). Although other studies have validated this tool in allogeneic stem cell transplant recipients, it has never been studied in an autologous transplant patient population. We retrospectively reviewed 181 patients who underwent their first autologous hematopoietic stem cell transplant. We aimed (1) to assess whether an HCT-CI score of 3 or greater is associated with greater mean transplant hospital days, greater total hospital days, or greater risk of intensive care unit (ICU) utilization and (2) whether age influences any of these responses independent of HCT-CI. There were 136 patients with an HCT-CI score of 3 or higher and 45 with a score less than 3. The length of initial transplant hospitalization in days was not statistically significant (15.6 v 16.4 days, P = 0.38). Utilizing spline modeling prediction curves, transplant hospital days were estimated to increase from a mean of 15.5 days for a patient with 4 comorbidities to a mean of 22.7 days for a patient with 8 comorbidities. Age made no significant impact on any of the outcomes. The HCT-CI, with or without age, in an autologous stem cell transplantation did not predict length of hospitalization or utilization of the ICU. Patients with higher-HCT-CI scores at baseline may incrementally utilize more resources, and this should be explored in a larger cohort population.