Large Transplant Center Research Articles

The Kidney Transplant: Maintaining Excellent Outcomes While Increasing Skills Acquisition

Kidney transplantation is a complex operation that incorporates multiple fundamental surgical techniques and is an excellent opportunity for surgical skill development during residency training. We hypothesized that increasing resident competency, measured as anastomosis time, could be demonstrated while maintaining high-quality surgical outcomes during the learning process. We performed a retrospective cohort study of surgical resident involvement in kidney transplantation and recorded the anastomosis time. The study population comprised adult, single organ kidney transplants (n = 2052) at a large academic transplant center between 2006 and 2019. Descriptive statistics included frequencies, medians, and means. A mixed model of anastomosis time on number of procedures was fitted. Poisson models were fitted with outcomes of the number of patients with delayed graft function and number of patients that underwent reoperation postoperatively, with the exposure being number of kidney transplants performed by resident. Results from the mixed model suggest that as the number of times a resident performs the surgery increases, the time to conduct the operation decreases with statistical significance. The Poisson regression demonstrated no significant relationship between the operative volume of a resident and postoperative complications. This study demonstrated statistical evidence that with an increase in the number of renal transplantations performed by a surgical resident, anastomosis time decreased. It also demonstrated no significant relationship between number of kidney transplants performed by a resident and postoperative complications, suggesting that patient outcomes for this operation are not adversely affected by resident involvement.

Dental evaluation and clearance prior to allogeneic hematopoietic cell transplantation.

Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. This report describes the dental status of a cohort of patients within the Chronic Graft-versus-Host Disease Consortium and treatment rendered prior to transplant. The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana-Farber: n = 241). Both centers have institutional-based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). Retrospective analysis of pre-AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care.

FTP6.3 In Hospital Delay to Laparoscopic Appendicectomy in CT Proven Appendicitis

Abstract Aims The ability to deliver emergency general surgery (EGS) is often limited by access to emergency theatres. The Royal College of Surgeons suggests that clinical audit of EGS activity will establish evidence that can contribute to service change. Laparoscopic appendicectomy is one of the most frequent EGS operations performed. The aim of this study is to quantify in hospital delay to theatre for CT proven appendicitis and examine clinical outcomes. Methods In a large major trauma and transplant centre, where emergency theatre space is shared with several specialties, data were collected on patients admitted with CT proven appendicitis over a 6-month period (01/06/2022 to 01/12/2022). Details of CT findings, intra-operative findings, as well as time of booking, operation and discharge were recorded. Results 65 patients presented with CT proven appendicitis. The average time to theatre from time of booking was 16.7 hours. 60.0% (39/65) patients took >12 hours to get to theatre. Of these, 7.7% (3/39) had perforated appendicitis on CT. 33.3% (13/39) had perforated appendicitis at the time of surgery. The average stay of patients with perforated appendicitis at the time of surgery was 4.1 days longer than those with uncomplicated appendicitis. Conclusions In hospital delay of more than 12 hours has previously been shown to be an independent risk factor for perforation. A large proportion of our patients took more than 12 hours to get to theatre and those with perforated appendicitis had an increased length of stay. Delays in delivering EGS results in increased length of stay, exacerbating the bed crisis.

When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients.

There is an ongoing need to understand whether transplantation during acute Coronavirus disease 2019 (COVID-19) can be performed safely, especially when urgent transplant is required. We collected retrospective data of all consecutive non-lung transplant recipients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) on the day of planned deceased donor organ implantation. Data were collected from two large transplant centers from 01/01/2022 to 02/01/2023. Demographics, details regarding COVID-19 infection, waitlist priority, and details regarding transplantation were obtained. A descriptive analysis was performed. A total of 12 patients were identified: 7 renal, 4 liver, and 1 heart transplant recipient. All 12 patients were vaccinated for COVID-19. Ten were asymptomatic outpatients found positive on admission and transplanted immediately. Two were in-patients with mild COVID-19 symptoms and were reactivated on the waitlist following 3 days of remdesivir when no progression to severe COVID-19 occurred. Most patients (10/12) received remdesivir posttransplant. No complications attributed to COVID-19 were noted nor were any secondary family or healthcare worker infections observed. All recipients were managed with special isolation precautions befitting their potentially infectious state. Standard induction therapy was used in all recipients. After a median follow up period of 143 days (interquartile range: 96-201 days), 3 episodes of rejection were documented, 2/7 renal recipients experienced delayed graft function, and 2/4 liver recipients required renal replacement therapy. Graft and patient survival were 100%. Transplantation can safely proceed in select, minimally symptomatic, non-lung recipients with a positive SARS-CoV-2 PCR at the time of transplant.

