Background HLA-matched sibling donor (MSD) HCT is the standard upfront therapy for younger patients with SAA. For older patients or those lacking an MSD, immunosuppressive therapy (IST) has historically been preferred, with alternative donor HCT reserved for relapsed/refractory (r/r) disease. BMT CTN 1502 demonstrated encouraging outcomes using haploidentical (haplo) HCT (1-year overall survival 81% in r/r SAA). The ongoing BMT CTN 2207 (CureAA) trial is evaluating upfront alternative donor (unrelated and haplo) HCT. To inform dissemination and implementation (D&I) strategies for CureAA, the BMT CTN D&I committee, in collaboration with the Aplastic Anemia and Myelodysplastic Syndrome International Foundation (AAMDSIF) and the North American Pediatric Aplastic Anemia Consortium (NAPAAC) surveyed hematology and HCT physicians in the United States on practice patterns and barriers to HCT and CureAA enrollment. Methods An online survey was distributed to >3500 members of AAMDSIF, NAPAAC, and CIBMTR (June-July 2025). Eligible respondents were physicians who manage SAA. Questions assessed referral practices, donor preferences, trial awareness, and perceived barriers to enrollment. Results Of 135 responses, 116 were eligible (47% adult, 53% pediatric; 78% BMT physicians; 93% transplant-center based). 52% reported their practice consists of >20% minority patients; 31% reported >5% of their patients are uninsured. Most (66%) see 1–5 SAA patients annually; 25% see 5-9 and 9% see ≥10.HLA typing at diagnosis is nearly universal (adult 90%, pediatric 93%). Among adult providers, 20% start IST upfront, 35% evaluate or refer for HCT, and the remainder use age cut-offs for HCT referral (commonly <40 years). MSD status influences HCT referral for 7% of adult and 27% of pediatric providers. Barriers to HCT referral and donor type preferences are shown in Figures 1&2.Regarding trial awareness, 64% know of BMT CTN 1502; 86% are somewhat/very likely to offer haplo if no MSD is available in r/r SAA. Seventy percent are aware of CureAA, but only 40% are likely to refer for the trial; 32% reported lack of local trial access and 18% are unsure. Reported barriers to CureAA enrollment include competing trials and concerns about alternative donor use, long-term HCT effects, protocol design, and trial accessibility. Respondents are more or equally likely to refer based on the use of conditioning with 4 Gy total body irradiation (84%) and post-transplant cyclophosphamide (93%) in the study. Conclusions This national survey shows support for HCT in r/r SAA and openness for upfront alternative donor HCT within a trial. A key limitation of the study is the low participation from community physicians who treat SAA. Addressing concerns about accessibility, donor source, and long-term toxicity are critical to improving CureAA accrual and future adoption of alternative donor HCT.

Background Infections account for over half of non-relapse mortality (NRM) among CAR T-cell recipients and NRM estimates are among the highest in patients with relapsed/refractory multiple myeloma (RRMM) receiving BCMA-directed CAR-T therapy. This CIBMTR study analyzed infection burden, risk factors, and outcomes and its impact on survival in 807 patients with RRMM receiving commercial idecabtagene vicleucel (ide-cel) from 3/2021 to 12/2023. Methods The primary endpoint was infection density for overall infections and for organism type within 100 days post-CAR-T infusion. Infection density was stratified into 2 distinct time intervals following CAR-T infusion: days 0-30 and days 31-100. Secondary endpoints included cumulative incidence of infections, infection-related mortality (IRM), and OS. Multivariable Cox proportional hazards models identified factors associated with infectious complications within 100 days post-CAR-T infusion. The impact of infections within 100 days of CAR-T on OS beyond 100 days following CAR-T infusion was also examined. Results Infections developed in 114 (14.1%) patients within 30 days and 226 (28%) patients within 100 days post-CAR-T infusion, resulting in an overall infection density of 0.49 per 100 patient-days and a 100-day cumulative incidence of 27.2%. Proportions of bacterial, viral, and fungal infections within 30 and 100 days of ide-cel infusion were 82 (10.2%), 50 (6.2%), 5 (0.6%), and 126 (15.6%), 125 (15.5%), and 8 (1%), respectively. The 100-day cumulative incidence of bacterial, viral, and fungal infections were 14.1%, 14.4%, and 0.9%, respectively. The 100-day IRM was 1.1%. With a median follow-up of 11.6 months, 222 (27.5%) patients died, and infection was the primary cause of death in 17 cases (7.7%).In MVA, KPS≤80 (p<0.001), infection prior to CAR-T requiring ongoing treatment after d+0 (p<0.001), CRS grade³2 (p=0.002), and severe ICANS (grade≥3) (p<0.001) were associated with an increased infection risk within 100 days post-infusion. Similarly, infection prior to CAR-T infusion requiring treatment after d+0 and grade≥3 ICANS significantly conferred a heightened risk for bacterial and viral infections within 100 days of CAR-T infusion.Number of infections within 100 days (HR, 2.36 for ≥2 vs. 0 infections; p<0.001), extramedullary disease or plasma cell leukemia (HR, 1.8; p=0.006), and prior BCMA-directed therapy (HR, 1.57; p=0.025) were independent risk factors for inferior OS beyond d+100 after CAR-T therapy. IVIG replacement post-CAR-T conferred a survival advantage (HR, 0.52; p<0.001). Conclusion The study results demonstrate a significant incidence of infections for a prolonged duration (14.1% in the first 30 days and 27% in the first 100 days) in patients undergoing ide-cel therapy. Viral infections increased beyond d+30 and multiple infections (≥2 episodes) were associated with inferior OS.

