Real-world evidence (RWE) has been used to improve quality of care, accelerate innovation, and evaluate emerging therapies for drugs, devices, and biologics. The Coordinated Registry Network (CRN), aggregating and linking highly curated patient data, has emerged as a model for RWE generation that has guided the development of the ASH Research Collaborative® (ASH RC) Data Hub. With the aim of bolstering research, enhancing clinical care, and expediting evidence generation using RWE, ASH RC, and the Innovative Genomics Institute (IGI) launched a joint initiative, "Accelerating Innovations for Sickle Cell Disease (SCD) with Real-World Evidence," to evaluate and make recommendations to the Data Hub. An expert panel used a "maturity model" to evaluate: 1) Data Hub standardization of RWE guidelines to ensure successful monitoring of new therapies' safety and effectiveness; and 2) the Data Hub's engagement with patients (including collection of data on patient experience) and collaboration among partners, including regulators, industry, and clinicians. The Data Hub gathers patient-level data from electronic health records, with plans to incorporate data from individuals receiving gene therapy. The program is currently curating and aggregating data on approximately 27,000 individuals with SCD cared for across 22 hospitals in the United States. The SCD Data Hub Program includes a total of 56 centers, some of which are not yet contributing data, which will increase the total cohort to approximately 50,000 patients. The unique organizational structure of the CRN model facilitates acceleration of innovation through collaborative relationships between multiple clinical sites and partners with various evidentiary needs.

OBJECTIVES: Individuals younger than 65 years can qualify for Medicare if they have long-term disabilities or certain qualifying conditions. These beneficiaries-particularly the non-dual-eligible population-may experience cost and access barriers to medical care. We examined the association between Medicare coverage type and reported barriers to care. STUDY DESIGN: Multivariable linear probability models assessed the association between self-reported Medicare coverage and patient-reported outcomes by dual-eligibility status. METHODS: Using 2012-2020 data from the Health and Retirement Study, we compared self-reported sociodemographic and health-related characteristics of non-dual-eligible and dual-eligible beneficiaries aged 50 to 64 years by Medicare coverage type at their baseline interview. We then examined the following self-reported outcomes: experiencing cost-related medication nonadherence, delaying care due to cost, not having a usual source of care, and having trouble finding a doctor. RESULTS: Among non-dual-eligible beneficiaries, enrollment in traditional Medicare (TM) plus supplemental coverage vs TM with no supplemental coverage was associated with lower reported rates of experiencing cost-related medication nonadherence (-7.5 percentage point [PP] change; 95% CI, -12.1 to-3.0), delaying care due to cost (-9.8 PP; 95% CI, -13.3 to-6.3), and having no usual source of care (-5.5 PP; 95% CI, -8.9 to-2.1). Compared with TM with no supplement, Medicare Advantage enrollment was associated with lower rates of delaying care due to cost (-4.2 PP; 95% CI, -7.6 to-0.7) and having no usual source of care (-5.2 PP; 95% CI, -8.2 to-2.3). Among dual-eligible beneficiaries, outcomes largely did not differ by coverage type. Switching from traditional Medicare to Medicare Advantage was associated with trouble finding a doctor for dual-eligible beneficiaries. CONCLUSIONS: Enrollment in less generous Medicare coverage was associated with greater cost and access barriers to care for beneficiaries younger than 65 years.

Understanding the downstream consequences of initial Medicare plan selection is necessary to ensure access to and affordability of health care services, especially for older adults with serious illness. We used 2008-2020 data from the Health and Retirement Study to estimate financial and health burden by initial Medicare plan selection (traditional Medicare without supplemental coverage, traditional Medicare plus supplemental coverage, or Medicare Advantage) and self-reported history of cancer. Initially choosing benefits with greater financial protections (either traditional Medicare plus supplemental coverage or Medicare Advantage) relative to traditional Medicare without supplemental coverage was associated with lower levels of out-of-pocket spending and a lower likelihood of reporting cost-related medication nonadherence and fair or poor health. Policymakers should consider improving the adequacy of traditional Medicare coverage to ensure the affordability of health care services and reduce the burden of serious illness among older adults, especially those with a history of cancer.