Next-generation sequencing-based MRD in adults with ALL undergoing hematopoietic cell transplantation.

Measurable residual disease (MRD) is an adverse prognostic factor in adult patients with acute lymphoblastic leukemia (ALL) undergoing hematopoietic cell transplant (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10-6, but the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT, patients aged ≥18 years with ALL who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014 and April 2021 and were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed before HCT (MRDpre) and up to 1 year after HCT (MRDpost). Patients were followed up for leukemia relapse and survival for up to 2 years after HCT. In total, 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10-4 (hazard ratio [HR], 3.56; 95% confidence interval [95% CI], 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR, 4.60; 95%CI, 3.01-7.02). In exploratory analyses limited to patients with B-cell ALL, the detection of post-HCT immunoglobulin H (IgH) MRD clonotypes, rather than non-IgH MRD clonotypes, was associated with relapse. In this analysis across 2 large transplant centers, we found that the detection of MRD by NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT.

Delayed referral for liver transplant evaluation worsens outcomes in chronic liver disease patients requiring inpatient transplant evaluation.

Indications to refer patients with cirrhosis for liver transplant evaluation (LTE) include hepatic decompensation or a model for end stage liver disease (MELD-Na) score ≥ 15. Few studies have evaluated how delaying referral beyond these criteria affects patient outcomes. To evaluate clinical characteristics of patients undergoing inpatient LTE and to assess the effects of delayed LTE on patient outcomes (death, transplantation). This is a single center retrospective cohort study assessing all patients undergoing inpatient LTE (n = 159) at a large quaternary care and liver transplant center between 10/23/2017-7/31/2021. Delayed referral was defined as having prior indication (decompensation, MELD-Na ≥ 15) for LTE without referral. Early referral was defined as referrals made within 3 mo of having an indication based on practice guidelines. Logistic regression and Cox Hazard Regression were used to evaluate the relationship between delayed referral and patient outcomes. Many patients who require expedited inpatient LTE had delayed referrals. Misconceptions regarding transplant candidacy were a leading cause of delayed referral. Ultimately, delayed referrals negatively affected overall patient outcome and an independent predictor of both death and not receiving a transplant. Delayed referral was associated with a 2.5 hazard risk of death. Beyond initial access to an liver transplant (LT) center, delaying LTE increases risk of death and reduces risk of LT in patients with chronic liver disease. There is substantial opportunity to increase the percentage of patients undergoing LTE when first clinically indicated. It is crucial for providers to remain informed about the latest guidelines on liver transplant candidacy and the transplant referral process.

Investigating Ineligibility of Potential Living Liver Donors for Transplantation: Experience from a Large Liver Transplant Center in Pakistan

