Browsing by Subject "Transplant"
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Item A Cost-Effectiveness Analysis: Personal Systems Approach in Improving Medication Adherence in Adult Kidney Transplant Patients(Wolters Kluwer, 2022) Whittington, Melanie; Goggin, Kathy; Glasscock, Ernest L.; Noel-MacDonnell, Janelle; Hathaway, Donna; Remy, Laura; Aholt, Dana; Clark, Debra; Miller, Courtney; Ashbaugh, Catherine; Wakefield, Mark; Bartlett Ellis, Rebecca; Russell, Cynthia; School of NursingInterventions to improve medication non-adherence in transplantation have recently moved from a focus on motivation and intention, to a focus on person-level quality improvement strategies. These strategies link adherence to established daily routines, environmental cues and supportive people. The objective of this evaluation was to estimate the cost of implementation and the cost-effectiveness of a person-level intervention shown to increase medication adherence. To estimate the intervention costs, a direct measure micro-costing approach was used following key informant interviews with project champions and a review of implementation expenditures. Cost-effectiveness was calculated by comparing the incremental implementation costs and healthcare costs associated with non-adherence to the incremental percent adherent, defined as the percent of patients who took greater or equal to 85% of their medication doses, for each pairwise comparison. The intervention was low-resource to implement, costing approximately $520 to implement per patient, and was associated with significant improvements in medication adherence. These implementation costs were more than outweighed by the expected healthcare savings associated with improvements in adherence. This person-level intervention is a low cost, efficacious intervention associated with significant statistical and clinical improvements in medication adherence in adult kidney transplant recipients.Item Age no Bar – a CIBMTR analysis of Elderly Patients undergoing Autologous Hematopoietic Cell Transplantation for Multiple Myeloma(Wiley, 2020) Munshi, Pashna N.; Vesole, David; Jurczyszyn, Artur; Zaucha, Jan Maciej; St. Martin, Andrew; Davila, Omar; Agrawal, Vaibhav; Badawy, Sherif M.; Battiwalla, Minoo; Chhabra, Saurabh; Copelan, Edward; Kharfan-Dabaja, Mohamed A.; Farhadfar, Nosha; Ganguly, Siddhartha; Hashmi, Shahrukh; Krem, Maxwell M.; Lazarus, Hillard M.; Malek, Ehsan; Meehan, Kenneth; Murthy, Hemant S.; Nishihori, Taiga; Olin, Rebecca L.; Olsson, Richard F.; Schriber, Jeffrey; Seo, Sachiko; Shah, Gunjan; Solh, Melhem; Tay, Jason; Kumar, Shaji; Qazilbash, Muzaffar H.; Shah, Nina; Hari, Parameswaran N.; D'Souza, Anita; Medicine, School of MedicineBackground: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2 . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2 , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P = .01]), likely representing frailty. Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.Item Cell-Free DNA and Active Rejection in Kidney Allografts(American Society of Nephrology, 2017-07) Bloom, Roy D.; Bromberg, Jonathan S.; Poggio, Emilio D.; Bunnapradist, Suphamai; Langone, Anthony J.; Sood, Puneet; Matas, Arthur J.; Mehta, Shikha; Mannon, Roslyn B.; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C.; Cohen, David; Weir, Matthew R.; Hiller, David; Prasad, Preethi; Woodward, Robert N.; Grskovic, Marica; Sninsky, John J.; Yee, James P.; Brennan, Daniel C.; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators; Medicine, School of MedicineHistologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.Item Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing(Wiley, 2015-07) Birdwell, Kelly A.; Decker, Brian; Barbarino, Julia M.; Peterson, Josh F.; Stein, C. Michael; Sadee, Wolfgang; Wang, Danxin; Vinks, Alexander A.; He, Yijing; Swen, Jesse J.; Leeder, J. Steven; van Schaik, RHN; Thummel, Kenneth E.; Klein, Teri E.; Caudle, Kelly E.; MacPhee, Iain A.M.; Department of Medicine, IU School of MedicineTacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).Item Comparison of hepatic MDCT, MRI, and DSA to explant pathology for the detection and treatment planning of hepatocellular carcinoma(The Korean Association for the Study of the Liver, 2016-12) Ladd, Lauren M.; Tirkes, Temel; Tann, Mark; Agarwal, David M.; Johnson, Matthew S.; Tahir, Bilal; Sandrasegaran, Kumaresan; Department of Radiology and Imaging Sciences, IU School of MedicineBACKGROUND/AIMS: The diagnosis and treatment plan for hepatocellular carcinoma (HCC) can be made from radiologic imaging. However, lesion detection may vary depending on the imaging modality. This study aims to evaluate the sensitivities of hepatic multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) in the detection of HCC and the consequent management impact on potential liver transplant patients. METHODS: One hundred and sixteen HCC lesions were analyzed in 41 patients who received an orthotopic liver transplant (OLT). All of the patients underwent pretransplantation hepatic DSA, MDCT, and/or MRI. The imaging results were