Background The increasing use of targeted oral anticancer agents (OAAs) has transformed cancer treatment, yet patient adherence in real-world settings remains suboptimal. This protocol outlines a multi-phasic, hybrid effectiveness-implementation trial designed to develop, implement, and evaluate a risk-adapted, longitudinal medication adherence intervention for patients prescribed OAAs. Methods Drawing on social cognitive theory, intervention mapping, and implementation science, the study aims to address barriers at cognitive, behavioral, and environmental levels that impact adherence. Phase 1 identifies implementation barriers and refines strategies, informed by expert input and semi-structured interviews. Phase 2 incorporates patient-centered feedback to tailor a theory-driven intervention targeting adherence barriers. In Phase 3, the intervention is piloted across diverse clinical settings to assess its effectiveness and implementation feasibility. Conclusion This trial aims to deliver a scalable and sustainable model for adherence support, with broad implications for improving patient outcomes and integrating adherence monitoring in routine cancer care.

Accurate assessment of performance status (PS) in oncology care is crucial for improving clinical decisions, therapy selection and anticipated risks of treatment toxicity. While physical function is traditionally assessed in the clinic, in-clinic instruments do not capture the full spectrum of daily functioning. Digital health technologies (DHTs) can address this limitation by passively monitoring patients in their daily environment. Our study showed at-home physical activity and gait metrics from DHTs were associated with self-reported PS in participants with cancer, and these metrics had greater discriminatory power than in-clinic measures among this cohort. The DHT-derived metrics were also significantly correlated with patient-reported-outcomes, and used of the devices was broadly acceptable to study participants. Therefore, integrating DHTs into oncological practice could significantly refine how PS is measured and utilized, ultimately enhancing treatment decision-making and clinical outcomes. (ClinicalTrials.gov NCT03952767).

Background:In this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research). Methods:Adult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total-body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included. Results:The acute myeloid leukemia (AML) cohort (N = 480, 38.8%) indicated that overall survival (OS) was poorer in CY/TBI+AraC (hazard ratio [HR] 1.46, p < 0.001) and CY/TBI+VP16 (HR 1.39, p = 0.059) compared to CY/TBI. Relapse was not suppressed, while treatment-related mortality (TRM) was significantly higher (HR 1.78 and 1.74, p < 0.001 and 0.018, respectively). In the acute lymphoblastic leukemia (ALL) cohort (N = 3901, 61.2%), OS was comparable among these regimens. With intensified regimens, relapse was significantly suppressed in CY/TBI+VP16 (HR 0.74, p = 0.005), while TRM was higher (HR 1.21, p = 0.077). No interactions were observed regarding the country. Conclusion:In AML adding AraC and VP16 to CY/TBI had an adverse effect on OS. Conversely, in ALL, adding VP16 or AraC to CY/TBI did not affect survival, but the addition of VP16 reduced the risk of relapse. Clinical Trial Registration:The authors have confirmed clinical trial registration is not needed for this submission.

Clinical trials inform cancer care, yet real-world outcomes often diverge due to patient-related factors, like age, organ dysfunction, and nonadherence to oral anticancer agents (OAAs). While oncology organizations emphasize patient support programs, practical guidance on designing and implementing these programs is limited. We conducted a two-phase, mixed-methods study to enhance the adoption, implementation, and sustainability of an OAA adherence program (OAP). In phase 1, we used implementation mapping (IM) with a multidisciplinary expert panel to develop six strategies: (1) memorandum of understanding (MOU), (2) data-driven presentation, (3) standard operating procedures (SOPs), (4) motivational interviewing (MI) training, (5) electronic health record (EHR) templates, and (6) key performance indicators (KPIs). In phase 2, oncology professionals (n = 34) completed surveys, and a subset (n = 10) participated in interviews to assess feasibility, acceptability, and appropriateness. EHR templates and SOPs were rated as the most feasible and acceptable strategies, while MI training and formal agreements received moderate ratings. Interviews highlighted the importance of leadership buy-in, incremental implementation, and clear documentation. Participants valued KPIs for tracking adherence and outcomes but noted resource constraints and staff workload as challenges. Using IM, we co-developed strategies to activate OAA adherence-focused clinical programs. Tools standardizing care, like EHR templates and SOPs, were highly endorsed. Future work will test these strategies in a hybrid trial to improve real-world oncology outcomes.

