Importance Hispanic and non-Hispanic Black (hereafter, Black) children with acute myeloid leukemia (AML) have historically experienced worse survival outcomes compared with non-Hispanic White (hereafter, White) children. Understanding specific intermediate pathways underlying these outcome disparities is a critical step to directing interventional efforts and resources. Objective To compare survival outcomes by race and ethnicity in a large contemporary cohort of pediatric patients with AML and to examine presentation acuity, frontline organ toxic effects, and relapse as potential mediators of any observed outcome disparities. Design, Setting, and Participants This retrospective cohort study was analyzed from April 2025 to January 2026 and included 13 US children’s hospitals across 10 states participating in the Real-World Epidemiology of Acute Leukemia-AML cohort. Participants included children treated for de novo AML from January 2011 through May 2024. Exposure Race and ethnicity (Black, Hispanic, and White). Main Outcomes and Measures The main outcome was overall survival (OS), defined as the time from AML diagnosis until death from any cause. Results The study cohort included 773 children (median [IQR] age, 9 [2-14] years; 402 males [52.0%]), of whom 125 (16.2%) were Black, 237 (30.7%) were Hispanic, and 411 (53.2%) were White (median [IQR] follow-up, 51.2 [25.7-86.9] months), treated for de novo AML. Among the patients, Black (5-year OS, 61.1% [95% CI, 52.6%-71.0%]; adjusted hazard ratio [AHR], 1.55 [95% CI, 1.26-1.91]) and Hispanic (5-year OS, 65.4% [95% CI, 58.9%-72.5%]; AHR, 1.32 [95% CI, 1.03-1.68]) children had worse OS compared with White children (5-year OS, 70.0% [95% CI, 65.2%-75.1%]). Compared with White patients, Black patients had increased risk of higher cardiovascular (adjusted risk ratio [ARR], 2.09 [95% CI, 1.23-3.56]), respiratory (ARR, 1.36 [95% CI, 1.05-1.77]), and renal (ARR, 3.08 [95% CI, 1.02-9.32]) acuity at presentation. There were no statistically significant increases in severe frontline organ toxic effects or relapse rates by race and ethnicity. Cardiovascular acuity (AHR, 1.83 [95% CI, 1.51-2.22]) and respiratory acuity (AHR, 1.43 [95% CI, 1.15-1.77]) at presentation were independently associated with all-cause mortality. Cardiovascular acuity (proportion mediated, 14%) and respiratory acuity (proportion mediated, 8%) at presentation partially mediated the total absolute survival difference between Black and White children. Conclusions and Relevance In this cohort study of pediatric patients with AML, differential cardiovascular and respiratory acuity at presentation were partial mediators of outcome disparities for Black children with AML. Other intermediates along the care continuum should be identified to account for the remainder of the observed outcomes and to prioritize focus areas for interventional efforts to mitigate the survival differences.

Background: Post‑relapse survival of pediatric acute myeloid leukemia (AML) remains poor and there is a paucity of data to inform relapse regimen selection. We sought to describe the treatment landscape for first AML relapse and compare effectiveness of prevalent salvage regimens. Methods: We conducted a retrospective cohort study using the REAL‑AML dataset including pediatric patients with first relapse of AML treated at 13 US pediatric institutions from 2011–2023. Primary analyses compared overall survival (OS) by regimen backbone and by receipt of gemtuzumab ozogamicin (GO). Secondary outcomes included end‑of‑re‑induction clinical remission (CR) and measurable residual disease‑negative CR (MRD‑CR). Findings: 247 patients met inclusion criteria (median post‑relapse follow‑up 28 months). Two‑year OS was 45.6% (95% CI 38.8–52.2%). Thirty‑nine unique re‑induction regimens were used; 21.9% received non‑intensive regimens. Among 173 patients eligible for comparative analyses, there were no statistically significant differences in OS or end‑re‑induction responses by backbone chemotherapy. Point estimates suggested benefit with addition of anthracycline to fludarabine/cytarabine±G‑CSF for OS (aHR of death vs FLA(G) = 0.38, 95%CI 0.11–1.38), and for CR and MRD‑negative CR (aPR = 1.32 and 1.34, respectively). Incorporation of GO increased likelihood of CR (aPR 1.25, 95%CI 1.01–1.54) and MRD‑negative CR (aPR 1.48, 95% CI 1.07-2.06) but did not improve OS (aHR 1.12, 95%CI 0.57–2.19). Interpretation: These contemporary, real-world data provide updated benchmarks for pediatric first‑relapse AML outcomes. Use of GO in relapse may improve end‑induction response but survival benefit remains unproven. Prospective evaluation and further work to personalize therapy are needed.

