Household material hardship and distress among parents of children with advanced cancer: A report from the PediQUEST Response trial.

BACKGROUND: The prevalence and characteristics of household material hardship (HMH) in families of children with advanced cancer and its association with parent distress are unknown and herein described. METHODS: Parents of children aged ≥2 years with advanced cancer at five cancer centers completed baseline surveys as part of the PediQUEST Response trial. HMH (housing, energy, and food) was operationalized as binary (≥1 HMH domains), ordinal (zero, one, or two or more HMH domains), and housing based (none, nonhousing [food and/or energy], only housing, or housing + other). Associations between HMH and parent distress measured by the State-Trait Anxiety Inventory-State and the 10-item Center for Epidemiologic Studies Depression Scale were estimated via linear models adjusting for confounders. RESULTS: Among 150 parents, 41% reported ≥1 HMH (housing, 28% [only housing, 8%; housing + other, 20%]; energy, 19%; food, 27%). HMH was more prevalent among Hispanic, other non-White race, Spanish-speaking, and single parents and those with lower education (associate degree or less) or who were uninsured/Medicaid-only insured. Parents endorsing HMH reported higher anxiety (mean difference [MD], 9.2 [95% CI, 3.7-14.7]) and depression (MD, 4.1 [95% CI, 1.7-6.5]) scores compared to those without HMH. Distress increased with the number of hardships, particularly housing insecurity. Specifically, parents experiencing housing hardship, alone or combined, reported higher distress (housing only: anxiety: MD, 10.2 [95% CI, 1.8-18.5]; depression: MD, 4.9 [95% CI, 1.3-8.6]; housing + other HMH: anxiety: MD, 12.0 [95% CI, 5.2-18.9]; depression: MD, 4.8 [95% CI, 1.8-7.8]). CONCLUSIONS: HMH is highly prevalent in pediatric advanced cancer, especially among historically marginalized families. Future research should investigate whether interventions targeting HMH, particularly housing stabilization efforts, can mitigate parent distress. PLAIN LANGUAGE SUMMARY: In our cohort of parents of children with advanced cancer, household material hardship (HMH) was highly prevalent and significantly associated with higher parent distress. Housing hardship was the primary driver of this association. Families of children with advanced cancer may benefit from systematic HMH screening as well as targeted HMH interventions, especially stabilizing housing.

MRD at the end of induction and EFS in T-cell lymphoblastic lymphoma: Children's Oncology Group trial AALL1231.

ABSTRACT: Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children's Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional bone marrow samples to assess minimal residual disease (MRD) at the end of induction (EOI) were collected in T-LL analyzed to assess the correlation of MRD at the EOI to event-free survival (EFS). Eighty-six (41%) of the 209 patients with T-LL accrued to this trial submitted samples for MRD assessment. Patients with MRD <0.1% (n = 75) at EOI had a superior 4-year EFS vs those with MRD ≥0.1% (n = 11) (89.0% ± 4.4% vs 63.6% ± 17.2%; P = .025). Overall survival did not significantly differ between the 2 groups. Cox regression for EFS using arm A as a reference demonstrated that MRD EOI ≥0.1% was associated with a greater risk of inferior outcome (hazard ratio, 3.73; 95% confidence interval, 1.12-12.40; P = .032), which was independent of treatment arm assignment. Consideration to incorporate MRD at EOI into future trials will help establish its value in defining risk groups. CT# NCT02112916.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

ABSTRACT: Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.

Can extending time between vital sign checks improve sleep in hematopoietic stem cell transplant patients? Testing feasibility, acceptability, and preliminary efficacy.

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) experience barriers to quality sleep. Frequent vital sign checks are necessary early posttransplant given risk of complications but can disrupt sleep. This study tested feasibility and acceptability of extending time between checking vitals (EVs) from every 4 to every 6 h to improve sleep. PROCEDURE: HSCT patients ages 8-21 years (N = 50, mean age = 14.06, SD = 3.58) and their caregivers were enrolled 1-2 days prior to transplant, and 40 patients completed the 15-day study (NCT04106089). Patients wore an actigraph to estimate sleep and provided self- and caregiver-report of sleep. Sleep was observed for nights 0 to +4 posttransplant, and patients were then randomized to EVs either Days +5 to +9 or +10 to +14. Patients were assessed daily for medical eligibility to receive EVs; on days patients were eligible, nightshift nurses (N = 79) reported EV acceptability. RESULTS: Of 200 potential nights for EVs (5 nights x 40 patients), patients were eligible for EVs on 126 nights (63% of eligible nights), and patients received EVs on 116 (92%) of eligible nights. Most patients received EVs ≥3 nights (n = 26, 65%, median = 3 nights). Most patients (85%), caregivers (80%), and nurses (84%) reported that patients used the additional 2 h during EVs for sleep, with reporters indicating moderate to high acceptability. There was preliminary evidence of efficacy indicated by caregiver-reported sleep disturbance and actigraphy-estimated improvements in sleep efficiency during EVs. CONCLUSION: Extending time between vitals checks is highly acceptable to patients, caregivers, and nurses, and may offer a feasible approach to improve sleep in pediatric HSCT.