Background Patients and caregivers undergoing bone marrow transplantation (BMT) face overwhelming emotions, complex medical information, and significant uncertainty. Despite the availability of accurate medical details, families often report difficulty understanding how individual procedures and risks fit within the broader transplant trajectory. To address this gap, the Engraft Learning Network partnered with patients, caregivers, and providers to co-design a visual journey map that supports shared understanding and communication throughout the transplant process. Methods A human-centered design approach was used to co-create the Engraft Journey Map. Participants included patients (n=7), caregivers (n=11), and transplant providers (n=24) from multiple Engraft centers. Iterative design sessions captured lived experiences, pain points, and desired supports across the transplant journey. Themes were translated into visual elements depicting milestones, potential complications, and pathways from initial transplant discussions through long-term survivorship. Results The final Engraft Journey Map provides an accessible roadmap for patients and caregivers beginning with the decision to pursue BMT, extending through engraftment, recovery, complications, and survivorship. The map illustrates both expected milestones and potential detours, such as infection, graft-versus-host disease, and hospital readmissions. Families valued the map’s ability to show the “big picture” while remaining relevant at specific stages. Providers reported its utility as a communication aid during consent and follow-up discussions. The process of co-design ensured that the tool reflected real-world concerns, including emotional readiness, health literacy, and the need for clear orientation amidst uncertainty. Future Directions The next phase involves development of a digital platform embedding the journey map with stage-specific educational resources, patient videos, caregiver tips, and provider explanations. By grounding design in the voices of patients and caregivers, the Engraft Journey Map establishes a shared language for families and clinicians, transforming uncertainty into preparedness and strengthening trust across the care continuum. Conclusions Co-designing educational tools with patients, caregivers, and providers ensures they are not only informative but also supportive and empowering. The Engraft Journey Map exemplifies how patient- and caregiver-centered design can enhance communication, reduce overwhelm, and improve the transplant experience for families.

Background Frailty is a tool used to assess multisystem physiologic reserve and vulnerability in medically complex patients. Frailty has been used as a predictor of mortality in adult hematopoietic stem cell transplant (HSCT) programs and has led to the initiation of rehabilitation programs in HSCT patients to improve outcomes. In the pediatric population, frailty assessments are an emerging area of study. There is great potential for modifiable factors, such as nutrition, to help improve these outcomes. Objective To assess how nutrition interventions post HSCT impact a patient's frailty score from baseline to 100 days post HSCT (+/- 3 weeks). Methods From April 2022 to August 2025, frailty was assessed and scored on 70 pediatric and young adult patients (age range 3-27 years) at baseline and 100 days post HSCT (+/- 3 weeks) (Fig. 1). Frailty scores are composed of 5 factors including skeletal muscle mass, grip strength, 2-minute walk test, fatigue (PROMIS Score) and activity surveys (Lansky/Karnofsky). Nutrition interventions were then retrospectively analyzed at the time of initial hospital discharge post-HSCT and 100 days post HSCT (+/- 3 weeks). In this context, nutrition interventions included enteral feeds, parenteral nutrition, oral nutritional supplements, and/or appetite stimulants. To be recognized as part of the nutrition intervention cohort, patients needed to flag for a minimum of one of the described nutrition interventions at initial hospital discharge from HSCT and/or 100 days post HSCT. The baseline frailty score and day +100 frailty score were then analyzed based on utilization or absence of nutritional intervention. Results Our data revealed that average frailty scores worsened from baseline (median 2.6, range 0-7) to day +100 (median 3.1, range 0-7) for patients who did not have nutrition interventions at the analyzed time points; p<0.01 (Fig. 2B). In the group who did receive nutrition interventions, there was a decrease in the lower quartile frailty score from baseline (inner quartile range of 2-4) to day +100 (inner quartile range of 1-4), indicating an improvement in frailty, although this did not reach statistical significance (Fig. 2C). Additionally, we observed intra-patient changes in frailty score from baseline to day 100 in patients with nutritional interventions (n=39) (Fig. 3B) and without nutritional interventions (n=31) (Fig. 3A). It is important to remember each patient's frailty score could be impacted by additional factors outside of nutrition interventions, but this was not analyzed in this investigation. Conclusion Without nutritional interventions post HSCT, patients have an increased likelihood of becoming more frail at Day 100. These findings support early, proactive nutrition engagement as part of post-HSCT recovery programs.