Background The impact of hospital-acquired venous thromboembolism (VTE) on short-term mortality is not well characterized. Objectives We sought to examine the association of hospital-acquired VTE with 10-day in-hospital mortality. Methods We conducted a retrospective cohort study using electronic health records from 6 US hospital systems. We included medical service admissions between 2016 and 2022 and excluded admissions of patients with VTE present at admission. We matched each admission with hospital-acquired VTE with ≤4 admissions without hospital-acquired VTE. The primary outcome was in-hospital mortality within 10 days of the VTE event or the corresponding hospital date for admissions without VTE. We used adjusted conditional logistic regression to estimate the associations of hospital-acquired VTE, overall and by VTE subtype, with in-hospital mortality. Results Among 1827 admissions with hospital-acquired VTE, 5.3% died, and among 7091 matched admissions without hospital-acquired VTE, 3.3% died. Compared with admissions without hospital-acquired VTE, admissions with hospital-acquired VTE had 69% higher odds of 10-day in-hospital mortality (adjusted odds ratio, 1.69; 95% CI, 1.29, 2.21). The adjusted odds ratios for 10-day mortality by hospital-acquired VTE subtype were 3.20 (95% CI, 1.85, 5.53) for pulmonary embolism, 1.88 (95% CI, 1.25, 2.81) for lower extremity deep vein thrombosis (DVT), and 0.81 (95% CI, 0.45, 1.46) for upper extremity DVT. Conclusion Compared with admissions without hospital-acquired VTE, admissions with hospital-acquired pulmonary embolism and hospital-acquired lower extremity DVT were associated with 3- and 2-fold increased odds of 10-day mortality, respectively.

PURPOSE:Public reporting of health care outcomes can have unintended effects such as inappropriate risk aversion in patient selection. METHODS:The center-specific survival analysis annually assigns all hematopoietic cell transplantation (HCT) centers in the United States a +1, -1, or 0 score for observed outcomes that are above, below, or within a center-specific predicted range of outcome. For each index year (2012-2016), centers receiving a -1 score after 0 scores in the preceding 2 years were compared with contemporaneous centers with as-predicted outcomes (0 score). Changes in the patient population characteristics in the 3 years before versus the 3 years after the index years were compared between the newly below-expected centers (NBCs) and the controls. A multivariate model adjusted for baseline patient population characteristics and center volume. RESULTS:No differences in patient selection behavior were identified when comparing the NBCs with the controls across eight key patient population characteristics. For the statistically modeled (predicted) 1-year overall survival (OS), reflecting a holistic measure of centers' patient population risk, we observed no statistically significant difference in change (-0.23% [95% CI, -1.4 to 0.9]; P = .70). The observed OS increased in both NBCs and controls by 0.9% and 4.5%, respectively, without statistically significant difference in change. CONCLUSION:Centers receiving a -1 score were not observed to deviate significantly from patient selection trends in the HCT field. These findings suggest that public reporting of HCT outcomes in the United States does not result in unintended bias against HCT for high-risk patients.

The past few decades have witnessed significant advancements in stem cell transplantation and cell therapy (TCT). This has allowed their expanded use in older patients and those with comorbidities with favorable outcomes. However, these procedures carry significant risks, such as graft-versus-host disease, infection, cytokine release syndrome, and immune effector cell-associated neurotoxicity. Therefore, physical function assessment is crucial to assess patient fitness and potential optimization before and after TCT. The existence of diverse assessment tools makes implementation, comparison, and sharing knowledge among centers difficult. This paper proposes a tiered approach aiming to harmonize physical assessment in the TCT. This allows healthcare facilities to prioritize recommended assessments based on their current capabilities and resources. TCT patients should receive comprehensive physical assessments pre- and post-TCT using a combination of both patient-reported and objective measures. For patient-reported measures, the Patient-Reported Outcomes Measurement Information System should be considered. For objective measures, we recommend considering a physical performance assessment (eg, gait speed) or muscle strength assessment (eg, hand grip), if feasible. Albumin and C reactive protein are also informative in predicting the risk of nonrelapse mortality. Other composite tools, questionnaire libraries, biomarkers, imaging, and wearables can be added according to research and clinical needs. A care workflow needs to be in place in case any impairment is found during the evaluation with goals of increasing physiologic reserve and mitigating stressors. This tiered approach will increase awareness and adoption of these tools and hence improve patient care, facilitate data sharing, and enhance collaboration in this field.

