BACKGROUND:The utility of chemotherapy for childhood ependymoma is uncertain without a prior randomized trial. METHODS:ACNS0831, a multicenter phase 3 randomized study conducted through the Children's Oncology Group (COG), included patients 1-21 years with newly diagnosed intracranial ependymoma. Patients with complete/near-total resections (GTR/NTR) or complete response (CR) to induction therapy were randomized to radiation (RT) alone or RT followed by chemotherapy (RT-CHEMO). Primary outcomes were event-free survival (EFS) and overall survival (OS). Due to anticipated noncompliance with chemotherapy, an "as treated" analysis was planned. Patients with subtotal resection (STR) were non-randomly assigned to RT-CHEMO. Grade 2 supratentorial tumors with GTR or CR to induction therapy were observed. RESULTS:Of 449 eligible patients, 325 with GTR/NTR or CR were randomized. Five-year EFS was 63.7% (95% CI: 55.1%-71.1%) for RT only (n = 161) versus 69.2% (60.8%-76.3%) for RT-CHEMO (n = 164) (1-sided log-rank P = .299, HR = 0.866). Five-year OS was 86.9% (79.8%-91.6%) for RT only versus 88.3% (81.8%-92.6%) for RT-CHEMO (1-sided log-rank P-value = .172, HR = 0.757). The "as treated" and "as randomized" analysis results were similar. Sixty-three subjects with STR were assigned to RT-CHEMO; 5-year EFS was 33.6% (22.1%-45.5%) and OS 74.0% (60.5%-83.5%). Supratentorial grade 2 tumors with GTR or CR were observed with a 5-year EFS of 66.9% (49.0%-79.7%) and OS of 100%. Molecular classification was provided for 94% (n = 422) of all subjects. CONCLUSIONS:Primary analysis showed no benefit for maintenance chemotherapy. Further follow-up is important to assess its effect on late relapses. This is the largest cohort of molecularly classified ependymomas treated on a Phase 3 randomized trial.

BACKGROUND:Proton beam radiotherapy (PBRT) is a mainstay in treatment of pediatric brain tumors and may reduce risk of neurotoxicity. We hypothesized that dose-dependent effects on resting-state networks (RSNs) would manifest as impaired neurocognition and quality of life (QoL) in pediatric patients undergoing PBRT. METHODS:Patients and age- and sex-matched healthy controls (HCs) were prospectively enrolled and underwent resting-state functional connectivity (FC) MRI and neurocognitive tests (NIH Toolbox, PROMIS QoL Questionnaire) at 3-5 months post-PBRT. Functional connectivity within and between RSNs (default mode network [DMN], dorsal attention network [DAN], executive central network [ECN], salience network [SN]) was compared. One-sample t-tests assessed average RSN-specific FC. Group-level analysis used paired t-tests (q = 0.05). RESULTS:Twenty-eight participants (14 patients, 14 HCs; median age 14 years) were analyzed. Compared to HCs, patients displayed worse attention/executive function (P = .018), working memory (P = .011), and processing speed (P = .047). Patients had lower within-network FC in DMN (P = .013) and SN (P = .026). Patients had disrupted anticorrelation between DMN and SN, and less local efficiency of RSNs (corrected P < .05). Higher brain volume receiving ≥20 Gy, left hippocampus mean dose, and left temporal lobe mean dose were associated with RSN disruption in DMN and SN (|r|≥0.70). Lower SN FC was associated with poorer processing speed (P = .049). On multivariable analysis, ECN FC was associated with working memory (P = .016) and patients had worse working memory vs HCs (P = .009). CONCLUSIONS:Compared to HCs, pediatric patients after PBRT displayed significant disruption in several RSNs, notably between SN and DMN critical in neurocognitive control. Dose-dependent neurocognition and QoL impairment warrant further investigation for mitigation.