Post-relapse survival of pediatric acute myeloid leukemia (AML) remains poor and there is a paucity of data to inform relapse regimen selection. We sought to describe the treatment landscape for first AML relapse and compare effectiveness of prevalent salvage regimens. To do this, we conducted a retrospective cohort study using the REAL-AML dataset including pediatric patients with first relapse of AML treated at 13 US pediatric institutions from 2011-2023. Primary analyses compared overall survival (OS) by regimen backbone and by receipt of gemtuzumab ozogamicin (GO), without an a priori hypothesis about a specific regimen efficacy. Secondary outcomes included end-of-re-induction clinical remission (CR) and measurable residual disease-negative CR (MRD-CR). 247 patients met inclusion criteria (median post-relapse follow-up 28 months). Two-year OS was 46% (95% CI 39-52%). Thirty-nine unique re-induction regimens were used; 22% received non-intensive regimens. Among 173 patients eligible for comparative analyses, there were no statistically significant differences in OS or end-re-induction responses by backbone chemotherapy. Point estimates suggested benefit with addition of anthracycline to fludarabine/cytarabine±G-CSF for OS (aHR of death vs FLA(G) = 0.38, 95%CI 0.11-1.38), and for CR and MRD-negative CR (aPR = 1.3, for both). Incorporation of GO increased likelihood of CR (aPR 1.3, 95%CI 1.0-1.5) and MRD-negative CR (aPR 1.5, 95% CI 1.1-2.1) but did not improve OS (aHR 1.1, 95%CI 0.6-2.2). These contemporary, real-world data provide updated benchmarks for pediatric first-relapse AML outcomes. Use of GO in relapse may improve end-induction response but survival benefit remains unproven. Prospective evaluation and further work to personalize therapy are needed.

Cytomolecular features critical for risk-stratified treatment determination in pediatric acute myeloid leukemia (AML) were expanded in Children's Oncology Group (COG) Phase III trial AAML1831 based on previous trials. It remains unknown whether the cytomolecular risk profiles are generalizable to the real-world. We addressed this knowledge gap using a nationally representative real-world cohort of 913 pediatric AML patients. Distributions of cytomolecular risk profiles and individual markers were comparable for trial-enrolled and non-enrolled patients, as well as across social drivers of trial enrollment (race/ethnicity, language, insurance, acuity). Compared to patients with only favorable cytomolecular markers (4-year overall survival [OS] = 89.48%; 95% CI = 84.46% to 92.95%), patients with both favorable and unfavorable (hazards ratio [HR] = 2.49, 95% CI = 1.18 to 5.23), neutral (HR = 4.33, 95% CI = 2.75 to 6.82), and only unfavorable (HR = 5.80, 95% CI = 3.70 to 9.11) markers all had increased hazards of death. Cytomolecular risk informed by trial data appears to be generalizable to the real-world setting in pediatric AML.

Background Invasive fungal disease (IFD) is a leading cause of morbidity and mortality in patients with hematologic malignancies. The most recent practice guidelines, last updated in 2020, recommend using a mold-active azole or echinocandin when antifungal prophylaxis is warranted; however, there has historically been a lack of standardized prescribing practices at our institution. Objective This study’s primary aim is to characterize our institution’s current prescribing patterns by comparing the incidence of IFD among pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with or without antifungal prophylaxis. Methods This single-center, retrospective chart review evaluated patients with ALL or AML treated at Arkansas Children’s Hospital from January 1, 2020, to August 31, 2023. Secondary analyses included evaluating IFD in high-risk patients, incidence of adverse events, and use of therapeutic drug monitoring. Descriptive statistics were calculated and statistical significance was determined using chi-square, Fisher’s exact, and Mann-Whitney U tests. Results A total of 114 patients were included, with 54 patients receiving antifungal prophylaxis. Patients receiving antifungal prophylaxis with fluconazole had a higher incidence of IFD than other prophylaxis agents and no prophylaxis (P < 0.01). Among high-risk patients, 62.9% received antifungal prophylaxis. There was a lower incidence of IFD in those who received mold-active prophylaxis than those who did not (17.4% vs. 35.1%, P = 0.03) and in those who received guideline-directed prophylaxis than those who received fluconazole prophylaxis (19.7% vs. 57.1%, P < 0.01). Conclusions We found considerable variability in prescribing practices at our institution, particularly among high-risk patients. In addition, patients who received fluconazole prophylaxis had a statistically significant higher incidence of fungal infections and elevated QTc than those who received other prophylaxis agents and no prophylaxis. Overall, this study highlights the importance of evaluating institutional practices and using guideline-based prophylaxis agents in children at high risk of IFD.