Background Chronic graft-versus-host disease (cGVHD) affects ∼40% of allogeneic transplant recipients and is a major cause of morbidity and mortality. Although NIH consensus criteria standardize definitions, their application in routine practice is inconsistent. Early recognition is essential, yet screening and documentation vary widely. The Engraft Learning Network conducted a multicenter assessment to characterize this variation and identify opportunities for standardization across pediatric and adult transplant programs. Methods 30 structured interviews were completed with clinician representatives from 10 Engraft Learning Network centers (2 adult, 8 pediatric). Interviews explored timing and frequency of screening, organ-specific review of systems (ROS) and physical examinations, documentation approaches, and interpretation of findings. Each interview was transcribed, summarized for provider validation, and visualized in heat maps to illustrate cross-center variability. Results Marked heterogeneity was observed across all domains of cGVHD screening (Figure). Assessment schedules ranged from weekly to as-needed; 53% performed monthly evaluations in the first six months post-transplant, and only 37% continued quarterly assessments beyond one year. Documentation methods varied, 20% used structured flowsheets, 33% used dot phrases, and 47% relied on free-text notes. Only 57% documented NIH organ-based cGVHD scoring, and 10% incorporated the Lee Symptom Scale. Skin was universally assessed, though only 13% performed comprehensive exams. Oral evaluations were common, but comfort identifying oral cGVHD was modest (median 6/10). Ocular screening was often limited (17% not routinely assessed). Pulmonary evaluations were standard, but PFT intervals differed. Gastrointestinal and genitourinary reviews showed the greatest inconsistency, fewer than half routinely screened for dysphagia or GU symptoms. Musculoskeletal assessments were incomplete at many centers, and rare manifestations (e.g., neuropathy) were seldom addressed (<10%). Conclusions cGVHD screening practices vary widely in timing, documentation, and completeness across centers, contributing to delayed recognition and inconsistent management. These findings highlight the need for a standardized, evidence-informed approach with defined domains, assessment intervals, and structured documentation. Engraft, a collaborative of pediatric and adult transplant programs advancing outcomes through shared learning, data-driven research, and co-designed quality improvement, is developing this bundle to reduce variability, enable earlier detection, and foster cross-center learning. By translating guidelines into practical, patient-centered workflows, this initiative aims to reduce morbidity and improve quality of life and long-term outcomes for transplant recipients.

There are no biomarkers or therapies for graft rejection after hematopoietic stem cell transplant (HSCT) due to a limited mechanistic understanding of this event. We hypothesized that interferon activation from recipient cells drives donor cell elimination during graft rejection. To test this hypothesis, we studied plasma proteomes of HSCT recipients with graft rejection in comparison to febrile HSCT recipients who engrafted. Leading differentially expressed proteins (DEPs) included CXCL11 (q=2e-5) and CXCL10 (q=3.4e-3). The most highly enriched pathway was interferon gamma response (q= 8.59e-10). Interferon gamma, tumor necrosis factor (TNF) and interferon alpha were also the leading upstream regulators of DEPs. Drug network interactomes for interferon gamma and TNF inhibitors confirmed these therapies may inhibit activated pathways. We then performed single cell RNAseq on peripheral blood mononuclear cells (PBMCs) from a graft rejection patient and compared PBMCs at the time of rejection to a prior timepoint after initial engraftment. PBMC transcriptomes were separated by donor (female) and recipient (male) origin, revealing a marked increase in recipient NK cells (3.5% versus 83.7%) and recipient effector memory T-cells (8% versus 91.8%) during rejection. Donor classical monocytes during rejection showed ferroptosis pathway enrichment, an interferon-mediated form of cell death. To our knowledge, this is the first single cell RNAseq study in humans to confirm recipient NK cell and T-cell resurgence during graft rejection after HSCT. We additionally identified promising biomarkers (CXCL11, CXCL10, LAG3), a potential mechanism of donor cell death (ferroptosis) and targetable immunologic pathways (interferon gamma, TNF) meriting further study.