BACKGROUND:Children treated for acute lymphoblastic leukemia (ALL) are at risk of neurocognitive deficits in attention-concentration, working memory, executive function, and psychomotor speed. OBJECTIVES:This study evaluated longitudinal trajectories and medical/demographic associations with neurocognitive outcomes during treatment of newly diagnosed ALL. METHODS:Patients ages 3-21 treated on DFCI 16-001 (NCT03020030) across eight North American sites (2017-2022) were evaluated using Cogstate across four timepoints from diagnosis through maintenance phase. Linear mixed models estimated trajectories and interactions with clinical factors over time, incorporating random effects for patients and sites. RESULTS:Among 298 patients (median age 7.9 years, 53% male), performance changed significantly over time in varying directions for executive functioning, attention, visual learning, and working memory-accuracy (all p < 0.001). There was a significant interaction overall between age and time for psychomotor function (interaction p = 0.01) and working memory-accuracy (interaction p < 0.001). Older age was associated with worse performance on working memory-speed (β = -0.04) and attention (β = -0.05). Female sex was associated with worse performance on psychomotor function (β = -0.27) and working memory-accuracy (β = -0.50), but better on visual learning (β = 0.47) and working memory-speed (β = 0.30). A greater-than-expected proportion of participants performed below -1.5 SD on tests of attention, executive functioning, and psychomotor functioning at multiple timepoints. CONCLUSIONS:While most patients demonstrated normal neurocognitive functioning, including variable trajectories, a subgroup performed poorly on attention, executive functioning, and psychomotor functioning. Risk factors include older age at diagnosis and female sex, which may provide insight into groups warranting early intervention.

BACKGROUND:Sickle cell disease (SCD) is a chronic and life-limiting hemoglobin and systemic vascular disease. While over 1000 people have undergone hematopoietic cell transplantation (HCT) over the last 40 years, long-term disease-specific and health-related quality of life data are lacking. The American Society of Hematology 2021 Guidelines for SCD emphasized the need for more detailed registry data to inform patients and providers with decision-making and practice recommendations. PROCEDURES:In January 2021, the Sickle Cell Transplant Advocacy and Research Alliance (STAR) launched Project Sickle Cure (PSC). This multi-center, prospective study of patients who have undergone HCT for SCD includes baseline demographics and SCD-specific post-HCT outcomes, serial neurocognitive testing, health-related quality of life measures, health equity evaluations, a neuroimaging bank, detailed evaluation of neurologic status pre- and post-transplant, and chronic pain evaluation. A biorepository is in the planning stage of development. RESULTS:As of November 2025, 115 participants have enrolled at 18 STAR sites with enrollment ongoing. CONCLUSIONS:PSC is a STAR prospective study which will address a major gap in our understanding of outcomes post-HCT specific to SCD. WeDecide, a larger study comparing HCT health-related quality of life outcomes to those who receive non-transplant disease modifying therapy (NT-DMT) is in development, and PSC will provide the HCT comparator data. These data will also be highly relevant as other curative and transformative therapies, such as gene therapy, become more widely used.

BACKGROUND:Survivors of childhood acute lymphoblastic leukemia (ALL) frequently exhibit treatment-related neurocognitive impairment, although there is substantial interpatient variability in this outcome. Analysis of biomarkers that reflect the impact of chemotherapy during the two years of treatment for ALL offers the potential to identify children who have subclinical treatment-related neurotoxicity at a time when a protective intervention could prevent the development of persistent impairment. METHODS:We prospectively measured markers indicative of oxidative stress (8-hydroxydeoxyguanosine) and neurodegeneration (total tau) in cerebrospinal fluid (CSF) collected at five timepoints before and during the first year of chemotherapy for ALL among 529 patients enrolled on Dana-Farber Cancer Institute ALL Consortium protocol 16-001 (NCT03020030). RESULTS:CSF 8-hydroxydeoxyguanosine and total tau change significantly over time, with parallel increases emerging during intensive phases of therapy, especially following repeated doses of intrathecal chemotherapy. A concordant increase in both markers was observed in 50% of patients; a concordant decrease was seen in a smaller subset (15%). In multivariable analysis, higher CSF tau was significantly associated with White race and non-Hispanic ethnicity. CONCLUSIONS:Analysis of CSF collected prospectively in a large cohort of children treated for ALL demonstrated significant changes in markers of oxidative stress and neurodegeneration within three months of treatment initiation. IMPACT:The clinical relevance of the putative biomarkers reported here will be validated by testing whether they are predictive of treatment-related cognitive decline. These biomarkers may then serve as surrogate markers for testing the efficacy of protective interventions designed to protect against treatment-induced neurotoxicity and cognitive decline.

