Receipt Of Transplant Research Articles

Health Disparities in Kidney Failure Among Patients With Autosomal Dominant Polycystic Kidney Disease: A Cross-Sectional Study

Understanding potential differences in patterns of kidney failure among patients with autosomal dominant polycystic kidney disease (ADPKD) may provide insights into improving disease management. We sought to characterize patients with ADPKD and kidney failure across different race/ethnicities. Cross-sectional study. Kaiser Permanente Southern California members diagnosed with ADPKD between January1, 2002, and December 31,2018. ADPKD. Kidney failure, dialysis, or receipt of kidney transplant. Differences in characteristics by race/ethnicity were assessed using analysis of variance F test and χ2 test. To compare the range and distribution of the average age at onset of kidney failure by race/ethnicity and sex, we used box plots and confidence intervals. Multivariable logistic regression was used to estimate OR for kidney transplant. Among 3,677 ADPKD patients, 1,027 (27.3%) had kidney failure. The kidney failure cohort was comprised of Black (n=138; 30.7%), White (n=496; 30.6%), Hispanic (n=306; 24.7%), and Asian (n=87; 23.6%) patients. Hispanic patients had the youngest mean age of kidney failure onset (50 years) compared to Black (56 years) and White (57 years) patients. Black (44.2%; OR, 0.72) and Hispanic (49.7%; OR, 0.65) patients had lower rates of kidney transplantation compared to White (53.8%) patients. Preemptive kidney transplantations occurred in 15.0% of patients. Retrospective study design and possible misclassification of ADPKD cases. Kidney function calculations were based on equations incorporating race, potentially overestimating kidney function in African Americans. The study was conducted within a single, integrated health care system in 1 geographic region and may not be generalizable to all ADPKD patients. Among a large diverse ADPKD population, we observed racial/ethnic differences in rates of kidney failure, age of kidney failure onset, and rates of kidney transplantation. Our real-world ADPKD cohort provides insight into racial/ethnic variation in clinical features of disease and potential disparities in care, which may affect ADPKD outcomes.

Multiple Myeloma Transplant: Examining the Intersection of Access, Age and Race

Introduction: Autologous Stem Cell Transplant (ASCT) is standard frontline therapy for patients newly diagnosed with Multiple myeloma (MM). Receipt of ASCT is influenced by factors such as race, age, socioeconomic status (SES), and geographic location. The degree to which these factors collectively influence MM transplant access and jointly impact overall survival is not well established. Our study aimed to assess the impact of age, race, rurality, and area-level SES on ASCT transplant receipt and overall survival following MM diagnosis. Methods: An IRB approved retrospective analysis was conducted of adult MM patients diagnosed in 1992-2020 from The Ohio State University Comprehensive Cancer Center (OSUCCC). Patients included were previously consented to the Buckeye Surveillance, Contact, and Research for Multiple Myeloma and Amyloidosis Protocol (NCT01408225); a registry database for patients with suspected plasma cell dyscrasia pursuing care at OSUCCC; and the Bone Marrow Transplant (BMT) registry, an internal database compiled of demographic and transplant-specific data. Area-level SES was measured by census tract-level (2008-2017) Yost indices (a composite of education-, income-, and occupation-related variables.)1, 2 Rural-urban status was measured by census tract-level 2010 Rural-Urban Commuting Area (RUCA) codes.3 Yost were categorized into quartiles where higher quartiles represented higher SES, and RUCA codes were grouped by metropolitan (Primary RUCA 1-3) v. non-metropolitan (Primary RUCA 4-10). Poisson regression models with robust variance were used to evaluate the associations between patient characteristics and receipt of transplant. Overall survival (OS) from diagnosis was analyzed and median OS was estimated using the Kaplan-Meier method. Cox proportional hazard models were used to estimate the hazard ratios of risk of death. Results: In the combined MM registries, a total of 1,799 MM patients were included in this analysis, 1,169 (65%) received a transplant. MM patients median age at diagnosis was 61 (17-87), race was self-identified as White (85.6%), Black (13.1%) other (1.3%). In multivariable analysis, patients who were 65 years or older were less likely to undergo a transplant (age 65-70: IRR=0.80, 95% CI: 0.72-0.89, p<0.001; age > 70: IRR 0.23, 95% CI: 0.18-0.30, p<0.001). When assessed by race, relative to White patients, Black patients were less likely to receive a MM transplant (IRR=0.85, 95% CI: 0.74-0.97, p=0.018). RUCA code showed no significant difference in receiving a transplant between the non-metropolitan v. metropolitan groupings (IRR 1.06, 95% CI: 0.97-1.16, p=0.186). Residence in higher SES areas (quartiles 2-4) was associated with higher rate of ASCT receipt compared to those in quartile 1 (IRR 1.16, 95% CI: 1.05-1.29, p=0.038). Among all MM patients median OS for age <65 was 9.0 years (95%CI 8.4-9.7); age 65-70, 7.0 years (95%CI 6.3-7.9); age>70, 4.7 years (95%CI 4.0-5.3). In multivariable analysis, hazard of death was lower for those who received a transplant (vs. no transplant, HR= 0.63, 95%CI 0.53-0.74, p<0.001), patients identified as Black (vs. White, HR=0.66, 95%CI 0.51-0.85, p=0.001), and those residing in higher SES areas (quartile 2-4 vs. quartile 1, HR=0.69, 95%CI 0.58-0.83, p<0.001). Advancing age was associated with higher hazard of death, age 65-70 HR=1.45 (95%CI 1.18-1.78, p<0.001); age >70 HR=2.03 (95%CI 1.65-2.49, p<0.001). Rurality was not associated with OS (HR 1.14, 95% CI 0.96-1.35, p=0.134). Conclusions: In a large MM population, age, race, and area-level socioeconomic status impact both the receipt of transplant and overall survival following MM diagnosis. Area-level SES could be an important driver of MM survival independent of transplant access.