Treatment with tisagenlecleucel (tisa-cel) achieves excellent complete remission rates in children and young adults with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), but approximately 50% maintain long-term remission. Consolidative hematopoietic stem cell transplantation (cHSCT) is a potential strategy to reduce relapse risk, but it carries substantial short- and long-term toxicities. Additionally, several strategies for management of B cell recovery (BCR) and next-generation sequencing (NGS) positivity post-tisa-cel exist, without an accepted standard. We hypothesized that practice preferences surrounding cHSCT, as well as management of BCR and NGS positivity, varies across tisa-cel-prescribing physicians and sought to characterize current practice preferences. A survey focusing on preferences regarding the use of cHSCT, management of BCR, and NGS positivity was distributed to physicians who prescribe tisa-cel for children and young adults with B-ALL. Responses were collected from August 2022 to April 2023. Fifty-nine unique responses were collected across 43 institutions. All respondents prescribed tisa-cel for children and young adults. The clinical focus of respondents was HSCT in 71%, followed by leukemia/lymphoma in 24%. For HSCT-naive patients receiving tisa-cel, 57% of respondents indicated they made individualized decisions for cHSCT based on patient factors, whereas 22% indicated they would avoid cHSCT and 21% indicated they would pursue cHSCT when feasible. Certain factors influenced >50% of respondents towards recommending cHSCT (either an increased likelihood of recommending or always recommending), including preinfusion disease burden >25%, primary refractory B-ALL, M3 bone marrow following reinduction for relapse, KMT2A-rearranged B-ALL, history of blinatumomab nonresponse, and HSCT-naive status. Most respondents indicated they would pursue HSCT for HSCT-naive, total body irradiation (TBI) recipients with BCR before 6 months post-tisa-cel or with NGS positivity at 1 or 3 months post-tisa-cel, although there was variability in responses regarding whether to proceed to HSCT directly or provide intervening therapy prior to HSCT. Fewer respondents recommended HSCT for BCR or NGS positivity in patients with a history of HSCT, in noncandidates for TBI, and in patients with trisomy 21. The results of this survey indicate there exists significant practice variability regarding the use of cHSCT, as well as interventions for post-tisa-cel BCR or NGS positivity. These results highlight areas in which ongoing clinical trials could inform more standardized practice.

Topic Significance & Study Purpose/Background/RationaleHematopoietic cellular therapy (HCT) has become the definitive therapy for several malignant and non-malignant childhood illnesses. As supportive care has evolved, infection remains a primary cause of both morbidity and mortality following HCT. Fever in the immunocompromised patient is an early sign of sepsis. Initiating broad spectrum antibiotics within 60 minutes of initial fever reduces both the morbidity and mortality in immunocompromised patients.ObjectiveReduction in time to antibiotic administration with initial temperature spike above 37.9 C in HCT recipients at Arkansas Children's Hospital.Methods, Intervention, & AnalysisRetrospective data review and education of staff on interventions required when immunocompromised patients develop an initial fever.Findings & InterpretationA retrospective review of 8 patients over 10 months revealed that the time from initial fever to initial antibiotic administration in the post-HCT population at Arkansas Children's Hospital was 91 minutes. Staff education to improve timeliness of antibiotic administration were initiated in August 2021. A checklist was created by the HCT team for nursing staff outlining the steps needed to administer antibiotics properly and efficiently within a 60-minute time limit. The goal was to standardize the process and prioritize the interventions. The checklist was presented to the staff at Education Rounds. Detailed emails discussing the workflow were sent to all hematology/oncology nursing staff. Timers were provided for staff to use to count down from 60 minutes and laminated copies of the checklist were placed at all computer bays in the unit. The checklist and protocol were placed in the new nursing orientation binders and became a mandatory topic in the yearly hematology/oncology nursing education. In December of 2022, data was reviewed of 23 patients over 16 months and revealed a 45% decrease, from an average of 91 minutes to an average of 50 minutes from initial fever to initial antibiotic administration in HCT recipients.Discussion & ImplicationsThe implementation of these interventions improved timely antibiotic administration after initial fever in HCT recipients at Arkansas Children's Hospital. The staff found the check list and timers to be helpful, as well as continued yearly education. Staff did encounter barriers to initiating timeliness of initial antibiotic administration, including physicians’ timeliness in ordering antibiotics and the pharmacy's timely delivery of the antibiotics. Future studies could include the use of conditional antibiotic orders and/or pre-stocked antibiotics on the HCT unit.