BackgroundLiving Donor Liver Transplantation (LDLT) is common in Pakistan, where the deceased organ donation is lacking. However, not all potential living donors are suitable for the procedure due to various medical, technical, psychosocial, and ethical reasons. This study aims to investigate the reasons for the ineligibility of potential living liver donors in Pakistan. MethodsBetween June 2022 and March 2023, 530 potential living liver donors were assessed for liver transplant recipients at the Pakistan Kidney and Liver Institute & Research center (PKLI&RC). Potential donors were evaluated in three steps, including laboratory tests imaging, and consultations. Prospectively maintained data on all potential donors were examined and retrospectively assessed to identify the causes of donor rejection. ResultsOf the 530 potential living donors evaluated, 364 of the potential donors were considered ineligible (68.67% of donors were rejected). From these rejected donors, 193 (53%) were males, and 171 (47%) were females. The mean age of the rejected donors was 26 years old. The most common reason for disqualifying potential living liver donors was a withdrawal of consent (65 cases, 17.9%). Other factors contributing to ineligibility included fatty liver infiltration reflected by a liver attenuation index (LAI) < 0, future liver remnant (FLR) < 28%, and a graft-to-recipient weight ratio (GRWR) < 0.6. Medical issues, such as abnormal liver function tests and positive hepatitis serology, also resulted in disqualification. ConclusionThis study highlights the importance of meticulous assessment of potential living liver donors to ensure their safety and the success of the transplant. The high rate of withdrawal of consent and the prevalence of medical issues indicates the need for addressing ethical concerns and improving public education on the donation process. This study also emphasizes the importance of a deceased organ donation in developing countries like Pakistan to ensure the availability of organs for transplantation.

Secondary Cold Ischemia After Normothermic Machine Perfusion: A Drawback to Centralized Organ Perfusion Centers?

Secondary Cold Ischemia After Normothermic Machine Perfusion: A Drawback to Centralized Organ Perfusion Centers?

Multi-drug resistant strains as etiological agents of urinary tract infections in patients after solid organ transplantation.

Urinary tract infections (UTIs) caused by multi-drug resistant strains are a serious and growing problem in organ transplant (TX) recipients. The aim of the study was to assess the prevalence and risk factors of UTIs caused by multi-drug resistant strains in hospitalized patients after kidney or liver transplantation in a large transplant center. 392 cases of UTIs in patients after kidney or liver TX hospitalized in 2014, 2015 and 2016 were analyzed. Among the assessed cases of UTIs, 66.07% occurred in women, 33.93% - in men, 80.1% - in kidney TX recipients and 19.9% - in liver TX recipients. The median age of the patients was 57.51 years and the median time since TX was 41.44 months. Most episodes of UTIs were observed during the first year after TX - 121 (30.78%) of cases. A total of 506 pathogens were cultured: 345 Gram-negative bacteria (68.182%), 146 Gram-positive bacteria (28.854%) and 15 fungi (2.964%). More than one pathogen was found in 25.51% of urine cultures. Among bacteria (n=491), a resistance mechanism was detected in 166 (33.81%) pathogens (133 Gram-negative and 33 Gram-positive). The most common etiological agents were: E. coli ESBL- (23.72%), K. pneumoniae ESBL+ (17.19%), E. faecalis (11.27%) and E. faecium (7.71%). Diabetes was present in 129 (35.46%) of patients, and the number of UTI cases was similar in the group with and without diabetes. Compared to the general population, in hospitalized patients after kidney or liver transplantation UTIs occur more often in men and are more often caused by Gram-positive bacteria. In 33.81% of cases UTIs are caused by multi-drug resistant strains, predominantly Gram-negative bacteria.

Antibiotic stewardship implementation at the largest solid organ transplantation center in Asia: a retrospective cohort study

BackgroundUsing Antimicrobial stewardship programs (ASP) to monitor the use of antibiotics can lead to improved antibiotic use and reduced costs.MethodsThis retrospective cohort study was done at Shiraz Organ Transplant Center, the largest transplant center in Asia. Antimicrobial use, cost, clinical outcomes, and antibiotic resistance pattern were evaluated before and after ASP.ResultsThis study included 2791 patients, 1154 of whom were related to the time before ASP and 1637 to the time after ASP. During the period of the research, a total of 4051 interventions were done. The use of all classes of antibiotics was significantly reduced by ASP, with 329 DDD/100PD before the intervention compared to 201 DDD/100PD after it (p = 0.04). In addition, the overall cost of antibiotics purchased was much lower after the ASP measures were implemented ($43.10 per PD) than before implementation of the ASP measures ($60.60 per PD) (p = 0.03). After the implementation of ASP, the number of MDR isolates was significantly reduced.ConclusionThe results of our study showed that the implementation of ASP significantly reduced the number and costs of antibiotics and also the number of resistant pathogens, but did not affect the patients’ length of stay.