Disparities in Cytomegalovirus Infection Rates by Race and Ethnicity among Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients at a Single Center.

Previous literature has reported cytomegalovirus (CMV) infection rate disparities among racial/ethnic groups of hematopoietic cell transplantation (HCT) recipients. Because race and ethnicity categorizations are social constructs unlikely to affect biological systems, it is likely there are covariates on the pathway to CMV detection, known as mediators, that can explain the observed disparity. Recent developments in mediation analysis methods enable the analysis of time-to-event outcomes, allowing an investigation of these disparities to also consider the timing of CMV infection detection relative to HCT. This study aimed to explore whether racial and ethnic CMV infection disparities existed within a population of HCT recipients at our center, and whether clinical covariates explained any observed association. The study cohort included all recipients of allogeneic HCT performed at the Children's Hospital of Philadelphia between January 2004 and April 2017 who were CMV PCR-negative pretransplantation, had known donor/recipient CMV serology, and were under blood CMV PCR surveillance. Subjects were followed for 100 days post-HCT. Accelerated failure time models using subject's reported race/ethnicity, dichotomized into non-Hispanic White (NHW) and non-NHW, and exposure and time to CMV detection as outcomes examined whether selected clinical factors-donor/recipient CMV serostatus, recipient age, indication for HCT, hematopoietic cell source, match quality-mediated any identified exposure-outcome association. The analysis included 348 HCTs performed in 335 subjects, with 86 episodes (24.7%) in which CMV was detected via PCR analysis. The accelerated failure time model without mediators estimated that non-NHW subjects had fewer CMV-free survival days (time ratio, .21; 95% confidence interval, .10 to .44). Any hypothesized mediator mediated at most 5% of the total association between race/ethnicity and time to CMV detection. Non-NHW HCT recipients had fewer CMV-free survival days than NHW recipients; none of the clinical factors hypothesized to mediate this association accounted for a significant component of total association. Further research should focus on nonclinical factors influenced by systemic racism to better understand their effect on CMV infection among HCT recipients.

Effect of cytomegalovirus infection on post-transplant hospitalization days among children undergoing allogeneic hematopoietic cell transplantation: A marginal structural model approach.

BACKGROUND: Cytomegalovirus (CMV) commonly reactivates after allogeneic hematopoietic cell transplant (HCT), potentially leading to CMV disease and significant morbidity and mortality. To reduce morbidity and mortality, many centers conduct weekly CMV blood polymerase chain reaction (PCR) surveillance testing with subsequent initiation of antiviral therapy upon CMV DNAemia detection. However, the impact of CMV DNAemia on subsequent hospitalization risk has not been assessed using models accounting for the time-varying nature of the exposure, outcome, and confounders. METHODS: All allogeneic HCTs at the Children's Hospital of Philadelphia from January 2004-April 2017 were considered for inclusion. Patients were monitored with CMV surveillance via PCR testing for up to 105 days after HCT receipt. We estimated the association between CMV DNAemia and rate of hospitalization using marginal structural models (MSM). RESULTS: There were 343 allogeneic HCT episodes in 330 with CMV surveillance; median age was 9.0 (range: 0.1-26.2) and 46.5% were female. And 24.1% of HCT patients had at least one positive CMV blood PCR during the follow-up period. Median time to CMV DNAemia detection was 19 days (range: 4-97). The MSM estimated the incidence rate ratios for an association of CMV DNAemia with hospitalization to be 1.24, (95% confidence interval: 1.04-1.47). CONCLUSIONS: CMV DNAemia was associated with an increased hospitalization in the post-HCT period. The MSM accounted for time-varying nature of the outcome, exposure and confounders. The findings support prevention of CMV DNAemia in this population. We recommend further investigation into the effectiveness and safety of prophylaxis versus pre-emptive CMV prevention approaches.

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation-associated TMA.