Patient-reported outcomes (PROs) to measure quality of life (QOL) and other symptoms play an increasingly important role in clinical trials and regulatory approvals for hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. However, their adoption has been hindered by wide heterogeneity in the choice of PRO measures for clinical research, including the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT) and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) inventories. In addition, the potential for PRO integration into routine standard-of-care (SOC) practice for patients undergoing HCT or CAR-T therapy has not yet been realized. As part of a coordinated effort by 3 American Society for Transplantation and Cellular Therapy Special Interest Groups, we developed best practices for PRO integration in adult and pediatric recipients of HCT and CAR-T therapy. We strongly encourage the use of the Patient-Reported Outcomes Measurement Information System (PROMIS) or the PRO version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) instruments as the primary PRO measures for most HCT and CAR-T trials. Measures such as the PROMIS-29 inventory can be used for QOL assessments, while PRO-CTCAE item banks can be used for specific symptoms. Rationales for our strong recommendation to move from FACT-BMT and EORTC QLQ-C30 to PROMIS/PRO-CTCAE instruments include: (1) free licensing and ease of implementation, including in electronic medical records; (2) psychometric validation in a variety of oncologic settings, including during inpatient hospitalizations; (3) translation into multiple languages, with validation in both adult and pediatric settings; and (4) adoption into centrally collected PRO protocols from the Center for International Blood and Marrow Transplant Research for both HCT and CAR-T recipients. Steps to operationalize these PRO measures are discussed, as are methods to migrate existing data from legacy PRO instruments. We similarly recommend the consideration of PRO integration into SOC clinical practice, including the development of threshold-based workflows to both personalize and standardize care in this setting. Other panel recommendations include the use of standardized timepoints for longitudinal PRO assessments and the inclusion of patient advocates when implementing PRO measures. Implementing these steps will improve the ability of PROs to improve outcomes for patients undergoing HCT or CAR-T therapy, both in trials and-more importantly-in SOC practice.

PURPOSE Empirical evidence underscores both benefits of telehealth visits and persistent disparities in use for Black adults. Guided by the Technology Acceptance Model, we evaluated perceptions regarding telehealth visits among Black and Non-Black adults receiving cancer care from two academic health systems. METHODS Between April 2022 and October 2023, a survey was conducted among adult patients treated for cancer in the past 3 years. Survey recruitment was stratified by visit type (telehealth or in-person) and race. Before a scheduled oncology visit, respondents completed a telephone survey to assess their perceptions of usefulness, ease of use, and attitudes toward telehealth visits. Frequency differences were estimated using chi-square tests, and prevalence differences using logistic regression. RESULTS The survey was completed by 773 respondents (42% Black) with a 15% response rate. Black respondents were younger and less likely to report male sex, being married, having a college education, comfortable income, or confidence in medical and e-literacy. Compared with Non-Black respondents, Black respondents perceived telehealth visits as less useful for determining health needs (37% v 48%) and asking questions (9% v 15%). They thought that telehealth visits were less easy with regard to understanding their health care provider (14% v 21%) and the ability to connect (23% v 30%). Black respondents expressed more concern about internet access (26% v 15%), access to electronic devices (17% v 9%), and finding assistance for connecting (24% v 12%). They also found telehealth visits to be less private (19% v 34%). CONCLUSION Racial differences in telehealth ease of use and usefulness perceptions highlight the need for oncology practices to couple connectivity support with effective communication strategies to avoid disparities in oncology telehealth services.