Low-Dose TMP-SMX for Pneumocystis jirovecii Pneumonia Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that adversely affects solid organ transplant (SOT) recipients. Published guidelines endorse 5 to 10 mg/kg/day (trimethoprim component) trimethoprim-sulfamethoxazole (TMP-SMX) as the recommended regimen for PJP prevention, often resulting in drug-related adverse effects. We investigated the use of a low-dose TMP-SMX regimen given at 2.5 mg/kg/dose once daily every Monday, Wednesday, and Friday at a large pediatric transplantation center. A retrospective chart review was conducted, including patients ages 0 to 21 years who underwent SOT from January 1, 2012, to May 1, 2020, and who were subsequently started on PJP prophylaxis with low-dose TMP-SMX for a minimum of 6 months. The primary end point was the incidence of breakthrough PJP infection on the low-dose TMP-SMX regimen. Secondary end points include the prevalence of adverse effects characteristic of TMP-SMX. A total of 234 patients were included in this study, and 6 of 234 patients (2.6%) were empirically transitioned to treatment dosing of TMP-SMX given a clinical concern for PJP, although none received a diagnosis of PJP. There were 7 patients (2.6%) who experienced hyperkalemia, 36 (13.3%) had neutropenia, and 22 (8.1%) had thrombocytopenia (all grade 4). Clinically significant serum creatinine elevations were seen in 43 of 271 patients (15.9%). Elevations of liver enzymes were seen in 16 of 271 patients (5.9%). Rash was documented in 4 of 271 patients (1.5%). In our patient cohort, low-dose TMP-SMX preserves the efficacy of PJP prophylaxis while providing an acceptable adverse effect profile.

589 - Performing a CIBMTR Data Reporting Time Study at a Large Stem Cell Transplant and Cell Therapy Center

589 - Performing a CIBMTR Data Reporting Time Study at a Large Stem Cell Transplant and Cell Therapy Center

Plasma Branched-Chain Amino Acid Concentrations and Glucose Homeostasis in Kidney Transplant Recipients and Candidates

Post-transplant diabetes mellitus (PTDM) encompasses new-onset and previously unrecognized type 2 diabetes. Kidney failure masks type 2 diabetes. Branched-chain amino acids (BCAA) are closely associated with glucose metabolism. Therefore, understanding BCAA metabolism both in kidney failure and after kidney transplantation may inform PTDM mechanisms. To understand the impact of present or absent kidney function on plasma BCAA concentrations. Cross-sectional study of kidney transplant recipients and kidney transplant candidates. Large kidney transplant center in Toronto, Canada. We measured plasma BCAA and aromatic amino acid (AAA) concentrations in 45 pre-kidney transplant candidates (15 with type 2 diabetes, 30 without type 2 diabetes) and 45 post-kidney transplant recipients (15 PTDM, 30 non-PTDM), along with insulin resistance and sensitivity by 75 g oral glucose loading for those in each group without type 2 diabetes. Plasma AA concentrations were analyzed using MassChrom AA Analysis and compared between groups. The insulin sensitivity for oral glucose tolerance tests or Matsuda index (a measure of whole-body insulin resistance), Homeostatic Model Assessment for Insulin Resistance (a measure of hepatic insulin resistance), and Insulin Secretion-Sensitivity Index-2 (ISSI-2, a measure of pancreatic β-cell response) was calculated from fasting insulin and glucose concentrations, and compared with BCAA concentrations. Each BCAA concentration was higher in post-transplant subjects than pre-transplant subjects (P < .001 for leucine, isoleucine, valine). In post-transplant subjects, each BCAA concentration was higher in PTDM versus non-PTDM (odds ratio for PTDM 3-4 per 1 SD increase in BCAA concentration, P < .001 for each). Tyrosine concentrations were also higher in post-transplant subjects than pre-transplant subjects, but tyrosine did not differ by PTDM status. By contrast, neither BCAA nor AAA concentrations were different in pre-transplant subjects with or without type 2 diabetes. Whole-body insulin resistance, hepatic insulin resistance, and pancreatic β-cell response did not differ between nondiabetic post-transplant and pre-transplant subjects. Branched-chain amino acid concentrations correlated with the Matsuda index and Homeostatic Model Assessment for Insulin Resistance (P < .05 for each) only in nondiabetic post-transplant subjects-not in nondiabetic pre-transplant subjects. Branched-chain amino acid concentrations did not correlate with ISSI-2 in either pre-transplant or post-transplant subjects. The sample size was small, and subjects were not studied prospectively for the development of type 2 diabetes. Plasma BCAA concentrations are higher post-transplant in type 2 diabetic states, but do not differ by diabetes status in the presence of kidney failure. The association of BCAA with measures of hepatic insulin resistance among nondiabetic post-transplant patients is consistent with impaired BCAA metabolism as a characteristic of kidney transplantation.