IntroductionDiffuse Large B-cell Lymphoma (DLBCL) type post-transplant lymphoproliferative disorder (PTLD) is a common complication in patients receiving immune suppression post solid organ or bone marrow transplant. Treatments for PTLD include: reduction of immunosuppression, CD20 monoclonal antibody therapy, chemotherapy, radiation, or a combination of modalities. Tisagenlecleucel (a CD-19 directed chimeric antigen receptor T-cell) is approved for treatment of refractory DLBCL, but is rarely used as treatment for PTLD.ObjectiveDescribe an experience of tisagenlecleucel use for refractory DLBCL post orthotopic heart transplantMethodsCase descriptionResultsA 20-year-old male with a history of orthotopic heart transplant developed a left cervical mass at 17 years of age. A biopsy revealed DLBCL. Staged rituximab was utilized as initial treatment. Due to refractory disease, he received rituximab, cyclophosphamide, and prednisone. Peripheral blood mononuclear cell harvest was performed and sent for manufacturing. He continued tacrolimus throughout harvest. Harvest procedure was successful with one day of standard MNC collection. Etoposide, doxorubicin, vincristine, prednisone, and cyclophosphamide were given followed by targeted radiation. He underwent surgical resection of the neck mass due to refractory disease. Post-resection PET exhibited refractory disease.During CAR-T therapy, he was admitted to the pediatric intensive care unit for monitoring of heart function due to risk for cytokine release syndrome (CRS) and tumor lysis syndrome. A multidisciplinary team participated in daily rounds. He underwent lymphodepletion with fludarabine and cyclophosphamide before receiving tisagenlecleucel. The patient developed grade 2 CRS on day +1 and Tocilizumab was initiated. He progressed to grade 3 CRS on day +2 and 1 dose of Decadron was given along with vasopressor support. Symptoms improved and Tocilizumab was discontinued on day +3. He was maintained on immunosuppressive therapy with Tacrolimus throughout the admission. The patient discharged on day +10 and had no additional evidence of CRS or ICANS. Day +30 PET scan revealed partial response, and day +77 PET scan exhibited progressive disease. The patient maintains persistent B-cell aplasia.DiscussionTisagenlecleucel is a viable treatment option for treatment of refractory DLBCL in post organ transplant patients with manageable toxicities. Harvest of peripheral blood stem cells is well-tolerated without compromising the transplanted organ. Adverse effects of tisagenlecleucel in a post-heart transplant patient are similar to cancer patients. Optimal patient outcomes may be achieved through multi-disciplinary management. Effectiveness of CAR-T cell therapy for solid tumors continues to be less than ideal, and further research is needed to optimize CAR-T therapy in tumor microenvironments.

Thrombopoietin receptor agonists (TPO-RAs) induce trilineage hematopoiesis under conditions with acquired hematopoietic failure. We evaluated safety, tolerability, and preliminary efficacy of a TPO-RA, romiplostim (Nplate), with or without standard-of-care immunosuppressive therapy (±IST) for children (ages <21 y) with newly diagnosed and relapsed/refractory severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS). Data were collected from an observational study and a single arm interventional pilot study. The safety outcome was treatment-related adverse events (AEs). Efficacy was evaluated by complete hematopoietic response (CHR) at week 24. Romiplostim was commenced at 5 µg/kg/week, with dose escalation of 2.5 µg/kg/week (maximum, 20 µg/kg/dose) based on platelet response. Romiplostim was continued until CHR was observed. Ten subjects (SAA, 9 [IST, 4; without IST, 5]; MDS, 1) completed the study (median age: 9.2 y). Median romiplostim dose was 10 µg/kg/week (range: 5 to 17.5 µg/kg/week). The cumulative incidence of CHR was 70.4% (95% CI, 20.2%-92.6%). Among 21 AEs (Grade 1 to 3), 3 were attributed to romiplostim. At a median posttherapy follow-up of 10.9 months (range: 0.7 to 77.5), no clonal evolution, bone marrow fibrosis or mortality was reported. This proof-of-concept study provides data about short-term safety, tolerability, and preliminary efficacy of romiplostim (±IST) for treatment of pediatric SAA/MDS.

AbstractObjectiveExamine the influence of household income on health‐related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML).DesignSecondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States.ExposureHousehold income was self‐reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity.OutcomeCaregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey.ResultChildren with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2–20.2). Seven percent of enrolled patients presented with high acuity (ICU‐level care in the first 72 h), and 16% had high toxicity (any ICU‐level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction.ConclusionsWhile primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Prompt evaluation and genetic testing of patients who present with recurrent and recalcitrant warts, before onset of severe infection or myelodysplastic syndrome, leads to improved outcomes in patients with GATA2 deficiency.