Introduction Improving outcomes in transplant and cellular therapy (TCT) requires both high-quality data and real-time access for clinicians, researchers, and administrators. Traditional registry reporting limits timely feedback and cross-center collaboration due to reporting delays, inconsistent data requirements, and compliance hurdles. The Engraft Learning Network developed an interactive, multi-center informatics platform to enable rapid, data-driven quality improvement (QI) and to serve as the foundation for all future Engraft initiatives. Objective To demonstrate how a multi-center, self-service Power BI dashboard enables real-time, data-driven quality improvement in transplant and cellular therapy through secure, scalable, and collaborative analytics. Methods A Power BI–based self-service dashboard was developed to integrate Engraft Registry data from 13 adult and pediatric centers. Data domains include patient demographics, therapies, central venous catheter (CVC) characteristics, line days, and complications. Visualizations include pie charts for distributions, box-and-whisker plots for outcomes, and statistical process control (SPC) run charts to track improvement over time. Users can filter to their own center or view aggregated network results for benchmarking and collaborative discovery. Key elements include:• A secure, audited data environment with regular integrity checks.• An honest broker process to ensure compliance and data governance.• Structured governance enabling cross-center data use and scalability for future projects. Results The dashboard is deployed across Engraft centers and currently supports a network-wide CVC line removal initiative. Fig.1 displays patient demographics across centers, highlighting real-time visualization of registry data. Fig.2 shows SPC run charts tracking CVC line days per patient day, allowing centers to identify variation and improvement opportunities. This same infrastructure serves as the core analytic platform for future Engraft studies, including cGVHD screening. Early user feedback highlights the value of interactive analytics for engaging clinical teams and reducing reliance on static reports. Conclusions The Engraft Registry Power BI dashboard establishes a scalable, multi-center informatics foundation to accelerate collaborative QI in TCT. By integrating registry data with flexible visualization, it enhances decision-making, operational efficiency, and network-wide learning. Future projects, including cGVHD, infection prevention, and survivorship, will build directly on this shared infrastructure to sustain continuous improvement across the Engraft Network.

BACKGROUND:Pediatric oncologic and hematopoietic stem cell transplant (HSCT) recipients are vulnerable to life-threatening illnesses. Extracorporeal membrane oxygenation (ECMO) support as a rescue modality in this population remains controversial. The aim of this study is to describe a large single-center experience with complications and outcomes for pediatric patients with an oncologic diagnosis and/or HSCT on ECMO, and to compare survival outcomes in a smaller multicenter cohort. PROCEDURE:This was a descriptive and comparative observational study. The descriptive analysis, a large single-center experience, examined bleeding complications, infectious rates, and survival outcomes in patients under 18 years old with an underlying oncologic diagnosis and/or HSCT on ECMO. In a small multicenter cohort, the comparative analysis evaluated survival outcomes with respiratory failure in the presence and absence of ECMO. Children's Mercy Kansas City served as the ECMO cohort; Cincinnati Children's Hospital Medical Center served as the matched non-ECMO cohort. RESULTS:Twenty-two ECMO patients were included for the descriptive analysis. Most patients had severe thrombocytopenia, with half developing bleeding complications. Nearly half of patients were neutropenic, and the majority were lymphopenic at ECMO cannulation, with only one neutropenic patient developing a new infection. Twenty-two patients were included (n = 11 ECMO; n = 11 non-ECMO) for the comparative analysis. Calculated oxygenation indices for each cohort were 32.8 and 37.5, and peak inspiratory pressures were 35.5 and 37. The ECMO cohort had 45% of patients survive to hospital discharge compared to 27% of non-ECMO controls (p = 0.659). CONCLUSIONS:The findings of this study suggest that bleeding complications and incidence of infections on ECMO are comparable to the general ECMO population. ECMO utilization in pediatric oncologic and HSCT patients with respiratory failure did not offer a survival advantage to conventional PICU management in the setting of a respiratory illness. CLINICAL TRIALS REGISTRATION NUMBER:NCT07712835.