independently reviewed retrospectively in a blinded fashion by two interventional and two abdominal radiologists. The liver explant pathology was used as the gold standard for assessing each imaging modality. RESULTS: The sensitivity for overall HCC detection was higher for cross-sectional imaging using MRI (51.5%, 95% confidence interval [CI]=36.2-58.4%) and MDCT (49.8%, 95% CI=43.7-55.9%) than for DSA (41.7%, 95% CI=36.2-47.3%) (P=0.05). The difference in false-positive rate was not statistically significant between MRI (22%), MDCT (29%), and DSA (29%) (P=0.67). The sensitivity was significantly higher for detecting right lobe lesions than left lobe lesions for all modalities (MRI: 56.1% vs. 43.1%, MDCT: 55.0% vs. 42.0%, and DSA: 46.9% vs. 33.9%; all P<0.01). The sensitivities of the three imaging modalities were also higher for lesions ≥2 cm vs. <2 cm (MRI: 73.4% vs. 32.7%, MDCT: 66.9% vs. 33.8%, and DSA: 62.2% vs. 24.1%; all P<0.01). The interobserver correlation was rated as very good to excellent. CONCLUSION: The sensitivity for detecting HCC is higher for MRI and MDCT than for DSA, and so cross-sectional imaging modalities should be used to evaluate OLT candidacy.Item Histoplasmosis in Solid Organ Transplantation(MDPI, 2024-02-02) Barros, Nicolas; Wheat, L. Joseph; Medicine, School of MedicineHistoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global distribution with shifting epidemiology during recent decades. While in immunocompetent individuals infection is usually self-resolving, solid organ transplant recipients are at increased risk of symptomatic disease with dissemination to extrapulmonary tissue. Diagnosis of histoplasmosis relies on direct observation of the pathogen (histopathology, cytopathology, and culture) or detection of antigens, antibodies, or nucleic acids. All transplant recipients with histoplasmosis warrant therapy, though the agent of choice and duration of therapy depends on the severity of disease. In the present article, we describe the pathogenesis, epidemiology, clinical manifestations and management of histoplasmosis in solid organ transplant recipients.Item How old is too old? In vivo engraftment of human peripheral blood stem cells cryopreserved for up to 18 years - implications for clinical transplantation and stability programs(Baishideng, 2020-05-16) Underwood, John; Rahim, Mahvish; West, Carijo; Britton, Rebecca; Skipworth, Elaine; Graves, Vicki; Sexton, Steven; Harris, Hillary; Schwering, Dave; Sinn, Anthony; Pollok, Karen E.; Robertson, Kent A.; Goebel, W. Scott; Hege, Kerry M.; Pediatrics, School of MedicineBACKGROUND Peripheral blood stem cells (PBSC) are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant. Long term cryopreservation is commonly defined as five years or longer, and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft. Clinical programs, stem cell banks, and regulatory and accrediting agencies interested in product stability would benefit from such data. Thus, we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2Rγnull (NSG) mice. AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units. METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health. These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice, and the pre-freeze and post-thaw characteristics of the units were compared. Progenitor function was assessed using standard colony-forming assays. CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function. RESULTS Ten PBSC units with mean of 17 years in cryopreservation (range 13.6-18.3 years) demonstrated a mean total cell recovery of 88% ± 12% (range 68%-110%) and post-thaw viability of 69% ± 17% (range 34%-86%). BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw. Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units. All mice demonstrated long-term engraftment at 12 wk with mean 34% ± 24% human CD45+ cells, and differentiation with presence of human CD19+, CD3+ and CD33+ cells. Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies. CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice, signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.Item Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program(Wiley, 2023) Tillman, Emma; Nikirk, Miley G.; Chen, Jeanne; Skaar, Todd C.; Shugg, Tyler; Maddatu, Judith P.; Sharfuddin, Asif A.; Eadon, Michael T.; Medicine, School of MedicineTacrolimus is a calcineurin inhibitor with a narrow therapeutic range and is metabolized by cytochrome P450 (CYP) isoenzymes CYP3A4 and CYP3A5. The Clinical Pharmacogenetic Implementation Consortium published evidence-based guidelines for CYP3A5 normal/intermediate metabolizers prescribed tacrolimus, yet few transplant centers have implemented routine testing. The objective of this study was to implement preemptive CYP3A genotyping into clinical practice in a large kidney transplant program and to evaluate workflow feasibility, potential clinical benefit, and reimbursement to identify barriers and determine sustainability. Preemptive pharmacogenetic testing for CYP3A5 and CYP3A4 was implemented in all patients listed for a kidney