Background: Black and Hispanic children with acute myeloid leukemia (AML) have consistently demonstrated worse overall survival (OS) compared to non-Hispanic White children. We have previously demonstrated that these children are also less likely to enroll in clinical trials, and that children receiving treatment off-trial experience lower OS. While race/ethnicity are social constructs, some have debated that differential biology may drive some of the survival disparities due to race/ethnicity functioning as a poor proxy for genetic ancestry. There is clinical trial data demonstrating differential racial and ethnic distribution of cytomolecular features which play a critical role in pediatric AML prognostication and risk-stratified treatment determination (Conneely, 2021). However, the generalizability to the real-world setting has not been assessed. We evaluated the distribution of cytomolecular features by race/ethnicity and the contribution of these features to OS disparities among trial-enrolled and non-enrolled patients in a large nationally representative real-world pediatric AML cohort. Methods: This interim analysis of a retrospective cohort included all pediatric (age <19 years) patients treated for AML from January 2011 to April 2023 at 10 institutions in the United States. Data were abstracted from the electronic medical record by trained study personnel, including individual cytomolecular reports (FISH, karyotype, targeted sequencing for CEBPA and NPM1). Patients were categorized into 4 cytomolecular risk profiles: 1) only favorable markers; 2) only unfavorable markers; 3) both favorable and unfavorable markers; 4) neutral. Four favorable and 19 unfavorable markers were defined according to the Children's Oncology Group's most recent classification in AAML1831. Kaplan-Meier survival curves were generated for OS and event-free survival (EFS) by cytomolecular risk profiles. Adjusted Cox models compared the hazard of death and relapse/refractory disease by cytomolecular markers. The frequency of favorable and unfavorable markers was compared by trial enrollment status and race/ethnicity. Results: A total of 654 pediatric patients with AML (54% non-White and non-Hispanic, 39% trial-enrolled) were included in the analytic cohort. Hispanic and non-Hispanic Black (p<0.01) patients were significantly less likely to be enrolled on a clinical trial. Regarding cytomolecular features overall, 27% had only favorable markers, 5% had both favorable and unfavorable markers, 42% had neutral markers, and 26% had only unfavorable markers. Compared to patients with only favorable markers (3-year OS 88.31%; 95% CI: 81.93%-92.54%), patients with both favorable and unfavorable (hazards ratio [HR] = 2.44, p=0.04), neutral (HR=3.64, p<0.001), and only unfavorable (HR=5.47, p<0.001) markers all had increased hazards of death. The hazards for relapse and/or refractory disease were similarly increased (HR=1.92, p=0.03; HR=2.38, p<0.001; HR=3.04, p<0.001, respectively). A test for trend indicated a significant association between cytomolecular risk profile and OS (p<0.001) and EFS (p<0.001). There was no significant difference in cytomolecular risk profiles or individual markers by trial enrollment status. Despite observed trial enrollment disparities, there was also no statistically significant difference in cytomolecular features by race/ethnicity. There was a trend towards Hispanic and non-Hispanic Black patients being more likely to have only favorable cytomolecular compared to non-Hispanic White patients (30.6% and 33.0% vs. 24.5%, p=0.10). Discussion: OS and EFS differed by cytomolecular risk profiles. Black and Hispanic patients were less likely to enroll on clinical trials as previously observed. However, distributions of cytomolecular features were comparable for patients not enrolled on a clinical trial and those enrolled, as well as by race/ethnicity. Thus, differential disease biology does not seem to be the major driver of previously observed survival differences by trial enrollment or race/ethnicity. The alternative mechanism is that social drivers of health (i.e. structural racism) independently impact intermediates such as minimal residual disease (MRD) through differential health care access, delays to presentation, and timely treatment. This will be a critical focus of our future work.

Introduction: Racial and ethnic disparities in survival outcomes exist in pediatric acute myeloid leukemia (AML), but the role of relapse and its potential contribution to outcome disparities is unknown. We sought to examine differences in relapse-free survival (RFS) and clinical characteristics at the time of relapse by race and ethnicity using a real-world multi-institution cohort of pediatric AML patients. Methods: A retrospective cohort including all pediatric (age <19 years) patients treated for AML from 2011-2019 at 13 institutions in the United States was established and is being actively expanded to include diagnoses through 2023. Data collection was accomplished by detailed chart abstraction performed by trained study personnel. We additionally merged resource utilization data from the Pediatric Health Information System to ascertain patient acuity and cumulative organ toxicity. Analyses were restricted to patients identified in the medical record as Hispanic, non-Hispanic Black (NHB), and non-Hispanic White (NHW) to specifically assess historically marginalized patient populations. Other racial/ethnic groups including multi-racial were excluded due to small numbers. Kaplan-Meier survival curves were generated for RFS by race/ethnicity. Adjusted Cox models compared the hazard of relapse by race/ethnicity. Models adjusted for age at diagnosis, sex, initial risk classification, weight category at diagnosis, and acuity at initial presentation. To assess misspecification of outcome, we performed sensitivity analyses restricted to relapses occurring within 1 year of diagnosis (early RFS). Among the patients who relapsed, descriptive frequencies for clinical and treatment characteristics were reported by race/ethnicity. Results: A total of 437 pediatric patients with AML (28% Hispanic, 18% NHB, median follow-up time 3.0 years) were included in the analytic cohort. There were no statistically significant differences in RFS or early RFS by race/ethnicity (Figure 1). However, among relapsed patients, important qualitative differences were noted at the time of relapse (Table 1). Hispanic and NHB patients were older at relapse than NHW patients. Greater proportions of Hispanic and NHB patients (compared to NHW) experienced cardiovascular, respiratory, and renal failure during frontline therapy. Cumulative prevalence of organ failure in 2 or more systems since initial diagnosis was higher for both Hispanic (50%) and NHB (50%) patients compared to NHW patients (29%). Overweight/obesity at relapse was more prevalent among Hispanic (41%) and NHB (50%) compared to NHW (21%) patients. NHB patients were also more likely to present at relapse with higher acuity, defined as requiring ICU-level resources for 2 or more organ systems within 72 hours of admission, compared to NHW patients (75% vs. 57%). Conclusions: Our data suggest a similar risk of relapse by race and ethnicity. However, differences in cumulative frontline organ toxicity and acuity of presentation may lead to differential treatment at the time of relapse and drive subsequent overall survival disparities for Hispanic and NHB patients with pediatric AML. Future Directions: This was a planned interim analysis, and chart abstraction is ongoing to expand this cohort (anticipated N ~1000). We intend to pursue a series of formal mediation analyses regarding the role of relapse, cumulative organ toxicity during frontline treatment, and selection of salvage regimen on disparities in survival outcomes with the expanded cohort.