The toronto management of initially unresectable liver metastases from colorectal cancer in a living donor liver transplant program

Background: Living donor liver transplantation (LDLT) is an attractive option for patients with unresectable, bilobar, liver-only colorectal liver metastases (CRLM). However, it is not available in most centres beyond study protocols. This study describes the interim experience with LDLT for CRLM at a large transplant and hepatobiliary centre in North America.

Abstract B121: HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplant cyclophosphamide improves clinical outcomes for racial and ethnic minority patients with hematologic malignancies

Abstract Introduction: Racial and ethnic disparities exist in three areas related to hematopoietic cell transplantation (HCT): donor availability, access, and post-HCT outcomes. A significant barrier to access to HCT for patients (pts) of racial or ethnic minorities (REM) is the limited availability of fully matched donors (i.e., grafts matched at HLA-A, -B, -C, and -DRB1 loci) in volunteer registries. While mismatched unrelated donor (MMUD) grafts (i.e., &amp;lt;7/8 match) can be offered to pts without matched donors, MMUD HCT results in poor survival when traditional graft-versus-host disease (GVHD) prophylaxis (PPx) is used. GVHD PPx with post-transplantation cyclophosphamide (PTCy) is associated with favorable survival after haploidentical HCT, and promising outcomes have been reported in a prospective multicenter study utilizing PTCy in MMUD HCT. Herein, we analyzed the outcomes of an ethnically diverse cohort of pts who underwent MMUD HCT with PTCy at two large urban transplant centers. Objectives and Methods: Subjects receiving HCT from an MMUD from 2010-to 2020 at the University of Miami and Memorial Sloan-KetteringCancer Center were included. Pts were stratified by age, HCT indication, race/ethnicity, graft type, conditioning intensity, disease status, and degree of HLA mismatch. The primary study endpoint was one-year overall survival (OS). Secondary endpoints were event-free survival (EFS), non-relapse mortality (NRM), and cumulative incidence of acute and chronic GVHD. Results: A total of 82 pts were evaluated. The median age at HCT was 60 years (21-75), the most common indication for HCT was acute leukemia (51%), 41% of pts received an ablative conditioning regimen, and 50% received peripheral blood (PB) grafts. Forty-four percent identified as non-Hispanic white (NHW), and 56% identified as REM (Non-Hispanic Black: 30%; Hispanic: 64%; Asian/Pacific: 4.3%). The two groups (NHW vs. REM) were well-matched for leading HCT indication, disease-risk index, degree of mismatch, and disease status at HCT. REM pts were younger (median age at HCT 65 vs 56 years for NHW, p=0.001) and more likely to receive a PB graft (63% vs 40%, P = 0.04). One-year OS was 75%, EFS was 69%, and NRM was 16% for the entire cohort. Grade 3-4 acute GVHD at day 180 post-HCT was 15%, and one-year severe chronic GVHD was 9%. OS was comparable between 7/8-matched and highly-mismatched (&amp;lt;6/8) HCT recipients (75% vs. 76%, respectively; P &amp;gt;0.9). There were no differences in one-year OS (77% vs 74%, p = 0.9) and EFS (63% vs 72%, p = &amp;gt;0.9) between NHW and REM pts. Similarly, rates of acute (17% vs 13%, p = 0.5) and chronic GVHD (5.7% vs 11%, p = 0.5) were comparable between NHW and REM pts. Conclusion: PTCy resulted in encouraging clinical outcomes following MMUD HCT. Post-HCT OS, RFS, and GVHD rates were comparable between NHW and REM pts and those receiving 7/8 or highly mismatched grafts. Favorable post-HCT outcomes following MMUD with PTCy may increase HCT utilization and access for REM pts. Citation Format: Antonio M. Jimenez Jimenez, Sunil Iyer, Krishna Komanduri, Samantha Brown, Trent Wang, Stephanie Chinapen, Denise Pereira, Sean Devlin, Mark Goodman, Amer Beitinjaneh, Craig Sauter, Lazaros Lekakis, Miguel Angel Perales, Doris Ponce, Brian Shaffer. HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplant cyclophosphamide improves clinical outcomes for racial and ethnic minority patients with hematologic malignancies [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B121.

Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil.

Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

262. COVID-19 associated fungal co-infections in Solid Organ Transplant Recipients: A single center case series

Abstract Background During the ongoing Coronavirus disease of 2019 (COVID-19) pandemic, there have been increasing reports of viral, bacterial and fungal co-infections. Two COVID-19-associated fungal infections (CFIs) have been identified – COVID-19 associated pulmonary aspergillosis (CAPA) and COVID-19 associated mucormycosis (CAM), but incidence and occurrence in solid organ transplant recipients (SOTRs) is limited. We describe our experience with CFIs in SOTRs with COVID-19. Methods In a single center retrospective study at a large volume transplant center in South Florida, USA, we included adult SOTRs (≥18 years) diagnosed with COVID-19 between March 1st 2020 and January 31st 2022, with subsequent diagnosis of CFI. We collected information related to demographics, comorbidities, COVID-19 diagnosis and therapeutics, and CFI diagnostics and management. Data obtained was analyzed descriptively. Results We identified 612 SOTRs with COVID-19, of which 23 (3.8%) were diagnosed with CFIs. The patients were predominantly male (17/23, 73.9%), with median age of 59 years (range 43-79) [Table 1]. Twenty (86.9%) were kidney transplant recipients. Majority of SOTRs had lymphopenia (18/23, 78.3%) with elevated inflammatory markers at time of COVID-19 diagnosis. They received most commonly remdesivir and corticosteroids for COVID-19, with 22 (95.6%) needing intensive care unit admission and 19 (82.6%) needing continuous renal replacement therapy. CFIs were diagnosed at median 21 days (range, 3-161) after initial COVID-19 diagnosis. Probable CAPA was diagnosed in most patients (16/23, 69.6%), with CAM noted in 1 patient [Table 2]. 34.8% (8/23) had specific fungal species identified, with elevated fungal markers noted in 95.6% (22/23). Concurrent or prior cytomegalovirus DNAemia was noted in 26.1% (6/23). Patients were followed for median 70 days (range, 19-572), with median hospitalization duration 56 days (range, 7-204). Mortality was noted in 73.9% (17/23). Table 1:COVID-19 related clinical characteristics in study patients (N=23)Table 2:CFI-related clinical characteristics in study patients (N=23) Conclusion Fungal co-infections were noted in a small proportion of our SOTRs, with poor outcomes. Transplant physicians should have a high suspicion for early diagnosis and treatment of CFI. Further studies are needed to determine predictors for CFI and role for anti-fungal prophylaxis. Disclosures All Authors: No reported disclosures.