ABSTRACT: High-risk, complement mediated, untreated transplant-associated thrombotic microangiopathy (hrTMA) has dismal outcomes due to multi-organ dysfunction syndrome (MODS). The complement C5 blocker eculizumab shows promising results in hrTMA, but has not been prospectively studied in hematopoietic stem cell transplant (HCT) recipients. We performed the first multi-institutional prospective study in children and young adults to evaluate eculizumab as an early targeted intervention for hrTMA/MODS. We hypothesized that eculizumab would more than double survival in HCT recipients with hrTMA, compared to our prior study of prospectively screened, untreated hrTMAs serving as historical controls. HrTMA features (elevated terminal complement (sC5b-9) and proteinuria measured by random urine protein/creatinine ratio (≥1mg/mg)) were required for inclusion. The primary endpoint was survival at 6 six-months from hrTMA diagnosis. Secondary endpoints were cumulative incidence of MODS 6 months after hrTMA diagnosis and 1-year posttransplant survival. Eculizumab dosing included intensive loading, induction, and maintenance phases for up to 24 weeks of therapy. All 21 evaluated study subjects had MODS. Primary and secondary study endpoints were met by demonstrating survival of 71% (P < .0001) 6 months after hrTMA diagnosis and 62% 1 year after transplant. Of fifteen survivors, 11 (73%) fully recovered organ function and are well. Our study demonstrates significant improvement in survival and recovery of organ function in hrTMA using an intensified eculizumab dosing and real time biomarker monitoring. This study serves as a benchmark for planning future studies that should focus on preventative measures or targeted therapy to be initiated prior to organ injury. This trial was registered at www.clinicaltrials.gov as #NCT03518203.

Supportive Care in Pediatric Oncology: Opportunities and Future Directions.

The optimization of outcomes for pediatric cancer patients relies on the successful advancement of supportive care to ease the treatment burden and mitigate the long-term impacts of cancer therapy. Advancing pediatric supportive care requires research prioritization as well as the development and implementation of innovations. Like the prevailing theme throughout pediatric oncology, there is a clear need for personalized or precision approaches that are consistent, evidence-based, and guided by clinical practice guidelines. By incorporating technology and datasets, we can address questions which may not be feasible to explore in clinical trials. Now is the time to listen to patients' voices by using patient-reported outcomes (PROs) to ensure that their contributions and experiences inform clinical care plans. Furthermore, while the extrapolation of knowledge and approaches from adult populations may suffice in the absence of pediatric-specific evidence, there is a critical need to specifically understand and implement elements of general and developmental pediatrics like growth, nutrition, development, and physical activity into care. Increased research funding for pediatric supportive care is critical to address resource availability, equity, and disparities across the globe. Our patients deserve to enjoy healthy, productive lives with optimized and enriched supportive care that spans the spectrum from diagnosis to survivorship.

The spatial and temporal structure of neural activity across the fly brain.

What are the spatial and temporal scales of brainwide neuronal activity? We used swept, confocally-aligned planar excitation (SCAPE) microscopy to image all cells in a large volume of the brain of adult Drosophila with high spatiotemporal resolution while flies engaged in a variety of spontaneous behaviors. This revealed neural representations of behavior on multiple spatial and temporal scales. The activity of most neurons correlated (or anticorrelated) with running and flailing over timescales that ranged from seconds to a minute. Grooming elicited a weaker global response. Significant residual activity not directly correlated with behavior was high dimensional and reflected the activity of small clusters of spatially organized neurons that may correspond to genetically defined cell types. These clusters participate in the global dynamics, indicating that neural activity reflects a combination of local and broadly distributed components. This suggests that microcircuits with highly specified functions are provided with knowledge of the larger context in which they operate.

Hospitalists in Pediatric Oncology/Stem Cell Transplant: Successes and Opportunities.

As hospitalized pediatric patients have grown in number and complexity, and residency structural changes have reduced resident coverage, inpatient care models have changed to include additional providers at the "front line." Hospitalists are increasingly employed in general pediatric units, but in specialized inpatient areas, hospitalist care models are less common. Hospitalist programs in pediatric oncology are few and unique, and thus there are limited data assessing this role. Here we describe the oncology/stem cell transplant hospitalist program at the Children's Hospital of Philadelphia with a survey project to assess the perceptions of physicians in the role. Hospitalists from 2017 to 2019 (n=26) were surveyed to assess nonclinical roles and job satisfaction. With a response rate of 84.6%, all respondents concurred work-life balance, hours, and flexibility are attractive and found the field intellectually stimulating. Most (86.4%) agreed there were significant academic opportunities. The vast majority felt this job was valuable in attaining career and personal goals; 95.5% were happy they accepted this position. As the pediatric oncology/stem cell transplant hospitalist position is a viable, versatile career path providing ample academic opportunities and job satisfaction, the expansion of such a model within our institution and others should be well received.