Although typically curative, treatment for pediatric acute lymphoblastic leukemia (ALL) is associated with neurotoxicity and leads to chemotherapy-related cognitive impairment (CRCI) in 40–70

Abstract Hematopoietic cell transplantation (HCT) for pediatric sickle cell disease (SCD) has steadily increased, however data on long-term effects is limited. Previous registry studies focused on survival, rejection and GVHD. Data on long-term health-related quality of life (HRQoL) post-HCT in SCD is limited by small sample sizes and short follow-up. The objective of Project Sickle Cure (PSC) is to measure HRQoL and decisional regret (DR) in children with SCD, hypothesizing that HCT will improve HRQoL longitudinally with low rates of DR. PSC is a prospective observational multicenter study of SCD participants undergoing allogeneic HCT. Since 2021, 15 STAR sites in North America have enrolled 89 participants, with 65 having >6 mo post-HCT follow-up and included in this analysis. Baseline demographics, disease, and HCT characteristics were collected and summarized. Participants and their primary caregivers complete HRQoL measures (PedsQL Generic Core [GC], PedsQL Family Impact Module [FIM], and Patient Reported Outcomes Measurement Information System [PROMIS]) measures alongside a new DR Scale (DRS; higher scores indicate greater regret). Data are collected pre-HCT and post-HCT at 30, 90, and 180 days (d) and 1, 2, and 3 years (yrs). General linear mixed-effects models were used to evaluate preliminary changes over time. Results are presented as least-square means (LSM) and differences in least-square means (ΔLSM) from baseline. In this interim exploratory analysis, no statistical adjustments to p-values (e.g., alpha spending or corrections for multiple testing) were applied; results may differ after full enrollment and completion of planned analyses. Mean duration of follow up was 2.3 yrs (SD=1.0), with 85% >1 yr post-HCT. Participants were 46% male with mean age at HCT of 10.1 yrs (SD=5.3). Most had HbSS genotype (94%), and disease severity was severe, less severe, and mild in 35%, 35%, and 30%, respectively. Donor was matched related in 75%, bone marrow graft source in 68%, and conditioning was myeloablative in 53%, reduced intensity in 38%, and nonmyeloablative in 9%. Acute GVHD of any severity was reported in 34%, and any chronic GVHD in 5%. Many participantshad significant improvement from baseline in multiple domains of HRQoL, some with sustained improvement and from the earliest timepoint. For PedsQL GC, patient (pt) and parent-proxy HRQoL significantly increased from LSM=71.7 and 73.7 at baseline starting d 180 and 1 yr to 78.3 and 81.2 by yr 2, respectively (pt ΔLSM (95% CI)=6.6 (0.6,12.6), p=.032; parent-proxy ΔLSM (95% CI)=7.5 (0.1,14.9), p=.046). For PedsQL FIM, parent-reported total family functioning significantly increased from baseline of LSM=76.3 to 88.3 starting d 180 to yr 3 (ΔLSM (95% CI)=12.1 (2.9, 21.2), p=.011). Patient PROMIS scores significantly improved from baseline for anxiety (starting d 30) and fatigue up to yr 1 (anxiety ΔLSM (95% CI) =-6.0 (-10.5,-1.5), p=.009; fatigue ΔLSM (95% CI)=-6.8 (-12.4,-1.2), p=.019), as well as mobility from yr 2 to yr 3 (ΔLSM (95% CI)=7.2 (0.3,14.1), p=.040) and pain interference from yr 1 up to yr 2 (ΔLSM (95% CI)=-7.9 (-14.8, -1.0), p=.024). Parent-proxy scores significantly improved from baseline up to yr 3 for anxiety (from d 180; ΔLSM (95% CI)=-8.6 (-15.4,-1.8), p=.013), fatigue (from 1 yr; ΔLSM (95% CI)=-9.2 (-16.1,-2.3), p=.009), mobility (from yr 2; ΔLSM (95% CI)=6.6 (1.3,12.0), p=.016), and pain interference (from d 90; ΔLSM (95% CI)=-11.0 (-17.8,-4.2), p=.002). Pt and parent-proxy depression did not significantly differ from baseline. Though pt peer relationship scores significantly decreased from baseline to d 180 (ΔLSM (95% CI)=-4.8 (-9.1,-0.4),p=.031), all scores remained above cut-off for impairment. For DRS, pt and parent-proxy scores indicated low regret up to yr 3 (LSM=17.5 and 11.2, respectively), which did not significantly differ from baseline at d 90. Most PROMIS HRQoL scores were normal pre-HCT in our cohort. Previous studies with smaller sample sizes have demonstrated both low and high baseline scores. However, it is the favourable change from baseline which is of greater relevance to patients and providers. In conclusion, our interim analysis demonstrated significant improvements in multiple domains of HRQoL at longitudinal timepoints, as early as 30 d and lasting up to 3 yrs post-HCT with low DR. Our findings are strengthened by our large cohort, duration of follow-up and the use of diverse measures, including a novel DRS.