Background Psychosocial support is vital for patients and caregivers undergoing hematopoietic stem cell transplantation (HSCT), yet the availability and visibility of mental health resources vary widely across centers, leading to underutilization, delayed referrals, and inconsistent patient experiences. Methods We conducted a multi-center analysis comparing provider-reported perceptions of mental health resources (n=24 providers) with verified inventories from program administrators (n=16) across Engraft Learning Network centers (n=10). Surveys captured data on available staff (social workers, psychologists, psychiatrists), service types (counseling, support groups, psychiatry, caregiver programs), referral practices, and perceived barriers. Alignment between perceived and actual resources was assessed to identify gaps in awareness, access, and integration. Results All participating providers (24/24, 100%) agreed that patients and caregivers undergoing hematopoietic stem cell transplantation require mental health support. Verified data from administrators (n=16) across 10 Engraft centers showed all had social work and chaplaincy services, while 56% had embedded psychology and 44% had psychiatry support. Nine centers reported social workers dedicated exclusively to transplant, and seven shared coverage with other programs. Provider perceptions differed notably from verified availability. Nearly all providers (96%) believed individual counseling and psychiatric services were accessible, but only 53% recognized caregiver or peer-support programs. Actual inventories indicated that 69% of centers offered caregiver programs and 80% provided peer mentorship, revealing persistent awareness gaps. Common barriers included caregiver time constraints or competing responsibilities (82%), lack of awareness of available services (68%), and language or cultural barriers (59%). Financial and insurance barriers, long wait times, and stigma were also frequently cited. The most needed resources were additional psychologists and psychiatrists (75%), caregiver-specific programs (67%), and structured peer or group support (58%). Providers emphasized that shorter wait times, clearer referral pathways, and better integration of psychosocial care into transplant workflows would improve access. Direct communication from mental health staff (71%) and standardized referral flowcharts (63%) were viewed as most effective for improving awareness and coordination. Conclusions Significant gaps exist between available psychosocial resources and provider awareness across centers. Standardized communication, onboarding, and referral workflows may close this perception–reality gap. Through shared data and collaboration, the Engraft Network offers a model for improving psychosocial care integration in transplant practice.

Infections are common after chimeric antigen receptor (CAR) T-cell therapy and contribute to morbidity and mortality. While well characterized with CD19 CAR T-cells, data related to infections with B-cell maturation antigen (BCMA) CAR T-cell therapy are limited. This study aims to characterize the burden, patterns, risk factors, and clinical impact of infections on outcomes in patients with relapsed/refractory multiple myeloma (RRMM) treated with idecabtagene vicleucel (ide-cel). In this real-world analysis, we evaluated 807 patients with RRMM who received ide-cel after ≥4 prior lines of therapy between March 2021 and December 2023, using the Center for International Blood and Marrow Transplant Registry database. The infection density within 100 d post-ide-cel was 0.49 for any infection, and 0.23, 0.22, and 0.012 for bacterial, viral, and fungal infections, respectively. Bacterial infections predominated during the first 30 d post-infusion, whereas viral infections were more prevalent between day +30 and d +100. After a median follow-up among survivors of 11.6 months, 364 patients relapsed and 222 died, translating into a 1-yr progression-free survival of 46.5% and overall survival (OS) of 67.3%. Disease progression was the leading cause of death, followed by infections. Infection-related mortality was 1.1% at d +100. On multivariable Cox regression, baseline infection history prior to ide-cel, poor performance status (KPS<80), grade≥2 cytokine release syndrome, and grade≥3 neurotoxicity were independent predictors of infection. Recurrent infections (≥2 events) within 100 d and relapse within 100 d after ide-cel were associated with inferior OS. Infections are common and can result in inferior outcomes after ide-cel, underscoring the importance of risk stratification, surveillance, and stringent infection prevention strategies to optimize outcomes.