Autologous hematopoietic cell transplantation (AHCT) remains a standard therapeutic option for patients with multiple myeloma (MM). Outcomes have improved for this patient group after first AHCT, with the use of novel agents in induction, as well as post-transplantation maintenance. High-dose melphalan remains the gold standard as the conditioning regimen for MM. Traditional melphalan is a lyophilized formulation that after reconstitution has insufficient chemical stability and water solubility, thus requiring the addition of propylene glycol to act as a cosolvent to improve these characteristics. After the reconstitution of melphalan with propylene glycol–containing solution, impurities can develop within 30 minutes, and if further dilution occurs, the potency of melphalan diminishes. Propylene glycol is associated with a spectrum of toxicities that can be dose limiting. Evomela is a propylene glycol-free melphalan (PGF-Mel) that at a high dose of 200 mg/2 (100 mg/m2/d for 2 days) is approved for conditioning before AHCT in MM patients. Once reconstituted by directly dissolving in saline solution, PGF-Mel solution can be stored in the vial for up to 1 hour at room temperature or for up to 24 hours at refrigerated temperature (2° to 8°C) with no significant degradation. The demonstrated stability, up to 24 hours at room temperature, results in reduced handling requirements and increased convenience and flexibility of administration. Since its approval, Evomela has been the subject of several retrospective and investigator-initiated studies. This review summarizes the prospective and real-world evidence on practical aspects of PGF-Mel and critically appraises the available data and its clinical implications.

Introduction: Intensive frontline chemotherapy achieves initial remission rates above 80% in pediatric acute myeloid leukemia (AML), however, approximately half of patients relapse, and overall survival (OS) after relapse is poor. There is a paucity of comparative effectiveness data on salvage regimens to inform selection of optimal post-relapse therapy. The objective of this analysis was to compare outcomes following relapse by prevalent reinduction regimens in a multi-center real-world dataset. Methods: Patients 18 years and younger who had received frontline chemotherapy for AML between 2011-2019 at 12 pediatric institutions were eligible for inclusion. Trained personnel completed manual chart abstraction to obtain demographics, diagnosis, treatment, and outcome information. The analysis included patients who achieved morphologic remission and then experienced disease relapse; patients with primary refractory AML and those who pursued palliative therapy only after relapse were excluded. Prevalent reinduction regimens were classified as (1) intensive without anthracycline [e.g. fludarabine/cytarabine and high-dose cytarabine-containing regimens], (2) intensive with anthracycline (e.g. CPX-351, mitoxantrone/cytarabine and cytarabine/daunorubicin/etoposide), and (3) non-intensive (including azacytidine or decitabine-based regimens). Primary outcomes were OS after relapse and end reinduction disease response defined by morphologic remission (<5% blasts) and measurable residual disease (MRD)-negative remission (<0.1% blasts). Covariate distributions were compared by reinduction regimen using chi-square tests. Survival analyses used Kaplan-Meier methods and multivariable cox proportional hazards models. End induction response was evaluated using logistic regression. Adjustment was made for covariates found to both differ by reinduction regimen and be associated with outcome, regardless of statistical significance. Results: Of 530 patients, 157 (29.6%) experienced a relapse at a median of 9.7 months (IQR 6.5-16.3) after initial diagnosis. Median post-relapse follow-up was 2.2 years (IQR 1.1-3.2). One- and 2-year OS rates from relapse were 44.9 ± 4.1% and 38.6 ± 4.1%, respectively. Of 157 patients with relapse, 129 from 9 institutions had available information on post-relapse treatment and pursued reinduction with curative intent. Patients were 48.8% female, 27.1% Hispanic, 14.7% non-Hispanic Black and had a median age of 7.1 years (IQR 2.70-14.2) at relapse. Most patients (89.2%) relapsed after completion of frontline therapy, and 24% had undergone hematopoietic cell transplantation (HCT) in first clinical remission. Reinduction regimens were as follows: 79 (61.2%) received intensive reinduction without anthracycline, 34 (26.4%) received intensive reinduction with anthracycline and 16 (12.4%) received non-intensive reinduction. Patients with a non-intensive reinduction were more likely to have relapsed within one year of initial diagnosis (50% versus 34%, p = 0.23) and undergone transplant prior to relapse (75.0% versus 16.8%, p < 0.001). Covariates were balanced across intensive induction regimens. One-year OS was 50.3 ± 4.6%, with 63 (40.1%) achieving morphologic remission and 40 (31.0%) achieving an MRD-negativity after first reinduction cycle. Seventy-three patients (56.9%) underwent HCT after relapse; 11 (15.1%) received a second transplant. OS curves and adjusted outcome comparisons by reinduction regimen are shown in the Figure and Table. One-year OS was 51.1 ± 5.8%, 60.2 ± 9.0% and 26.7 ± 11.4% for intensive therapy without anthracycline, with anthracycline and non-intensive, respectively. However, after adjustment hazard ratios (HRs) were not statistically significant [HR = 0.85 (p = 0.65) and 1.77 (p = 0.23) for intensive with anthracycline and non-intensive, compared to non-intensive without anthracycline, respectively]. Conclusions: After controlling for patient, disease and treatment characteristics, we did not identify a significant difference in remission rates or OS by reinduction approaches for pediatric relapsed AML. Although anthracycline-based reinduction did not improve OS, adjusted point estimates suggest that anthracyclines may improve end reinduction disease response. Ongoing cohort expansion will enable comparative effectiveness analyses of specific reinduction regimens.