Lower birth rates and higher pregnancy loss are observed after childhood cancer. Studies specific to adolescent and young adult (AYA) cancer rarely have information on pregnancies that do not end in live birth, fertility preservation strategies, or detailed cancer treatment information to assess these risks. To address this gap, we examined pregnancy outcomes after cancer in a cohort of 30,020 AYAs with detailed clinical records. We identified 6021 survivors of AYA cancer matched to 23,999 AYAs without cancer enrolled in the Kaiser Permanente California health systems during 2004–2016. Of these, 950 survivors had ≥1 pregnancy during follow‐up through 2018. Hazard ratios (HR) and 95% confidence intervals (CI) for pregnancy were estimated using multivariable subdistribution hazard models accounting for competing risks. Relative risks (RR) and 95% CIs for pregnancy loss were calculated with multivariable Poisson regression with generalized estimating equations. Pregnancy was less common after AYA breast (HR = 0.57; 95% CI: 0.50, 0.66) or gynecologic cancer (HR = 0.55; 95% CI: 0.42, 0.73) compared to AYAs without cancer. Among AYAs with cancer, some alkylating and platinum chemotherapy agents, but not gonadotoxic radiation, were associated with a lower likelihood of pregnancy. Use of assisted reproductive technologies was not common, and 69% of pregnancies after AYA cancer resulted in live birth. Pregnancy loss was not statistically significantly elevated for any cancer type. Among survivors, pregnancy loss was more common at older ages, with smoking during pregnancy, and among those who received cyclophosphamide. Our findings inform reproductive counseling and prenatal care for reproductive age cancer survivors.

Importance:The role of supplemental coverage (eg, Medigap) in Medicare enrollment and disenrollment is understudied among beneficiaries with cancer. Understanding the association between initially selecting a supplement and switching plans is necessary to ensure adequate and affordable coverage for beneficiaries with high-cost health conditions. Objective:To evaluate Medicare plan switching by initial plan selection and history of cancer. Design, Setting, and Participants:This cohort study used data from the Health and Retirement Study, from 2008 to 2020. Respondents were aged 65 or 66 years at initial Medicare plan selection and completed 2 consecutive surveys. Analyses were conducted from November 2023 to October 2024. Exposures:Self-reported initial Medicare plan selection (traditional Medicare [TM] without supplemental coverage, TM plus supplemental coverage, or Medicare Advantage [MA]) and history of cancer. Main Outcomes and Measures:The primary outcome was self-reported Medicare plan switching in the 2 years after initial plan selection. Modified Poisson regression was used to assess the association between initial Medicare plan selection and plan switching. Models adjusted for baseline sociodemographic and health-related characteristics and were stratified by a history of cancer. Results:Among 2852 respondents aging into Medicare (1113 male [39.02%]), 1511 (52.98%) initially selected TM plus supplemental coverage and 358 (12.55%) reported a history of cancer. Less than one-third of beneficiaries (786 beneficiaries without a history of cancer [31.52%] and 106 beneficiaries with a history of cancer [29.61%]) switched coverage in the 2 years after initial plan selection. Most beneficiaries switched from TM without supplemental coverage to benefits with greater financial protections; 131 of 227 beneficiaries without a history of cancer (57.71%) switched to MA, and 18 of 27 beneficiaries with a history of cancer (66.67%) switched to TM plus supplemental coverage. Among beneficiaries without a history of cancer, initial selection of MA (adjusted risk ratio [aRR], 0.55; 95% confidence limit [CL], 0.47-0.64) or TM plus supplemental coverage (aRR, 0.63; 95% CL, 0.55-0.72) was associated with a lower probability of switching coverage compared with initial selection of TM without supplemental coverage. Findings were similar for beneficiaries with a history of cancer. Conclusions and Relevance:In this cohort study of older adults with and without a history of cancer, initial selection of MA or TM plus supplemental coverage was associated with a low likelihood of switching coverage. Given that benefits with greater financial protections may meet beneficiaries' evolving needs and preferences, policymakers should consider improving the adequacy of TM.

PURPOSE:To identify needs of metastatic breast cancer patients prior to starting a new systemic treatment. METHODS:Fifty patients with newly diagnosed, recurrent, or progressive metastatic breast cancer completed an electronic survey which included patient-reported outcome measures of function (PROMIS Cancer Function Brief 3D profile), quality of life (FACT-G), exercise (Godin Leisure-Time exercise questionnaire), and diet (REAP-S); demographic information; and self-reported use of or referral to specific resources at the cancer center prior to beginning a new systemic oncologic treatment. RESULTS:Prior to starting a new treatment for metastatic breast cancer, patients reported mild functional impairment (PROMIS Cancer Function Brief 3D profile mean score:42.1) and low quality of life (FACT-G: 50%) along with low diet quality (REAP-S mean score: 29). Fifty-two percent of patients were sedentary (Godin Leisure-Time exercise questionnaire) and major barriers to exercise were pain (38%) and fatigue (34%); however, patients expressed a high level of interest (86%) in improving their ability to tolerate cancer treatment by addressing these areas. CONCLUSION:Patients with new or recurrent metastatic breast cancer face health-related issues including sedentary behavior, poor diet, and limitations including pain and fatigue that can be addressed in prehabilitative efforts prior to starting a new oncologic treatment.