Outcomes for Patients with Relapsed and Refractory Peripheral T-Cell Lymphoma in the 21st Century By Relapse Status, Salvage Therapy, and Receipt of Allogeneic Transplant

Outcomes for Patients with Relapsed and Refractory Peripheral T-Cell Lymphoma in the 21st Century By Relapse Status, Salvage Therapy, and Receipt of Allogeneic Transplant

Patient-Reported Outcome Measures in Newly Diagnosed Acute Myeloid Leukemia: An Exploratory Analysis of Real-World Data

Background: Patients with acute myeloid leukemia (AML) may experience substantial disease- and treatment-related symptoms. Patient-reported outcome (PRO) assessments are validated tools to evaluate patient symptoms and function, and are associated with improved health-related quality of life (HRQoL), reduced unplanned acute care, and longer overall survival among patients with advanced solid tumors (Basch E et al. JAMA, 2017.318(2):197-198). However, PROs are used infrequently in the AML population outside of clinical trials. Objectives: We assessed the characteristics of baseline PRO measurements in patients with newly diagnosed AML and evaluated their association with short-term acute care utilization and receipt of allogeneic hematopoietic stem cell transplantation (alloHSCT). Methods: We retrospectively identified all patients with non-M3 AML diagnosed between 6/2018 and 3/2020 who were actively receiving therapy at our institution and completed at least one outpatient PRO survey within a period of 1 month preceding to 3 months following AML diagnosis. This assessment period was selected to allow us to assess outpatient PROs, since many patients are admitted at initial presentation and remain inpatient for an extended period at the time of diagnosis. The survey completed at the time closest to the time of diagnosis was defined as baseline PRO. PROs were measured using a 14-question assessment administered before each outpatient encounter using the National Cancer Institute's PRO Version of The Common Terminology Criteria for Adverse Events. The survey addresses 9 symptom scales rated by patients on a scale of 1-5 ranging from no symptom to very severe symptom with higher scores indicating worse symptoms, and 1 QoL scale with higher scores indicating improved QoL. Time to acute care visit (TAC) was defined as the time from baseline PRO measurement to the first unplanned acute care visit (emergency room visit or unplanned hospitalization) and assessed using Kaplan-Meier survival function and log-rank test. Fisher's exact test was used to assess the associations between symptom burden and age, therapy intensity subgroups, and alloHSCT status. Results: Seventy patients with a median age of 63 years (range 22-88) at AML diagnosis were included in the analysis. The median follow-up was 19.2 months. Forty patients (57.1%) underwent intensive induction therapy, i.e., "7+3" and its variations. Thirty patients (42.9%) received non-intensive therapy, primarily venetoclax/azacitidine. The most common (n=52, 75.4%) and most severe symptom reported in our cohort was fatigue, with a mean score of 3.06 (standard deviation (SD) 1.07). Symptom burden did not differ between younger (< 60yrs (n=29, 41.4%)) and older (≥ 60yrs) patients, except for sadness which was reported more frequently in patients < 60yrs (41.4% vs. 19.5%, p=0.043). Patients undergoing non-intensive therapy reported more frequent dyspnea at baseline (61.5% vs. 37.5%, p=0.048) (table 1). Mean QoL score (2.71, SD 1.21) did not differ by age or induction intensity. The median TAC was 16.1 weeks with 60 (85.7%) patients having at least one acute care visit. Patients with moderate to severe baseline fatigue (fatigue score > 2 (n=30, 43.5%) ) had a median TAC of 13.9 weeks and tended to a higher risk of sooner acute care visit initially compared to those with none to mild fatigue (fatigue score ≤ 2) (TAC 20.4 weeks, p=0.282) (figure 1). In patients with intermediate- and adverse-risk disease (n=54), more patients with baseline fatigue score ≤ 2 (n=28, 51.9%) were able to undergo alloHSCT (53.6% vs. 28.0%, p=0.053). Additionally, lower fatigue scores on follow-up PRO survey post-induction were associated with a higher rate of alloHSCT (61.5% for patients with fatigue scores ≤ 2 vs. 24.0% with fatigue scores >2, p=0.007) despite no difference in remission status between the two groups post-first induction cycle (53.6% vs. 31.8%, p=0.182). Conclusions: In patients with newly diagnosed AML, fatigue was the most prominent symptom reported at baseline. Patients with worse baseline fatigue may be at risk for sooner unplanned acute care visits within the first year of diagnosis. Patients with less fatigue post-induction had a higher chance of undergoing alloHSCT. Further investigation is needed to better understand and utilize the real-world PRO data to help provide patient-centered, goal-concordant care to AML patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment Outcomes of Childhood Picalm:MLLT10+ Acute Leukemias: An International Retrospective Study