BACKGROUND:This study describes neurocognitive functioning during the first month of induction chemotherapy for childhood acute lymphoblastic leukemia (ALL) and associations with age, sex, risk of relapse, maternal education, household material hardship (HMH), and oxidative stress. METHODS:Patients treated on protocol 16-001 (NCT03020030) across eight North American sites (2017-2022) consented for optional testing using Cogstate at six timepoints throughout treatment. The baseline data presented were collected within the first month after diagnosis. RESULTS:Among 406 eligible patients, 330 (81%) consented (53% males, mean age = 8.8 years, SD = 4.7). Over 63% of participants performed within normal limits for their age range. Additionally, no relationship was observed at baseline between neurocognition and maternal education, HMH, or oxidative stress. In contrast, a linear relationship was observed between older age and weaker psychomotor speed (p < 0.0001), attention (p < 0.0001), and working memory (p = 0.019). Males also demonstrated faster psychomotor speed (p = 0.0027), while females demonstrated stronger visual learning (p = 0.011). Furthermore, having a higher risk of relapse was associated with slower psychomotor speed (p = 0.006) and weaker attention (p = 0.033). CONCLUSIONS:Our findings indicate that most ALL patients in this study who were assessed at baseline did not display cognitive impairments, except for a small subset of participants who were below age expectations across domains. These baseline findings also identify subgroups based upon age, sex, and ALL risk classification that begin medical treatment with neurocognitive delays, warranting monitoring to elucidate whether exposure to therapy further impacts these domains. Additionally, the lack of impact on neurocognitive functioning at baseline of maternal education, HMH, and/or oxidative stress enables subsequent assessments to effectively identify the potential emergence of deficits as a result of exposure to medical treatment.

Pediatric cancer survivors may face elevated risk for developing diabetes mellitus, which may independently contribute to long‐term neurocognitive impairments outside of the effects of cranial irradiation. Webster et al. (2025) provide initial findings regarding this association using self‐report data from the Childhood Cancer Survivorship Study, emphasizing the need for future research to explore underlying mechanisms, bolster findings with performance‐based assessment methods, and develop targeted interventions for this vulnerable population.

BACKGROUND:The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown. METHODS:We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions. RESULTS:Twelve of 16 patients (n = 75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n = 3), intraventricular radioimmunotherapy (n = 3), or both CSI and intraventricular radioimmunotherapy (n = 1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5 years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5 years. CONCLUSIONS:CSI (23.4 Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB.