Background Hospital-acquired (HA) bleeding in medical inpatients is a serious complication with limited tools to predict risk. Objectives This study aimed to develop and validate risk assessment models (RAMs) for anatomic location-specific HA bleeding in medical inpatients using objective and routinely available risk factors. Methods Patients aged ≥18 years admitted to medical hospital services from 6 health systems and 15 hospitals in the United States between 2016 and 2020 for at least 1 midnight and without bleeding at admission were eligible for inclusion. Two health systems (10 hospitals) formed the development cohort, and 4 systems (5 hospitals) constituted the validation cohort. Bayesian Least absolute shrinkage and selection operator was used to develop anatomic site-specific RAMs. Results Among the development (153 707 admissions) and validation (137 460 admissions) cohorts, 5999 (3.9%) and 3282 (2.4%) HA bleeds occurred. RAMs had varied risk factors by anatomic bleeding location; for instance, older age was associated with genitourinary bleeding in men but not in women. Different cancer types were associated with different anatomic bleeding locations such as genitourinary cancers associated with genitourinary bleeding and gynecologic bleeding. The RAMs demonstrated good predictive performance for most anatomical bleeding locations; the C-statistic was ≥0.67 for all anatomic location bleeding in the development and validation cohorts and generally higher in the anatomic location specific RAMs. Conclusion These RAMs provide anatomic location-specific and sex-specific HA-bleeding risk stratification, addressing a critical gap in individualized risk assessment. Integration into clinical workflows could enhance patient safety and outcomes. Implementation studies are essential to maximize their clinical utility.

ABSTRACT:Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models' performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P < .0001) and worse OS (HR, 2.09; P < .0001). Bootstrap bias-corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

Social determinants of health (SDOH) are an increasingly recognized prognostic factor in patients undergoing hematopoietic cell transplantation (HCT) and chimeric antigen receptor-T cell (CAR-T) therapy. However, awareness among providers of their importance and appropriate evaluation of SDOH factors in transplant candidates is insufficient in standard clinical practice and in research. As part of a coordinated effort by 3 American Society for Transplantation and Cellular Therapy (ASTCT) Special Interest Groups, we have developed a general overview of SDOH in transplantation and cellular therapy (TCT) along with suggested best practices. We strongly encourage the assessment of SDOH pre-TCT by a trained member of the team as well as the development of a communication plan tailored to an individual patient's background. Other recommendations include the development and validation of longitudinal instruments for SDOH evaluation in patients undergoing TCT, with emphasis on those that use primary sources of information, the inclusion of SDOH in outcome and mortality benchmarks established by regulatory bodies, and the development of intervention strategies in the context of clinical trials.

Tacrolimus is a cornerstone of acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic cell transplant (allo-HCT) recipients. However, a narrow therapeutic index and high interindividual variability in pharmacokinetics (PK) make starting dose selection a major challenge in clinical practice. Data from two PK studies conducted at the University of North Carolina Medical Center (UNCMC) were used to develop an oral tacrolimus population pharmacokinetic (popPK) model specific to adult allo-HCT recipients. Monte Carlo simulations were performed to compare the likelihood of achieving the UNCMC institutional target trough concentration range (ITR) (5–10 ng/mL) on the day of transplant (D0) under the current institutional dosing protocol, dosing recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC), and model-derived dosing recommendations. In total, 290 allo-HCT recipients contributed a total of 906 PK samples to the final analysis. A two-compartment popPK model adequately described the PK data. Population typical values of apparent clearance (TVCL/F) for 70 kg individuals receiving reduced intensity conditioning were 0.33 L/h/kg for CYP3A5 poor metabolizers (PMs) and 0.70 L/h/kg for intermediate and normal metabolizers (IMs and NMs). The probability of the population-level average D0 trough concentration being within the UNCMC ITR under the current UNCMC weight-based dosing protocol, CPIC-based, and model-derived dosing strategies were estimated to be 37