Introduction: Acute leukemia with translocation t(10;11)(p12-13;q14-21) results in generation of the PICALM:MLLT10 fusion gene, and is distinct from t(10;11)(p11-13;q23) which gives rise to KMT2A (formerly MLL) gene rearrangement. Defective PICALM function leads to aberrant hematopoiesis, while defective MLLT10 function impairs chromatin-mediated gene regulation. The PICALM:MLLT10 gene has been reported in patients with Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL) predominantly T-cell, Acute Undifferentiated Leukemia (AUL) and Mixed Phenotype Acute Leukemia (MPAL). MLLT10 interacts directly with DOT1L in a complex that regulates the methylation of H3K79. MLLT10 fusions are thought to misdirect DOT1L to the promoters of HOXA genes, leading to hypermethylation of H3K79. This hypermethylation causes constitutive activation of HOXA activity and prevents cell maturation and differentiation. The clinico-biological characteristics, response to conventional treatments, and survival outcomes of childhood PICALM:MLLT10+ leukemias are poorly understood. Methods: This was an international, multicenter, retrospective cohort study. Data were submitted by ten International-BFM (I-BFM) study Group-AML and ALL committees and by the Children`s Oncology Group (COG)-AML Study committee. For study inclusions, patients were required to be ≤ 21 years of age at diagnosis, diagnosed between January 1995 and December 2019 with de novo ALL, AML, AUL or MPAL and PICALM:MLLT10 fusion-positive. Patients with KMT2A-rearranged leukemia or acute promyelocytic leukemia were excluded. Kaplan Meier curves were employed for survival analysis with Cox proportional hazard modelling to compare effect of AML vs ALL therapy, and receipt of hematopoietic stem cell transplant (HSCT) vs no HSCT, on survival. Pearson's Chi Squared was employed as a non-parametric measure to determine the effect of end of induction-1 (EIO-1) MRD positive vs negative status on incidence of relapse. P value cut-off for data to reach statistical significance was <0.05. Results: Ninety-eight children with acute leukemia were included, 60 were males. Median age at diagnosis was 12 years (IQR:9-14.8 years) and median initial white cell count was 40.5 x 109/L (IQR:13.8-168.9). Fifty-five (55.6%) patients were diagnosed with T-ALL, 39 (39.4%) with AML, while precursor-B ALL, AUL and MPAL were each diagnosed in single patients; 1 subtype diagnosis was unknown. Ten (10.1%) patients presented with CNS disease and 13 (13.1%) presented with non-CNS extramedullary manifestations. Of 66 with cytogenetic/molecular data available, 33 (50%) had additional cytogenetic-molecular aberrations; NOTCH1, WT1 and RAS pathway mutations predominated. Most patients received an initial chemotherapy regimen guided by their disease immunophenotype: 58/98 (58.6%) received an ALL-like chemotherapy regimen upfront, 38 (38.4%) received an AML-like regimen, 1 (1.0%) a hybrid regimen, 1 initial chemotherapy regimen was unknown. Five-year event-free survival (EFS) was 50.4% (CI 39.1-64.9). For AML patients, 5-year EFS was 22.5% (CI 9.75-52.0) and for ALL 67.7% (CI 54.2-84.7), p=<0.001. Five-year overall survival (OS) was 56.3% (CI 46.3-68.5). For AML patients, 5-year OS was 26.7% (CI 13.3-53.6) and for ALL 75.7% (CI 64.6-88.8), p=<0.001. Thirty-eight patients died, 22 (57.9%) deaths were disease-related, 4 (10.5%) treatment-related. Patients who received HSCT in CR1, demonstrated a trend towards an inferior 5-year EFS (23.7% vs 56.5%) and OS (42.6% vs 64.5%) than those who did not; however, analysis was limited by small sample size. Four (22.2%) HSCT recipients had ALL but most, 14 (77.8%), had AML, which may account for the unfavourable outcomes associated with HSCT. There was no statistically significant difference in rate of relapse in the EOI-1 MRD-positive compared with MRD-negative patients (p=0.49). Of those who relapsed, 25 (75.8%) had an isolated bone marrow relapse, 3 (9.1%) isolated CNS, 3 (9.1%) other sites and, for 2 patients, site of relapse was unknown. Conclusions: Children with PICALM:MLLT10+ AML have inferior 5-year EFS and OS outcomes compared to their T-ALL counterparts. MRD status at EOI-1 was not predictive of relapse. Targeted therapies with DOT1L inhibitors or DNA demethylating agents should be explored, particularly for patients with AML.