BACKGROUND:Late morbidity after childhood cancer may be mitigated by healthy lifestyle behaviors. We piloted a game-based, parent-child digital intervention to increase activity in sedentary survivors. METHODS:Survivors aged 10-16 treated with cardiotoxic therapy and not meeting US physical activity guidelines were enrolled in a single-arm study with a parent. Following a 14-day run-in, participants chose a prespecified step goal and wore an accelerometer daily for 24 weeks (12-week game-based intervention; 12-week follow-up). Participants completed the Acceptability of Intervention Measure (AIM) at 24 weeks; a subset of dyads completed qualitative interviews. RESULTS:Among 129 eligible survivors, 27 enrolled (20.9% participation rate) with a parent. Four dyads were removed during the 14-day run-in period due to noncompliance. Among the 23 dyads who continued to the study, the tracker was worn for 95% of days during the 12-week intervention (95% confidence interval [CI]: 94-96) and 81% during the 12-week follow-up (95% CI: 79-82). Overall, the prespecified step goal was met for 64% (95% CI: 63-66) of days during the intervention and 37% (95% CI: 35-38) during the follow-up. At the end of study, 17/23 dyads responded to AIM; 82% of survivors and 94% of parents reported the intervention as acceptable. During qualitative interviews (n = 5), dyads noted that they liked the accountability of the "buddy system," but would have liked more personalized goal-setting. CONCLUSIONS:Despite high ratings of acceptability among participants, difficulties with sustained adherence and retention were encountered in this parent-child gamification intervention. Alternate, tailored designs should be considered in the future.

Treatment of acute lymphoblastic leukemia (ALL) is associated with neurocognitive deficits in young children. While computerized measures have been utilized in pediatric oncology research, they exclude patients below the age of 4 years. Patients enrolled on "Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents" were offered participation in an optional neurocognitive study. Three-year old patients did not differ from 4-year-old patients in their ability to perform or complete the tests. Including patients diagnosed at age 3 will serve to improve our understanding of at-risk patients and their neurocognitive trajectory both during and after treatment.

Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions.This study collects CSF while prospectively assessing neurocognitive functioning (working memory, executive function, learning, processing speed, and attention) of ALL patients using the Cogstate computerized battery at six time points during and after the 2 years of leukemia treatment on a Dana-Farber Cancer Institute ALL Consortium trial.Baseline data collected during the first 3 weeks of induction chemotherapy indicate reliable data as all subjects (N = 34) completed Cogstate baseline testing, while completion and performance checks indicate that 100 % of subjects completed testing and complied with test requirements. The majority (85 %) exhibited normal function compared with age peers. Preliminary analysis of CSF biomarkers (folate, homocysteine, 8-isoprostane, and myelin basic protein) similarly reveals values at baseline within expected normal ranges.The first month of induction therapy for ALL is a reliable baseline for detecting treatment-induced changes in neurocognitive functioning. Consequently, serial data collection might identify subgroups of ALL patients at increased risk for neurocognitive decline, warranting proactive interventions to improve their level of functioning both during treatment and into survivorship.

Background Executive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations. Methods Sixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning. Results There were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups. Conclusions Parents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.

Background Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. Procedure Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. Results MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. Conclusion The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.

Primary brain tumors are the most commonly diagnosed solid tumors in children, and pediatric brain tumor survivors experience lasting, pervasive deficits of neurocognitive functioning. Repeated exposure to anesthetic drugs is a necessary component not only of surgical resection but also of multimodal cancer care for the youngest patients with brain tumors. The potential for anesthetic neurotoxicity to worsen neurocognitive outcomes in this vulnerable group, therefore, warrants our attention and further study through multi-disciplinary collaboration. This review discusses neurocognitive functioning in pediatric brain tumor survivors, highlighting the findings of a recent study of children with tumors of the posterior fossa which identified treatment-related risk factors for neurocognitive difficulties, with those undergoing multimodal therapies (eg, chemotherapy and irradiation) experiencing the greatest deficits compared with healthy controls. The role of anesthetic neurotoxicity in long-term outcomes among pediatric brain tumor survivors is also reviewed.

The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported. In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children’s Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.