Ultra-Sensitive Next-Generation Sequencing Establishes the Prognostic Value of Very Low MRD in Adults with Acute Lymphoblastic Leukemia Undergoing Hematopoietic Cell Transplantation

BACKGROUND The prognostic utility of measurable residual disease (MRD) in adult acute lymphoblastic leukemia (ALL) has been defined at a sensitivity of 10-4. Measurement of MRD by ultra-sensitive next-generation sequencing (NGS) of Ig and/or TCR rearrangements has a sensitivity of 10-6 and is increasingly used across the United States to evaluate treatment response. However, the clinical utility of very low level NGS-based MRD (<10-4) is unknown. In this large multicenter cohort of adult ALL patients who underwent allogeneic hematopoietic cell transplant (HCT), we evaluated the prognostic value of ultra-sensitive NGS-based MRD. METHODS Adults (18+) with ALL who underwent HCT at Stanford University or Oregon Health and Science University (OHSU) between January 2014 and April 2021 with planned MRD monitoring using the NGS-based clonoSEQ assay (Adaptive Biotechnologies, Seattle, WA) were included. Pre-HCT MRD (MRDpre) and post-HCT MRD (MRDpost) were followed for up to one-year post-HCT. MRD was evaluated as residual clonal cells per million nucleated cells and was defined as undetectable (0), low (<10-4), high (≥10-4 to ≤10-3) and very high (>10-3). Patients were followed for leukemia relapse for up to two years. Competing-risks analyses were used to model the hazard of relapse according to MRDpre and MRDpost levels. A univariate analysis using a Fine-Gray subdistribution hazard competing risk regression model was used to estimate the effect of MRDpre level on the cumulative incidence of relapse. A Cox regression model with time-varying covariates was fit to evaluate the association between MRDpre and MRDpost levels with relapse. RESULTS 158 ALL patients who underwent HCT (Stanford n = 116, OHSU n = 42) had a trackable clonoSEQ clone. The median age was 43 years (range 18-77); 136 patients (86%) had B-ALL, 22 (14%) had T-ALL, and 131 (83%) underwent myeloablative HCT. Of the 122 patients with MRDpre assessment, MRDpre was undetectable, low, high, and very high in 82 (67%), 24 (20%), 11 (9%), and 5 (4%), respectively. Of the 111 patients with both MRDpre and at least one MRDpost assessments, 38 had at least one positive MRDpost result. The cumulative incidence of relapse differed significantly according to level of MRDpre (Figure 1), including among patients with low MRDpre of <10-4 where post-HCT relapse risk was strikingly higher than in patients with undetectable MRDpre (HR 3.56, 95% CI 1.39-9.15, p = 0.01). A very strong association with post-HCT relapse was also seen in patients with detectable MRDpost at any level (including <10-4), even after controlling for MRDpre (HR 4.41, 95% CI 2.90-6.70, p < 0.0001). Finally, we found that patients entering HCT with undetectable MRDpre who remained undetectable through the first year of MRDpost monitoring had <10% likelihood of relapse in the second post-HCT year (Figure 2). In contrast, patients entering HCT with detectable MRDpre had an ongoing risk of continued detectable of MRDpost without a clear plateau of relapse risk post-HCT. CONCLUSION In this analysis across two large transplant centers, we found that detection of MRD by ultra-sensitive NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT. Detectable MRDpre even at a low level of <10-4 increases the risk of post-HCT relapse. The presence of MRDpost at any level following HCT also substantially increases the risk of relapse. Finally, we found that patients with undetectable MRDpre who continue to have undetectable MRDpost through the first year of monitoring have excellent post-HCT outcomes. *ECL, SD, and JS contributed to this work equally Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

End of Treatment Positron Emission Tomography Response and Outcomes in Post-Transplant Lymphoproliferative Disorder