Prognostic Value of Translocation 11;14 in Patients with Relapsed/Refractory Myeloma Receiving Anti-CD38 Therapy

Introduction: The translocation t(11;14) is present in ~15% of patients newly diagnosed MM and is associated with a unique clinical and pathological phenotype, despite still being classified as standard risk MM. Ex-vivo studies have also suggested that CD38 expression is decreased in patients with MM that harbors t(11;14), and hence there is a need for real-world data that compares the efficacy of anti-CD38 therapy for patients with and without t(11;14). We used clinical and cytogenetic data from a large, group of real-world patients with relapsed/refractory MM. We hypothesized that CD38 expression would be sufficient in those with t(11;14) to permit activity of anti-CD38 antibodies and that amongst patients receiving anti-CD38 therapies, outcomes would be similar in patients with t(11;14) when compared to those without the translocation. Methods: We conducted a retrospective cohort study using the Flatiron Health electronic health record (EHR)-derived database. We evaluated data from relapsed/refractory MM patients initiating treatment including anti-CD38 therapy in their 2nd or later line of therapy between November 2015 and December 2021. Patients were also required to have documented cytogenetic testing by FISH for high-risk cytogenetic abnormalities (HRCAs) and t(11;14). Presence of t(11;14) and HRCAs defined as deletion 17p, amplification or gain 1q21, t(4;14), t(14;16) and t(14;20) was determined from FISH testing. Our primary outcomes of interest were progression-free survival (PFS) and overall survival (OS). We used the Kaplan-Meier product limit estimator to calculate survivor functions for PFS and OS and compared equality of survivor functions between groups stratified by t(11;14) and HRCA status using log-rank tests. A multivariate analysis was done adjusting for age, sex, functional status, ISS Stage, eGFR and autologous stem cell transplant receipt. Separate analysis was performed for patients with just t(11;14) and no other HRCA, as well as those without (t11;14) and no HRCA (defined as wildtype). Results: An overall cohort of 1,685 patients with MM initiating anti-CD38 therapy as 2nd or later treatment with a median follow up of 22.6 months was identified. Patient characteristics are listed in Table 1. In the overall study sample, patients with and without t(11;14) had a similar median PFS, 16.6 months and 15.0 months respectively (Figure 1, p = 0.24). Median PFS was also similar when comparing patients with t(11;14) and no HRCAs (19.9 months) to wild-type patients (19.6 months) (p = 0.59). Similar associations were observed for these comparisons in OS. Median OS for patients with and without t(11;14) was 49.8 months and 31.9 months respectively (p = 0.07). In multivariable models comparing PFS in patients with t(11;14) to patients without t(11;14), we observed similar risks (HR 1.07, 95% CI 0.80-1.44, p = 0.65) after adjustment for confounders and presence of other HRCAs. When comparing PFS in patients with t(11;14) and no HRCAs to wildtype patients, no statistically significant differences were observed (HR 1.27, 95% CI 0.84-1.94, p = 0.26). In multivariable models comparing OS in patients with t(11;14) to patients without t(11;14), we observed similarly not significant risks (HR 0.82, 95% CI 0.56-1.20, p = 0.31) after adjustment for confounders and presence of other HRCAs. When comparing OS in patients with t(11;14) and no HRCAs to wildtype patients, we also observed similar risks of overall mortality (HR 0.90, 95% CI 0.50-1.61, p = 0.72). Conclusion: In this large real-world study of outcomes of anti-CD38 therapy with relapsed/refractory MM, no significant difference in outcomes were observed between those who had t(11;14) compared to those who did not. This study has important implications as t(11;14) is increasingly recognized as a unique subset of MM with different biology, treatment response rates, and prognosis. As targeted therapies specific to patients with t(11;14) such as venetoclax are increasingly utilized in this patient population, it is important to recognize that anti-CD38 therapy should remain an important part of the treatment landscape for these patients, and that synergistic strategies incorporating bcl-2 inhibition and anti-CD38 targeting should be explored further in clinical trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of Evaluations for Heart Transplant Before Durable Left Ventricular Assist Device and Subsequent Receipt of Transplant at Transplant vs Nontransplant Centers