Quality Improvement Initiative to Improve Time and Adherence to Revaccination after Hematopoietic Cell Transplantation: Implementation of a Revaccination Clinic within the Transplantation Program.

Revaccination after hematopoietic cell transplantation (HCT) is critical to prevent morbidity and mortality from vaccine-preventable illnesses. The global aim of our quality improvement initiative was to enhance timely, correct, and effective revaccination after pediatric HCT. The SMART aim of our project was to decrease median unvaccinated time by 4 months by decreasing the time to vaccine eligibility, time from eligibility to vaccine initiation, and time to completion of the vaccine series. A multidisciplinary group performed a cross-sectional quantitative and qualitative evaluation of revaccination practices at our institution. We identified factors associated with delayed, incorrect, or incomplete revaccination. Several plan-do-study-act interventions were implemented to address these drivers, including revising immune readiness criteria, increasing auditing of primary care administered immunizations, and, importantly, establishing a dedicated revaccination clinic within the HCT clinic at our center. The time to vaccine eligibility decreased from 12.6 months to 10 months (a 20% decrease), and the time to complete the vaccine series decreased from 19.3 months to 15.7 months (a 19% decrease). With a quality improvement initiative, we addressed the many causes of delayed or incomplete revaccination post-HCT and through a team-based approach successfully decreased the time to vaccine start and time to vaccine completion at our center.

A Retrospective Review of Revaccination Patterns in Pediatric Hematopoietic Stem Cell Transplantation Recipients.

Background: After a hematopoietic stem cell transplantation (HSCT), patients are left with little to no immunity to prevent infections. Importantly, this includes immunity gained from previous exposures, including vaccinations. This loss of immunity is a direct result of previous chemotherapy, radiation, and conditioning regimens the patients receive. It is critical to revaccinate patients post-HSCT to ensure protective immunity against vaccine-preventable diseases. Before 2017, all patients at our institution were referred to their pediatrician at approximately 12-month post-HSCT to be revaccinated. Clinical concern was raised at our institution regarding nonadherence and errors in vaccine schedules. Methods: To understand the magnitude of the problem with revaccination, we performed an internal audit of post-vaccine adherence in patients who received an HSCT between 2015 and 2017. A multidisciplinary team was developed to review the audit results and make recommendations. Results: This audit revealed delays in the initiation of the vaccine schedule, incomplete adherence to the recommended revaccination schedule, and errors in administration. Discussion: Based on the review of the data, the multidisciplinary team recommended an approach for systematic assessment of vaccine readiness and centralization of the administration of vaccines to be done within the stem cell transplant outpatient center.

Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma.

PURPOSE: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS (P = .412) and OS (P = .600). CONCLUSION: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.

Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.

Unrelated donor α/ß T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia.

Unrelated donor (URD) hematopoietic stem cell transplant (HSCT) is associated with an increased risk of severe graft-versus-host disease (GVHD). TCRαß/CD19 depletion may reduce this risk, whereas maintaining graft-versus-leukemia. Outcome data with TCRαß/CD19 depletion generally describe haploidentical donors, with relatively few URDs. We hypothesized that TCRαß/CD19-depletion would attenuate the risks of GVHD and relapse for URD HSCT. Sixty pediatric and young adult (YA) patients with hematologic malignancies who lacked a matched-related donor were enrolled at 2 large pediatric transplantation centers between October 2014 and September 2019. All patients with acute leukemia had minimal residual disease testing, and DP typing was available for 77%. All patients received myeloablative total body irradiation- or busulfan-based conditioning with no posttransplant immune suppression. Engraftment occurred in 98%. Four-year overall survival was 69% (95% confidence interval [CI], 52%-81%), and leukemia-free survival was 64% (95% CI, 48%-76%), with no difference between lymphoid and myeloid malignancies (P = .6297 and P = .5441, respectively). One patient (1.7%) experienced primary graft failure. Relapse occurred in 11 patients (3-year cumulative incidence, 21%; 95% CI, 11-34), and 8 patients (cumulative incidence, 15%; 95% CI, 6.7-26) experienced nonrelapse mortality. Grade III to IV acute GVHD was seen in 8 patients (13%), and 14 patients (26%) developed chronic GVHD, of which 6 (11%) had extensive disease. Nonpermissive DP mismatch was associated with higher likelihood of acute GVHD (odds ratio, 16.50; 95% CI, 1.67-163.42; P = .0166) but not with the development of chronic GVHD. URD TCRαß/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02323867.