Topic Significance & Study Purpose/Background/Rationale Patients undergoing hematopoietic stem cell transplant (HSCT) require semi-permanent central venous catheters (CVCs) for chemotherapy, nutrition, medications, and blood products. Prolonged use increases the risk of infections, thrombosis, and mechanical complications, while adding psychosocial and financial burdens for patients and families. The Engraft Learning Network, a collaboration dedicated to improving outcomes for transplant and cellular therapy patients, has identified timely CVC removal as a key opportunity to improve outcomes and reduce healthcare costs. Engraft recognizes that the risk and financial burden associated with CVCs accumulate over time and should be factored into decisions regarding removal timing. Methods, Intervention, & Analysis Between January and March 2025, we directly observed 15 CVC dressing changes at Cincinnati Children’s Hospital Medical Center (CCHMC), where two-nurse dressing changes are standard of care. We recorded the duration of dressing and cap changes and daily flushing and paired observed times with supply costs and standard nursing wage data to calculate maintenance costs. In parallel, an Engraft-wide nursing survey (n = 15) was conducted to evaluate the standard of care for dressing and cap changes across 10 centers. Findings & Interpretation For a double-lumen tunneled CVC:• Dressing changes: required 20–46 minutes (mean ∼32 minutes) of nursing time, averaging $26.78 in labor and $28.47 in supplies per change.• Cap changes typically took <5 minutes, with $4.17 in labor and $19.91 in supplies per weekly change.• Daily flushing: averaged $13.70 per day using pre-filled saline and heparin syringes.The total monthly cost of CVC maintenance was approximately $664 (dressing and cap changes plus flushes) for one nurse, varying by ±25% depending on supply contracts.Survey data demonstrated substantial variation in CVC maintenance practices across Engraft centers (Figure 2), including differences in dressing change frequency, cap change intervals, and staffing models. Extending dwell time by one week (delayed removal) incurs roughly $150 additional maintenance costs per patient. Discussion & Implications CVC maintenance requires substantial time, supplies, and coordination. While costs vary across centers, even conservative estimates highlight a clear economic and clinical rationale for timely CVC removal. These estimates likely underestimate the burden, as they do not include the costs associated with complications such as infection, thrombosis, or broken lines, nor the psychosocial burden placed on families. Engraft is evaluating how standardizing removal timing can reduce complications, improve quality of life, and lower healthcare costs across participating centers. Identifying the clinical “sweet spot” for removal, balancing safety with cost and psychosocial burden, represents a meaningful and actionable quality improvement goal for the network.

Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a life-threatening hyperinflammatory toxicity distinct from cytokine release syndrome (CRS) and neurotoxicity following chimeric antigen receptor T-cell (CAR-T) therapy. In a single-institution retrospective cohort of pediatric and young adult patients with relapsed or refractory acute B-lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel between November 2023 and April 2025, two of 12 patients (17%) developed IEC-HS after CRS resolution, marked by recurrent fever, coagulopathy, hepatic dysfunction, cytopenias, and profound elevations in CXCL9, IL-18, and soluble C5b-9. Treatment with emapalumab led to rapid clinical and biomarker improvement. These findings support IEC-HS as an interferon-γ-driven syndrome and suggest targeted IFN-γ blockade as a potentially effective therapeutic strategy.

Introduction Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), driven by endothelial injury and complement activation. Eculizumab, a terminal complement C5 inhibitor, improves survival in high-risk TA-TMA, yet one-third of patients fail to respond. Objective To determine mechanisms of eculizumab non-response and early predictors of outcome in TA-TMA that are critical for improving therapy. Methods We studied 90 children and young adults with high-risk TA-TMA, comparing eculizumab responders (n=60) and non-responders (n=30). All HSCT recipients were prospectively screened for TA-TMA. TA-TMA risk group and response to eculizumab was determined based on published criteria (Fig1). All patients with high-risk TA-TMA received PK/PD-guided eculizumab dosing. We performed novel PK/PD modeling to determine complete complement blockade (“equilibrium”). Complement blockade, PK/PD dynamics, biomarker trajectories for sC5b-9, CXCL9, ST2, proteinuria by random urine protein/creatine ratio (rUPCR), and outcomes were compared in responders and non-responders. Results Non-responders displayed greater systemic organ injury and worse survival despite optimized eculizumab dosing and PK/PD monitoring (Fig 2A). PK/PD modeling confirmed that complement blockade can be achieved with intensified dosing, but steady blockade state (equilibrium) requires approximately six weeks of therapy, underscoring that short-term biomarker normalization is not sufficient to declare response (Fig 2B). Importantly, non-responders exhibited persistently elevated rUPCR and rising ST2 despite suppression of sC5b-9, indicating ongoing complement-independent endothelial injury. Longitudinal biomarker profiling showed that non-responders had progressive CXCL9 elevation despite sC5b-9 control, and that adding IFNγ blockade with emapalumab improved eculizumab PK/PD, accelerated complement suppression, and enhanced survival, underscoring the pathogenic role of the complement-interferon loop (Fig3). We showed that elevated sC5b-9 is associated with TA-TMA risk, higher therapy needs and poor outcomes, whereas comprehensive profiling of other complement components did not differentiate responders, and normal C3/C4 values did not exclude TA-TMA highlighting the need for functional biomarkers. Conclusion These findings reveal that eculizumab non-response reflects complement independent persistent endothelial injury. Early monitoring of ST2, CXCL9, rUPCR, may identify patients at risk for suboptimal eculizumab response and guide precision therapies that can be integrated with complement blockade. Such strategies will be essential to improve survival and prevent irreversible vascular injury in high-risk TA-TMA.