In 2020, the Centers for Medicare & Medicaid Services revised its national coverage determination, removing the requirement to obtain review from a Medicare-approved heart transplant center to implant a durable left ventricular assist device (LVAD) for bridge-to-transplant (BTT) intent at an LVAD-only center. The association between center-level transplant availability and access to heart transplant, the gold-standard therapy for advanced heart failure (HF), is unknown. To investigate the association of center transplant availability with LVAD implant strategies and subsequent heart transplant following LVAD implant before the Centers for Medicare & Medicaid Services policy change. A retrospective cohort study of the Society of Thoracic Surgeons Intermacs multicenter US registry database was conducted from April 1, 2012, to June 30, 2020. The population included patients with HF receiving a primary durable LVAD. LVAD center transplant availability (LVAD/transplant vs LVAD only). The primary outcomes were implant strategy as BTT and subsequent transplant by 2 years. Covariates that might affect listing strategy and outcomes were included (eg, patient demographic characteristics, comorbidities) in multivariable models. Parameters for BTT listing were estimated using logistic regression with center-level random effects and for receipt of a transplant using a Cox proportional hazards regression model with death as a competing event. The sample included 22 221 LVAD recipients with a median age of 59.0 (IQR, 50.0-67.0) years, of whom 17 420 (78.4%) were male and 3156 (14.2%) received implants at LVAD-only centers. Receiving an LVAD at an LVAD/transplant center was associated with a 79% increased adjusted odds of BTT LVAD designation (odds ratio, 1.79; 95% CI, 1.35-2.38; P < .001). The 2-year transplant rate following LVAD implant was 25.6% at LVAD/transplant centers and 11.9% at LVAD-only centers. There was an associated 33% increased rate of transplant at LVAD/transplant centers compared with LVAD-only centers (adjusted hazard ratio, 1.33; 95% CI, 1.17-1.51) with a similar hazard for death at 2 years (adjusted hazard ratio, 0.99; 95% CI, 0.90-1.08). Receiving an LVAD at an LVAD-transplant center was associated with increased odds of BTT intent at implant and subsequent transplant receipt for patients at 2 years. The findings of this study suggest that Centers for Medicare & Medicaid Services policy change may have the unintended consequence of further increasing inequities in access to transplant among patients at LVAD-only centers.

Subjective cognitive complaints in end-stage renal disease: a systematic review and meta-analysis

ABSTRACT Cognitive impairment is common in patients with end-stage renal disease (ESRD) and is associated with compromised quality of life and functional capacity, as well as worse clinical outcomes. Most previous research and reviews in this area were focused on objective cognitive impairment, whereas patients’ subjective cognitive complaints (SCCs) have been less well-understood. This systematic review aimed to provide a broad overview of what is known about SCCs in adult ESRD patients. Electronic databases were searched from inception to January 2022, which identified 221 relevant studies. SCCs appear to be highly prevalent in dialysis patients and less so in those who received kidney transplantation. A random-effects meta-analysis also shows that haemodialysis patients reported significantly more SCCs than peritoneal dialysis patients (standardised mean difference −0.20, 95% confidence interval −0.38 to −0.03). Synthesis of longitudinal studies suggests that SCCs remain stable on maintenance dialysis treatment but may reduce upon receipt of kidney transplant. Furthermore, SCCs in ESRD patients have been consistently associated with hospitalisation, depression, anxiety, fatigue, and poorer quality of life. There is limited data supporting a strong relation between objective and subjective cognition but preliminary evidence suggests that this association may be domain-specific. Methodological limitations and future research directions are discussed.

Survival, response rates, and post-transplant outcomes in patients with Acute Myeloid Leukemia aged 60-75 treated with high intensity chemotherapy vs. lower intensity targeted therapy