Introduction: Studies have suggested superior outcomes for patients enrolled on clinical trials for their cancer treatment. While sociodemographic disparities in trial enrollment are well established in adults, the literature in children is mixed and limited. A deeper understanding of disparities in pediatric clinical trial enrollment and potential survival differences is critical to ensure the generalizability of trial results and equitable outcomes. In a cohort of children with AML, we sought to examine (1) differences in sociodemographic and clinical characteristics by trial enrollment status, (2) the impact of trial enrollment on survival, and (3) the potential drivers of survival differences. Methods: A retrospective cohort including all pediatric (age <19 years) patients with AML treated at 10 institutions in the United States from 2011-2018 was established and is being actively expanded to include diagnoses through 2023. Chart abstraction by trained study personnel collected detailed demographic and clinical information. Resource utilization data from the Pediatric Health Information System was merged to ascertain patient acuity. Higher acuity was defined as requiring ICU-level resources for 2 or more organ systems within 72 hours of diagnosis. Only patients who had a frontline therapeutic trial option available at their treating institution were included. This was operationalized as a center-level restriction to patients initiating therapy while any frontline trial was enrolling at the center. We additionally included only patients with complete data for all covariates in this analysis. Statistical Analysis: Demographic and clinical characteristics by trial enrollment status were compared using t-test or Fisher's exact test as appropriate. Cox proportional hazards regression estimated hazard ratios (HR) with a doubly robust estimator (adjusted models only) of 4-year OS and EFS by trial enrollment status. A stepwise propensity score (PS) approach assessed the impact of potential drivers of the associations between trial enrollment and overall survival (OS) and event-free survival (EFS). PS were computed by logistic regression and generated stabilized inverse probability weights used for adjustment. First, a Base PS model including a predefined set of potential confounders (age, sex, weight category, preferred language, risk classification, mean annual hospital AML volume) was created. Additional variables of interest were then sequentially added to the PS. The change in adjusted HR relative to the unadjusted comparison was used to quantify the proportion of the association explained at each step. Results: 342 pediatric patients diagnosed with AML with representation from three distinct frontline clinical trials (AAML1031, AML08, and AML16) were included. Patients who were Black (11% vs. 24%), Hispanic (24% vs. 28%), publicly insured (44% vs. 55%), higher acuity (3% vs. 8%), and high-risk classification (29% vs. 34%) were underrepresented in the trial enrollment group compared to non-trial enrolled (Table 1). In unadjusted analyses, trial enrollment was significantly associated with superior OS (HR=0.69, 95% CI 0.47-0.99, p=0.04); there was no significant difference in EFS (HR=0.95, 95% CI 0.69-1.31, p=0.75). Adjustment for the Base PS accounted for 23% of the observed association between trial enrollment and OS (Figure 1). Acuity explained an additional 7% of the association. Inclusion of race/ethnicity and insurance did not result in further adjustment. In fully adjusted analysis, the association was substantially attenuated (HR=0.93, 95% CI 0.59-1.46, p=0.76). Conclusions: Significant sociodemographic and clinical differences exist in frontline trial enrollment for pediatric AML, which may contribute to worse overall survival outcomes for patients not enrolled on trials. Acuity at diagnosis may be a potential modifiable driver of survival differences. These findings support the need to evaluate enrollment patterns across pediatric clinical trials, including how enrollment disparities impact generalizability of clinical trial results, as well as a critical need for interventions designed to improve equity in healthcare access.