Background Hematopoietic stem cell transplantation (HSCT) is a complex process to treat a variety of diseases among pediatric patients, but it can produce significant side effects, many of which occur in the oral cavity. Despite the importance of oral health in this population, there is limited research related to oral health practices at pediatric HSCT centers. Objective This study aimed to assess current practices and recommendations regarding dental care provided to children undergoing HSCT in the United States. Methods A standardized survey was developed by a multi-disciplinary team (pediatric dentists, transplant physicians, and oral medicine specialists) and sent to the 83 pediatric HSCT centers in the United States. Responses were collected and analyzed to characterize oral health practices, availability of dental resources and challenges encountered in patient care. Three attempts were made in total to collect the survey responses. Results We received responses from physicians at 52 centers (62%). Survey responses demonstrated that patients at most centers receive a comprehensive dental evaluation prior to HSCT (n=51, median response of 96.5%); at least 77% (n=40) of HSCT centers require necessary dental treatment be completed prior to HSCT, and 87% (n=45) have access to a dentist with hospital privileges to evaluate and provide consultation for patients. No differences were identified between access to dentists with hospital privileges based on the geographic location of centers (p=.13). Nearly all centers (96% n=50) recommend daily toothbrushing following HSCT, with daily chlorhexidine rinses (61% n=32) being the second most common oral hygiene adjunct. Patient and caregiver education is routinely provided, most often through verbal instruction (77% n=40). Reported challenges include limited availability of dental treatment (54% n=28) as well as management of chronic graft versus host disease (52% n=27) and mucositis (37% n=20). Conclusions While these challenges remain, the results of this study demonstrate that dental care and oral hygiene are being well integrated into many treatment centers, with patients routinely receiving examinations and necessary treatment prior to transplantation with follow-up care available from dental professionals at transplant centers.

Introduction The Center for International Blood and Marrow Transplant Research (CIBMTR) has envisioned a “virtual consortium” to enhance the value of its registry by securely consolidating Data Back to Center (DBtC) files across institutions. This initiative enables multi-center collaboration for quality improvement (QI) and research, improving data quality while reducing reporting burden—advancing the principle of “enter once, use many times.” The Engraft Learning Network is among the first to implement this vision, creating a shared analytic environment for collaborative learning in transplant and cellular therapy (TCT). Objectives To demonstrate how integrating CIBMTR DBtC data enhances registry accuracy and enables collaborative quality improvement in transplant and cellular therapy. Methods With data use agreements, IRB approvals, and site authorization, CIBMTR consolidated DBtC files from Engraft centers. Files were securely transmitted to the Engraft Data Coordinating Center under an honest-broker model and integrated into the Engraft Registry to supplement manually entered data and enable systematic quality checks. Discrepancies between registry and DBtC data were assessed for infusion date, birth date, sex, race, and date of death, with mismatches adjudicated at Cincinnati Children’s (CCHMC). Chronic GVHD (cGVHD) variables—diagnosis date, maximum grade, and contact date—were summarized by mean and median time to diagnosis and maximum grade by severity. Race data from DBtC were also incorporated to enhance analyses and support equity-focused evaluation. Results Across eight centers, 515 Engraft transplants matched pre- and post-TED DBtC data. Infusion date discrepancies occurred in 35 cases (7%), all from CCHMC, with DBtC correct in each. Birth date and sex discrepancies (n=9 each) and date-of-death discrepancies (n=3) were mostly corrected in DBtC. Race discrepancies were rare, though missing or unknown race was common (20 Engraft records missing values in DBtC; 49 missing in DBtC). Median time to cGVHD diagnosis ranged from 168–228 days post-transplant, with time to maximum grade and contact summarized in Figures 1–2. Conclusions Integrating CIBMTR DBtC data within Engraft improved registry accuracy, completeness, and interoperability while reducing burden. This approach demonstrates the feasibility of securely leveraging DBtC data for multi-center QI and research, advancing CIBMTR’s vision of maximizing registry impact across the TCT community.