The United States Food and Drug Administration has approved several oral, targeted therapies for the treatment of Acute Myeloid Leukemia (AML) in recent years. These agents are approved in patients with relapsed/refractory disease or as frontline therapy in patients who are ineligible for intensive chemotherapy based on age, performance status, or comorbidities. They are also being increasingly utilized frontline in patients of all ages and fitness levels through clinical trials and off label prescribing, but comparative treatment outcomes associated with intensive versus targeted therapy have not been extensively studied. We conducted a single center, retrospective analysis to address the impact of treatment intensity on survival in patients with AML aged 60-75 at diagnosis. This study included 127 patients, 73 of whom received high intensity chemotherapy at any point during treatment (any HiC) and 54 of whom received only low intensity targeted therapy (LITT only). Overall survival (OS) from treatment initiation did not differ significantly between the any HiC and LITT only groups (hazard ratio (HR) for death, 0.67; 95% CI, 0.41 to 1.09; P=0.11). The only three variables that were independently associated with superior OS were lower European Leukemia Net (ELN) risk classification, TP53 unmutated status, and receipt of transplant. Our data suggest that baseline genomic features and receipt of transplant are more important than treatment intensity in predicting survival in this patient population. They also highlight the vital role of transplant in older patients with AML regardless of treatment intensity utilized for remission induction. Larger studies are needed to further address this question, including prospective randomized trials.

Utility of geriatric assessments in evaluation of older adults for kidney transplantation.

While kidney transplantation has favorable outcomes in patients aged 65 years and older, many are not referred for evaluation despite having no contraindications. We wanted to determine whether incorporating geriatrics and geriatric assessments (GA), as part of kidney transplant evaluation at the University of Chicago Medicine, would help identify suitable candidates and improve transplantation outcomes among older adults. Between 2012 and 2016, as part of their multi-disciplinary transplant evaluation, 171 patients underwent an initial GA with the study geriatrician, who rated them on a five-point scale from "poor" to "excellent," and presented their cases to multidisciplinary transplant review meetings. Patients were followed until June 1st, 2021. Predictor variables included geriatric recommendation, clinical characteristics, and demographics. Outcomes of interest were mortality, receipt of transplant, and waitlist placement. Compared to patients rated "poor," "marginal," or "fair," we found that patients that the geriatrician recommended as "good" or "excellent" were more likely to be waitlisted and receive a transplant. Favorably rated patients were also less likely to be removed from the waitlist due to becoming medically unfit, meaning worsening medical morbidity, frailty, and cognitive status. Including geriatricians to perform GAs as part of the transplant evaluation process can help identify suitable elderly candidates.

Relationships between 2018 UNOS heart policy and transplant outcomes in metropolitan, micropolitan, and rural settings.

In 2018, United Network for Organ Sharing (UNOS) extended the radius for which a heart transplant candidate can match with a donor, and outcomes across population densities are unknown. We sought to determine whether the policy change was associated with differences in heart transplant waitlist time or death post-transplant for patients from rural, micropolitan, and metropolitan settings. Using the Scientific Registry of Transplant Recipients, we evaluated U.S. adult patients listed for heart transplant from Janurary 2017 to September 2019 with follow-up through March 2020. Patients were stratified by home zip-codes to either metropolitan, micropolitan, or rural settings. Fine and Gray and Cox models were respectively used to estimate Sub-distribution hazard ratios (SHR) of heart transplant with death or removal from transplant list as a competing event, and HR of death post-transplant within population densities after versus before the UNOS policy change date, October 18, 2018. Analyses were adjusted for demographics, comorbidities, and labs. Among 8,747 patients listed for heart transplant, 84.7% were from metropolitan, 8.6% micropolitan, and 6.6% rural settings. The 2018 UNOS policy was associated with earlier receipt of heart transplant for metropolitan [SHR 1.56 (95% CI: 1.46-1.66)] and micropolitan [SHR 1.48 (95% CI: 1.21-1.82)] populations, but not significantly for rural [SHR 1.20 (95% CI: 0.93-1.54)]; however, the interaction between policy and densities was not significant (p=.14). Policy changes were not associated with risk of death post-transplant [metropolitan: HR 1.04 (95% CI: 0.80-1.34); micropolitan: HR 1.10 (95% CI: 0.55-2.23); rural: HR 1.04 (95% CI: 0.52-2.08); interaction p=.99]. The 2018 UNOS heart transplant policy was associated with earlier receipt of heart transplant and no difference in post-transplant survival within population densities. Additional follow-up is needed to determine whether improvements are sustained.

Association Between Dialysis Facility Ownership and Access to the Waiting List and Transplant in Pediatric Patients With End-stage Kidney Disease in the US