Introduction: Although end of treatment (EOT) response assessment using Fluorine-18-fluorodeoxyglucose positron emission tomography (PET) has proven highly predictive of disease remission in Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma, there is little data on the prognostic significance of PET response in patients with post-transplant lymphoproliferative disorder (PTLD). Optimal treatment of patients with PTLD is complex and better understanding of the significance of EOT imaging could help guide subsequent therapeutic decisions. Methods: As part of a multi-institutional study of viral genomes in PTLD, we collected clinical data (demographics, transplant and PTLD characteristics, treatment, imaging, and patient survival) from three large organ transplant centers in the United States from 1991 onwards. Patients who were PET negative at EOT considered to have a complete remission (CR), patients with decrease in FDG avidity who were still PET positive considered to have a partial remission (PR), and patients with stable or increasing FDG avidity considered to have no remission or progressive disease (NR/PD). Time-to-event outcomes (time to death and time to death or relapse) were analyzed using the Kaplan Meier method. Results: Among 147 pediatric and adult patients with PTLD, imaging at diagnosis and EOT included PET n=94 (64%), computed tomography (CT) n=77 (53%), and/or magnetic resonance imaging (MRI) n=14 (10%). Median recipient age at first transplant was 29.6 years (IQR 14.8 to 25.9), and 57.5% were male. Transplants included kidney (29%), heart (27%), liver (18%), lung (18%), hematopoietic (7%), intestine (6%), or pancreas (3%). Sites of PTLD were lymph node (57%), gastrointestinal tract (34%), lung (19%), disseminated (10%), liver (8%), central nervous system (4%), kidney (3%), bone marrow (3%), or other (41%). PTLD subtypes included monomorphic diffuse large B-cell lymphoma (DLBCL) (69%), polymorphic (17%), classical HL (8%), or non-destructive (5%). All non-destructive and polymorphic PLTD was Epstein-Barr virus (EBV) positive while 60.6% of DLBCL and 75% of classical HL were EBV positive. Treatments varied but included reduction of immunosuppression in 65.6% and rituximab or chemotherapy in 62.4% of patients. For 84 patients with PET scans and outcome data, patients who achieved CR (59/84; 70.2%) experienced a subsequent progression-free median survival of 13.5 years compared with 8.8 years for patients with PR (11/84; 13.1%) and 1.4 years for patients with NR/PD (14/84; 16.7%) (p<0.0001, Figure A). Median overall survival was 14.7 years for patients with CR (60/85; 70.6%), not reached for patients with PR (11/85; 12.9%), and 1.4 years for patients with NR/PD (14/85; 16.5%) (p=0.0026, Figure B). 20.8% of patients who achieved CR subsequently relapsed compared to 42.9% of patients with PR. 81.8% of patients with NR/PD experienced relapse or death. Conclusion: End of therapy PET identifies a subgroup of patients with CR who are at low risk for relapse. While patients with NR/PD had poor prognosis, patients with PR represent an intermediate group who are PET positive at the EOT but can achieve long-term remission without additional therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

No Evidence of Racial Survival Disparity Gap Among Blacks Vs Whites with Multiple Myeloma Post Autologous Stem Cell Transplant: A Study from over a Decade

Introduction: Multiple myeloma is a plasma cell neoplasm that predominately impacts black patients. It is well documented that racial disparities exist among blacks vs whites. This disparity adversely impacts survival and rates of autologous stem cell transplant among black patients, hypothesized to be due to unequal access to care. We seek to evaluate racial survival disparities among patients with multiple myeloma who underwent autologous stem cell transplant from 2011-2021 at one of the largest bone marrow transplant centers in Louisiana. Methods: Retrospective study from a large bone marrow transplant center in Louisiana. De-identified patient records assessed for patient demographics, including self-reported race, age, sex, and diagnosis characteristics including diagnosis of multiple myeloma, PET staging, R-ISS staging, date of transplant and death. Data was analyzed using Chi-Squared analysis. Statistical significance was measured as p<0.05. Results Of 238 patients with multiple myeloma who underwent autologous stem cell transplants from 2011-2021, 101 patients were female, and 137 patients were male. 107 patients were self-identified as black, 124 self-identified as white, 7 patients as other. Both racial groups (black and white) had equal number of patients in R-ISS stage I-III. Analysis of one-year survival post-autologous stem cell transplant among black vs white patients was not statistically significant. There was no trend of increased mortality among either racial groups. There was no evidence of increased progression among racial groups. There was also no correlation between sex and survival. Conclusion Louisiana encompasses a greater proportion of black population (33%) as compared to the national average (13%). Using retrospective data from one of the largest bone marrow transplant centers and referral centers, there was no evidence of a one year survival disparity among race and progression free survival among patients with multiple myeloma who received autologous stem cell transplant from 2011-2021. This may be due to equal access to care, referral-based process, and navigation assistance.