Background Central venous catheters (CVCs) are almost universally needed during transplant and cellular therapy (TCT) but are associated with complications including bloodstream infections (BSIs) and thrombosis. These complications lead to reduced quality of life and increased healthcare costs, adding burdens to patients and caregivers. Striking the right balance in keeping a CVC in place for the appropriate length of time is essential. The Engraft Learning Network is a unique quality improvement (QI) collaboration between 13 adult and pediatric transplant and cellular therapy (TCT) centers dedicated to QI and improving the lives of patients and their caregivers. Methods Participating centers co-designed the learning network’s inaugural initiative between January and July 2024 with the goal of promoting timely CVC removal. A key driver diagram identified interventions including standardized monthly assessments of line necessity for all post TCT patients, consistent post-transplant CVC evaluations, documentation of center-specific practices, and structured cross-center learning as means to reduce line days. The outcome measure was the number of CVC days (numerator) per 100 patient days (denominator) within the first 365 days post-transplant. Exclusion criteria included relapse, transfer, or death. Baseline data of allogenic TCT were displayed beginning January 2022 to emphasize pre-intervention stability and highlight the special-cause variation observed beginning in 2024. Statistical process control (SPC) charts were used to evaluate trends and, control limits, and variance over time. Results Across the Engraft Network, approximately 5,000–6,000 CVC days are recorded each month. Since project initiation, the mean rate has decreased from 68 to 58 CVC days per 100 patient days—a 15–20% improvement. This corresponds to an estimated 750–1,000 fewer CVC days each month and 9,000–12,000 fewer annually. Post-intervention SPC charts show a clear downward shift in the mean with narrower control limits, reflecting reduced variability and greater process reliability across centers (Figure 1). The most compelling special-cause variation emerged beginning in March 2025. As centers started to discuss and implement the assessment tool, there was a downward trend of CVC days seen and this trend continued after fully implementing the standardized monthly assessments. Discussion This multi-center QI initiative demonstrates that structured, shared learning can lead to meaningful and sustained reductions in CVC retention after TCT. The decline in both mean CVC days and data variability underscores a transition toward more standardized practice patterns and safer, more consistent, and financially aware post-transplant care that will improve the quality of life for patients and caregivers.

Background Chronic graft-versus-host disease (cGVHD) affects up to half of allogeneic transplant recipients and remains a leading cause of late morbidity and mortality. Early detection and standardized assessment are essential to improving outcomes and advancing biomarker validation. In collaboration with the CIBMTR and the ASTCT Committee on Informatics, the Epic HCT EMR User Group (including providers, Epic developers, and registry experts) created validated Epic “Foundation” tools for transplantation, including the NIH-based cGVHD flowsheet (ID: 1150000021, ONCBCN Chronic GVHD). This functionality enables structured, longitudinal documentation using standardized data elements mapped to CIBMTR Common Data Elements, supporting interoperable data sharing and multicenter research. Methods The Engraft Learning Network conducted structured interviews with 30 providers across 10 centers to assess awareness, workflow, and documentation practices for cGVHD. A practical, low-effort implementation framework was developed based on findings, emphasizing clinical usability and minimal analyst effort. Key steps included:1. Flowsheet activation via Epic Support (ID 1150000021).2. Note integration using SmartPhrases/SmartLists for NIH organ scoring.3. Reporting Workbench dashboards for completion tracking and cross-site comparison.4. Provider training to align documentation with NIH criteria and research needs. Results At the outset of this initiative, only 2 of 13 Engraft centers had activated the Epic cGVHD flowsheet. Implementation is now progressing across the remaining 11 centers, with several additional transplant programs outside Engraft preparing to adopt the framework. Although outcome data are not yet available, early feedback highlights the tool’s simplicity, minimal technical burden, and strong potential for rapid dissemination across Epic-based institutions. Conclusions Epic’s cGVHD flowsheet, developed by the national HCT EMR User Group, provides a validated, interoperable foundation for standardized cGVHD documentation and longitudinal tracking. Figure 1 offers a ready-to-use roadmap that enables any transplant center to implement the tool with minimal resources, improving consistency, reducing variability, and positioning programs for future data-driven research on early detection, severity scoring, and biomarker validation across the transplant continuum.

ABSTRACT:Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. In a multivariable analysis, receipt of ≥3 lines of therapy before tisa-cel (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.13-3.08; P = .015), any-grade cytokine release syndrome (HR, 1.78; 95% CI, 1.17-2.71; P = .007), and lack of neutrophil recovery (HR, 2.63; 95% CI, 1.47-4.69; P = .001) were associated with an increased risk for any infection. Similar associations were observed for bacterial infections, with the addition of younger age as an adverse risk (<6 vs 6-15 years; HR, 2.38; 95% CI, 1.23-4.61; P = .01). Risk factors for viral infections included increasing age (1-year increase; HR, 1.05; 95% CI, 1.01-1.09; P = .016), prior history of any infection (HR, 2.76, 95% CI, 1.40-5.46; P = .004), and prior hematopoietic cell transplant (HR, 2.10; 95% CI, 1.18-3.71; P = .011). D100 infection-related mortality (IRM) rate was low at 0.2% (95% CI, 0.0-0.8). In this multicenter real-world study, we observed a high incidence of infectious complications but a low IRM following tisa-cel for R/R B-ALL.