Care of adults at profit vs nonprofit dialysis facilities has been associated with lower access to transplant. Whether profit status is associated with transplant access for pediatric patients with end-stage kidney disease is unknown. To determine whether profit status of dialysis facilities is associated with placement on the kidney transplant waiting list or receipt of kidney transplant among pediatric patients receiving maintenance dialysis. This retrospective cohort study reviewed the US Renal Data System records of 13 333 patients younger than 18 years who started dialysis from 2000 through 2018 in US dialysis facilities (followed up through June 30, 2019). Time-updated profit status of dialysis facilities. Cox models, adjusted for clinical and demographic factors, were used to examine time to wait-listing and receipt of kidney transplant by profit status of dialysis facilities. A total of 13 333 pediatric patients who started receiving maintenance dialysis were included in the analysis (median age, 12 years [IQR, 3-15 years]; 6054 females [45%]; 3321 non-Hispanic Black patients [25%]; 3695 Hispanic patients [28%]). During a median follow-up of 0.87 years (IQR, 0.39-1.85 years), the incidence of wait-listing was lower at profit facilities than at nonprofit facilities, 36.2 vs 49.8 per 100 person-years, respectively (absolute risk difference, -13.6 (95% CI, -15.4 to -11.8 per 100 person-years; adjusted hazard ratio [HR] for wait-listing at profit vs nonprofit facilities, 0.79; 95% CI, 0.75-0.83). During a median follow-up of 1.52 years (IQR, 0.75-2.87 years), the incidence of kidney transplant (living or deceased donor) was also lower at profit facilities than at nonprofit facilities, 21.5 vs 31.3 per 100 person-years, respectively; absolute risk difference, -9.8 (95% CI, -10.9 to -8.6 per 100 person-years) adjusted HR for kidney transplant at profit vs nonprofit facilities, 0.71 (95% CI, 0.67-0.74). Among a cohort of pediatric patients receiving dialysis in the US from 2000 through 2018, profit facility status was associated with longer time to wait-listing and longer time to kidney transplant.

P498: CLINICAL AND BIOLOGICAL MARKERS ASSOCIATED WITH LONG-TERM SURVIVAL FOR PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML) IN REMISSION AFTER CHEMOTHERAPY IN THE QUAZAR AML-001 TRIAL OF ORAL AZACITIDINE

Background: In the randomized, phase 3 QUAZAR AML-001 trial, oral azacitidine (Oral-AZA) significantly prolonged overall survival (OS) compared with placebo (PBO) (median OS 24.7 vs 14.8 months [mo], respectively) in older patients (pts) with AML in first remission after intensive chemotherapy (IC). At an updated data cutoff performed in Sep 2020, 34.9% of pts in the Oral-AZA arm and 24.4% of pts in the PBO arm remained alive at ≥3 y from randomization. Aims: Assess clinical and biological variables associated with long-term survival (LTS) in QUAZAR AML-001. Methods: In all, 472 pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO QD ×14d/28d within 4 mo of achieving first complete remission (CR) or CR with incomplete blood count recovery (CRi) after IC. The primary endpoint was OS, time from randomization until death, withdrawal of consent, or loss to follow-up. The LTS cohort comprised pts who were alive ≥3 y from randomization as of Sep 2020 and the non-LTS cohort included pts who died or were censored before 3 y. Variables assessed for association with LTS were diagnostic (Dx [pre-IC]) features (AML subtype, cytogenetic risk, NPM1 and FLT3 mutations [mut]); pre-study treatment (Tx) variables (response to IC [CR/CRi], receipt of consolidation, number of consolidation cycles); baseline (BL) demographic and disease characteristics, hematologic parameters (red blood cells [RBCs], hemoglobin, platelets, and leukocyte subsets), and measurable residual disease (MRD) status; and post-BL variables (MRD response [conversion from MRD+ at BL to MRD– on study], timing of MRD– [MRD– response on-study vs BL MRD–], and receipt of transplant after Tx discontinuation [D/C]). Associations of LTS with bone marrow immune parameters (CD3, CD4, and CD8 T-cell counts, and expression of PD-1/TIM-3 T-cell exhaustion markers) were investigated in a subset of pts (n=108). Variables were compared within Tx arms (LTS vs non-LTS) in univariate analyses with P values corrected for multiple testing. A logistic multivariable regression analysis of the effects of prognostic BL covariates on LTS was performed. Results: The LTS cohort included 83/238 pts (34.9%) in the Oral-AZA arm and 57/234 pts (24.4%) in the PBO arm. Within both arms, factors significantly associated with LTS were intermediate (Int)-risk cytogenetics and NPM1mut at Dx, and MRD response (MRD+ to MRD–) on study (Figure). MRD response rate was 2-fold higher with Oral-AZA vs PBO (37% vs 19%, respectively), and while early attrition was more common in the PBO arm, most MRD responses occurred within 6 mo. Factors significantly associated with LTS only in the PBO arm were BL (post-IC) MRD– status and receipt of transplant after Tx D/C. No significant associations were observed between BL hematological or immune parameters and LTS. The multivariable analysis (MVA) confirmed Oral-AZA Tx as independently significantly predictive of LTS vs PBO. Other covariates significantly associated with LTS in MVA were Int-risk cytogenetics and NPM1mut at Dx, and MRD– status at BL. Image:Summary/Conclusion: Oral-AZA Tx was significantly associated with LTS vs PBO. In univariate analysis, Int-risk cytogenetics and NPM1mut at Dx, and MRD response on-study, were significantly prognostic of LTS in both arms, whereas MRD– status at BL (post-IC) was associated with LTS only in the PBO arm.