antibodies.Anti-N and anti-S antibodies were also obtained.AAR was determined by anti-spike level > 0.5.If patients had positive anti-S response (>0.5), they were considered as previously infected regardless of clinical history. Summary of Results:In patients without prior infection, antibody level analysis post-1 st vaccine showed all 5 of 5 evaluated control patients with AAR. 1 of 7 HM patients and 1 of 2 SM patients developed AAR.Post-2 nd vaccine analysis showed 27 of 28 control patients and 9 of 9 SM patients with AAR.However, only 50% of HM patients had AAR (14 of 27).After 3 rd injection, all control patients (18 of 18) and all SM patients (6 of 6) had AAR, while most HM patients (13 of 14) had AAR.A subgroup analysis of post-2nd vaccine in HM patients found that for non-multiple myeloma malignancies, 5 of 11 patients didn't develop AAR, with 4 having received treatment for underlying malignancy within 3 months.Of the 6 responders, 5 weren't on treatment.In patients with prior infection, post-1 st vaccine analysis showed almost all control patients (9 of 10) and 4 of 5 HM patients developing AAR.No SM patients were collected.After 2 nd vaccine, all 71 control patients, all 20 HM patients, and 11 of 12 SM patients had AAR.Following 3 rd injection, all evaluated patients (33 control, 7 HM, 3 SM) had AAR.Conclusions: Our evaluation showed that HM patients responded differently than the general population or SM patients.In our uninfected cohort, only half of evaluated

Introduction: Since October 2021, there have been two Food and Drug Administration (FDA) approved CD19 CAR-T products (tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel)) for adolescents and young adults (AYA) aged 18 to 25 with B-cell acute lymphoblastic leukemia (B-ALL). Only a small number of AYAs were treated on both registration studies. Comparison across these single arm studies is not possible with differences in demographics and clinical management. We aim to understand prescriber preferences and rationale when deciding between products in the AYA population with B-ALL and inform future clinical investigations. Methods: We conducted a 21-question electronic survey of CAR-T prescribers through the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC). (Note: PTCTC did not formally approve this work but assisted with survey conduct.) The survey consisted of questions about practice demographics and logistics, prescriber opinion and preferences regarding the two FDA approved CAR-T products based on literature data. Results: There was a total of 13 completed surveys from 10 centers at the time of analysis. Most respondents primarily treat patients with hematological malignancies who are 18 years of age or younger (85%). The median FDA approved CAR-T volume among the centers were 1-5 and ranged from 0 to >20. Close to half of respondents (46%) reported their institution requiring committee discussion and approval for all CAR-T cases. Ninety-two percent prescribed tisa-cel for any indication; 23% prescribed brexu-cel for any indication. Within the past year, over half of the respondents treated at least 16 patients with B-ALL (62%) and prescribed at least one CAR-T product. Approximately 31% of the respondents discuss both CAR-T products as treatment options for AYA with B-ALL, and respondents from two centers reported that their center is only certified to prescribe tisa-cel. Since October 2021, 69% of respondents had prescribed tisa-cel for B-ALL while only 15% had prescribed brexu-cel for B-ALL. Regarding current practice, close to half (46%) reported general consensus among their institutional practice is to prescribe tisa-cel for AYA with B-ALL. No one planned to routinely prescribe brexu-cel for AYA with B-ALL, although 31% report planning to consider either CAR-T product on a case-by-case basis. The remaining 23% has no general plan: 15% not having discussed both CAR-T products as an option and 8% is unsure. When asked the clinical data for deciding tisa-cel vs brexu-cel for AYA with B-ALL, some respondents reported more data and experience with tisa-cel, including longer follow-up and better persistence with 4-1BB costimulatory domain. For patients who need CAR-T treatment more urgently, some would consider brexu-cel for the shorter vein to vein time. The respondents were then presented with hypothetical clinical scenarios using published data without revealing the product name and asked to select CAR-T product A (tisa-cel), B (brexu-cel) or if both would be reasonable. When presented with the CR/CRi rate and the 4-1BB vs CD28 co-stimulatory CAR constructs in a blinded fashion, the percent of respondents willing to consider both products as reasonable options were comparable as that reported in practice (close to 31%, with the remaining favoring tisa-cel). However, when presented with reported OS data from both products in blinded fashion, close to 69% of the respondents selected that both products are reasonable options. When presented with product manufacturing turnaround time, 42% of respondents preferred brexu-cel while the remaining 58% respondents felt both products were reasonable. Conclusions: AYA with B-ALL requiring CAR-T therapy are eligible for both tisa-cel and brexu-cel and there exists clinical equipoise as to which product is best for different clinical scenarios given the lack of head-to-head comparison. Most CAR-T prescribers at the time of this survey favored tisa-cel given its availability and familiarity as well as its 4-1BB costimulatory domain. However, some prescribers may favor brexu-cel if there was rapid clinical decline requiring expedited turnaround time. Some changes in product preference when clinical data was presented in a blinded manner were seen, suggesting providers' willingness and feasibility to design a pragmatic study comparing tisa-cel and brexu-cel in real world practice in the AYA population.