Improving Guideline-Congruent Care for Chemotherapy-Induced Nausea and Vomiting Prophylaxis in Pediatric Oncology Patients.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a very common side effect of pediatric cancer therapy. High-quality, evidence-based, pediatric-specific guidelines for prophylaxis and treatment of CINV are available. At many centers, guideline-concordant care is uncommon. We formed a multidisciplinary quality improvement team to implement guideline-concordant care for CINV prophylaxis at our center. We present the results following the first year of our interventions. METHODS: We planned and implemented a multipronged approach in three key phases: (1) developing and publishing an acute CINV prophylaxis pathway, (2) education of providers, and (3) updating the computerized provider order entry system. We used iterative, sequential Plan-Do-Study-Act cycles and behavioral economic strategies to improve adherence to guideline-concordant CINV prophylaxis. We focused on aprepitant usage as a key area for improvement. RESULTS: At the beginning of the study period, < 50% of patients were receiving guideline-concordant CINV prophylaxis and < 15% of eligible patients were receiving aprepitant. After 1 year, more than 60% of patients were receiving guideline-concordant care and 50% of eligible patients were receiving aprepitant. CONCLUSION: We describe the development and implementation of a standardized pathway for prevention of acute CINV in pediatric oncology patients. With a multidisciplinary, multifaceted approach, we demonstrate significant improvements to guideline-congruent CINV prophylaxis.

Pulmonary Outcomes After Autologous Stem Cell Transplant for Hodgkin Lymphoma.

Autologous hematopoietic stem cell transplant (ASCT) may be curative therapy for pediatric patients with relapsed/refractory Hodgkin lymphoma (HL). Therapy for HL may involve pulmonary toxic modalities. Little information exists regarding pulmonary function in these patients post-ASCT. A retrospective chart review was performed for patients undergoing ASCT from February 2012 to December 2019. Lung disease was defined as a z -score ≤-1.7 in forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), total lung capacity (TLC), or diffusing capacity of lung for carbon monoxide. Descriptive and limited statistical analyses were performed. Twenty-eight patients were included. Median age at diagnosis was 15 (2 to 19) and was 17 (4 to 21) at ASCT. Twenty-three received radiation before ASCT. Fourteen received brentuximab before, and 9 after, transplant. Nineteen met criteria for lung disease post-ASCT. Sixteen had lung disease before ASCT. Longitudinal trends for pulmonary function testing parameters did not reach statistical significance, however, FEV 1 , FVC, and TLC trended towards worsening immediately post-transplant. There was no statistically significant change in FEV 1 , FVC, or TLC at 2 years as compared with pretransplant data, suggesting no substantial difference from baseline. Diffusing capacity of lung for carbon monoxide showed statistically significant improvement at the 2 year timepoint ( P =0.03). This data reinforces the importance of close follow-up for these patients. Large cohort studies are necessary to identify risk factors so that possible mitigative strategies or alternate regimens could be used.

Incidence of CMV Infection and Disease and Adverse Events Associated with Antiviral Therapy in a Retrospective Cohort of Allogeneic Hematopoietic Cell Transplant Recipients at an Academic Children's Hospital.

BACKGROUND: Cytomegalovirus (CMV) is a significant source of morbidity and mortality among transplant recipients; the epidemiology is less understood in pediatric hematopoietic cell transplantation (HCT) cohorts. Furthermore, there is a paucity of data related to CMV prophylactic and preemptive strategies. METHODS: A single-center retrospective observational cohort of allogeneic HCT recipients at the Children's Hospital of Philadelphia January 1, 2004-December 31, 2017 was constructed. Subjects were followed for 180 days after transplant to determine whether they had CMV infection or disease. Data on antiviral therapy were collected as were outcomes of CMV disease and adverse events (AEs) related to the antiviral therapy. RESULTS: Between January 2004 and March 2017, 345 allogeneic HCTs in 333 patients undergoing CMV surveillance testing were identified. CMV DNAemia was detected during the 180-day follow-up in 89 (25.8%) HCTs. CMV recipient-positive transplants were most likely to have CMV infection (47%). Infection rates were high for those receiving a CMV-specific prophylaxis regimen (50%). CMV DNAemia progressed to CMV disease 11.2% of the time. Of 224 subjects receiving CMV-specific prophylaxis, 19.2% experienced ≥1 AE. Of 53 receiving preemptive therapy during any CMV DNAemia episode, 32.1% experienced ≥1 AE. CONCLUSIONS: CMV infection is common in pediatric allogeneic HCT recipients. The CMV-specific prophylaxis regimen employed in this cohort did not effectively prevent DNAemia, progression to CMV disease was uncommon, and AEs from prophylaxis and preemptive therapy were frequent. Novel approaches that reduce the impact of CMV on pediatric allogeneic HCT recipients are needed.