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.

Outcomes of dialysis in neonates with anuric end-stage renal disease at birth: ethical considerations

We present a case series of neonates with anuric ESRD undergoing renal replacement therapy (RRT) and discuss the associated ethical implications of RRT in this population. We reviewed patients who initiated RRT within 1 week of life due to anuric ESRD from 2009-2019 at a single tertiary center. Primary outcomes were receipt of renal transplant (RT), one-year survival, and overall survival. Five patients met the inclusion criteria. Two patients received an RT. One-year survival was 80%, while overall survival was 60% with a median follow-up of 18 months. In the 2 still-living patients who have not undergone RT, they are ineligible, one due to recent malignancy and the other from acquired cardiovascular comorbidities. Patients with anuric ESRD requiring RRT undergo multiple treatment challenges with low RT and survival rates. These findings should be shared with families considering intervention for cases of severe renal disease diagnosed prenatally.

Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol‐related liver disease

Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings. Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use. Three hundred and seventy-five patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P<.05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR=2.86; 95%CI 1.67-4.97) CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease.

The beneficial effect of providing kidney transplantation information on transplantation status differs between for-profit and nonprofit dialysis centers.

Informing end-stage kidney disease patients about kidney transplantation options increases the likelihood of kidney transplant waiting list (WL) enrollment and live donor kidney transplant (LDKT) receipt. Patients in for-profit dialysis centers have lower rates of WL enrollment and LDKT receipt. This study examined if the ownership status of dialysis centers modified the association between informing patients about transplantation options and patients' transplantation status. Multilevel analysis using mixed-effect multinomial logistic regression was performed using the United States Renal Data System (USRDS) data (January 2005 to December 2017). The study showed that informing patients improved the odds of WL enrollment and LDKT receipt. However, the effect of informing patients on transplantation status was less pronounced at for-profit as compared with nonprofit centers (Nonprofit: WL enrollment OR: 2.23 [95% CI: 2.07-2.40], and LDKT receipt OR: 3.35 [95% CI: 2.65-4.25]. For-profit: WL enrollment OR: 1.73 [95% CI: 1.66-1.79], and LDKT receipt OR: 2.35 [95% CI: 2.08-2.66]), although the odds of informing patients was higher for for-profit centers, and type of patients informed were similar across both types of centers. Information provided by for-profit centers was potentially less effective than those provided by nonprofit centers. Standardized guidelines for transplantation information provision are needed in order to ensure similar informational quality across centers.

MELD-Na Accurately Predicts 6-Month Mortality in Patients With Decompensated Cirrhosis: Potential Trigger for Hospice Referral.

The goal of this study was to determine the accuracy of Model of End-stage Liver Disease-Sodium (MELD-Na) in predicting 6-month mortality for patients listed for liver transplantation on the United Network of Organ Sharing (UNOS) waitlist. End-stage liver disease patients underutilize hospice services despite significant morbidity and mortality associated with advanced liver disease. A well-known barrier to hospice referral is clinician uncertainty in identifying patients with an expected survival of <6 months, a requirement for a referral. Retrospective cross-sectional analysis was performed from UNOS data spanning February 27, 2002, to September 30, 2019. Inclusion criteria of patients aged 18 years and above, diagnosis of cirrhosis, liver transplant eligible, and listed in the UNOS database. Exclusion criteria included fulminant hepatic failure, prior history of liver transplantation, diagnosis of hepatocellular carcinoma, receipt of liver transplant in <180 days, or removal from waiting list <180 days for a reason other than death. Mortality by 180 days. Of the 93,157 patients that met inclusion criteria, MELD-Na was calculated for all patients with sodium, total bilirubin, international normalized ratio, and creatinine available (N=79,611). The c -statistic with 95% confidence interval for MELD-Na for the predicted 6-month mortality was 0.83 (0.827-0.835). Mean MELD-Na of 28.2 was associated with ≤50% 6-month survival. MELD-Na is an objective, quick measure that can aid providers in identifying patients with increased 6-month mortality in time-constrained settings, and a score of 28 can trigger the discussion for hospice as a means of improving value-based health care.

Effect of High Intensity Chemotherapy Vs Targeted Therapy on Survival in AML Patients Aged 60-75

Effect of High Intensity Chemotherapy Vs Targeted Therapy on Survival in AML Patients Aged 60-75

Social Deprivation Independently Predicts Survival in Younger Patients with Acute Myeloid Leukemia (Alliance)

Social Deprivation Independently Predicts Survival in Younger Patients with Acute Myeloid Leukemia (Alliance)