transplant as part of standard clinical care. Genotyping was performed at the listing appointment, results were reported as discrete data in the electronic medical record, and education and clinical decision support alerts were developed to provide pharmacogenetic-recommended tacrolimus dosing. During this initial phase, all patients were administered standard tacrolimus dosing, and clinical and reimbursement outcomes were collected. Greater than 99.5% of genotyping claims were reimbursed by third-party payers. CYP3A5 normal/intermediate metabolizers had significantly fewer tacrolimus trough concentrations within the target range and a significantly longer time to their first therapeutic trough compared to poor metabolizers. The challenge of tacrolimus dosing is magnified in the African American population. The US Food and Drug Administration drug label recommends increased starting doses in African ancestry, yet only ≈66% of African Americans in our cohort were normal/intermediate metabolizers who required higher doses. Routine CYP3A5 genotyping may overcome this issue by using genotype over race as a more accurate predictor of drug response.Item Post Liver Transplant Patient Outcomes and Survival: Impact of Demographics and Psychosocial Factors(2022-08) French, Marcia Mount; Kim, Hea-Won; Adamek, Margaret E.; Glassburn, Susan; Mangus, Richard S.Many persons with cirrhosis and eventually end stage liver disease (ESLD) are unable to meet the eligibility criteria for becoming a candidate for a liver transplant (LT). Currently, approximately 17,000 persons in the United States (U.S.) need a LT to survive, though only about 8,000 LT’s are performed each year; a LT is the only option for survival. The genesis of ESLD is most typically attributed to alcohol abuse, chronic hepatitis B or C, non-alcoholic fatty liver disease, autoimmune hepatitis, biliary atresia (new-born liver disease), or metabolic disorders. The etiology of adult LT recipients in 2017 for the U.S. were non-alcoholic fatty liver disease (31%) and alcoholic liver disease (25.1%). This study is guided by the Critical Social and Stress Coping Theories to assist in exploring potential health disparities prevalent in LT recipients. The aim of this study is to explore the psychological and demographic characteristics of 1297 LT recipients between 2010-2020 in an Indiana transplant center and identify potential disparities impacting 10-year survival rates. This exploratory, cross-sectional secondary analysis found that race/ethnicity, histories of mental illness, substance use/abuse, social support networks, education, marital status, and insurance sources held no statistical significance for 10-year survival rates. To date the screening process for each of those demographics appears to be effective and efficient. A Cox regression analysis revealed having a history of criminality significantly impacts 10-year survival rates. To address these findings the consideration for increased support and follow-up for patients with a history of criminality may positively impact 10-year survival rates.Item Primary Graft Dysfunction Grade 3 following Pediatric Lung Transplantation is Associated with Chronic Lung Allograft Dysfunction(Elsevier, 2023) Wong, Wai; Johnson, Brandy; Cheng, Pi Chun; Josephson, Maureen B.; Maeda, Katsuhide; Berg, Robert A.; Kawut, Steven M.; Harhay, Michael O.; Goldfarb, Samuel B.; Yehya, Nadir; Himebauch, Adam S.; Pediatrics, School of MedicineBackground: Severe primary graft dysfunction (PGD) is associated with the development of bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), in adults. However, PGD associations with long-term outcomes following pediatric lung transplantation are unknown. We hypothesized that PGD grade 3 (PGD 3) at 48- or 72-hours would be associated with shorter CLAD-free survival following pediatric lung transplantation. Methods: This was a single center retrospective cohort study of patients ≤ 21 years of age who underwent bilateral lung transplantation between 2005 and 2019 with ≥ 1 year of follow-up. PGD and CLAD were defined by published criteria. We evaluated the association of PGD 3 at 48- or 72-hours with CLAD-free survival by using time-to-event analyses. Results: Fifty-one patients were included (median age 12.7 years; 51% female). The most common transplant indications were cystic fibrosis (29%) and pulmonary hypertension (20%). Seventeen patients (33%) had PGD 3 at either 48- or 72-hours. In unadjusted analysis, PGD 3 was associated with an increased risk of CLAD or mortality (HR 2.10, 95% CI 1.01-4.37, p=0.047). This association remained when adjusting individually for multiple potential confounders. There was evidence of effect modification by sex (interaction p = 0.055) with the association of PGD 3 and shorter CLAD-free survival driven predominantly by males (HR 4.73, 95% CI 1.44-15.6) rather than females (HR 1.23, 95% CI 0.47-3.20). Conclusions: PGD 3 at 48- or 72-hours following pediatric lung transplantation was associated with shorter CLAD-free survival. Sex may be a modifier of this association.