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A regimen substituting brentuximab vedotin for bleomycin improved 3-year event-free survival among children and adolescents with Hodgkin’s lymphoma by nearly 10 percentage points without a major increase in toxic effects.

Allogeneic hematopoietic cell transplantation (alloHCT) is a highly specialized procedure. We surveyed adult transplant centers in the United States (US) and then used data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008–2010) to evaluate associations of center volume, infrastructure, and care delivery models with survival post alloHCT. Based on their 2010 alloHCT volume, centers were categorized as low-volume (≤40 alloHCTs; N = 42 centers, 1900 recipients) or high-volume (>40 alloHCTs; N = 41 centers, 9637 recipients). 100-day survival was 86% (95% CI, 85–87%) in high-volume compared with 83% (95% CI, 81–85%) in low-volume centers (difference 3%; P < 0.001). One-year survival was 62% (95% CI, 61–63%) and 56% (95% CI, 54–58%), respectively (difference 6%; P < 0.001). Logistic regression analyses adjusted for patient and center characteristics; alloHCT at high-volume centers (odds ratio [OR] 1.32; P < 0.001) and presence of a survivorship program dedicated to HCT recipients (OR 1.23; P = 0.009) were associated with favorable 1-year survival compared to low-volume centers. Similar findings were observed in a CIBMTR validation cohort (2012–2014); high-volume centers had better 1-year survival (OR 1.24, P < 0.001). Among US adult transplant centers, alloHCT at high-volume centers and at centers with survivorship programs is associated with higher 1-year survival.

Objectives/Goals: Our aim is to compare scores collected from a health utilities measure (Health Utility Index, HUI) to those collected from a profile measure (Child Health Ratings Inventories, CHRIs- Global) among youth with newly diagnosed, high-risk classic Hodgkin lymphoma. Methods/Study Population: We will analyze existing data collected during the Children’s Oncology Group AHOD 1331 trial, which was a phase 3 clinical trial comparing the efficacy of adding brentuximab vedotin to standard-of-care treatment with multiagent chemotherapy in children and adolescents with high-risk Hodgkin lymphoma. The study also had a prespecified patient-reported outcomes (PRO) secondary aim, which involved recruiting a subset of the initial 309 patients aged 11 years or older enrolled in the trial for serial PRO measures taken over the trial period. Health-related quality of life (HRQoL) was assessed by CHRIs, HUI version 2, and HUI version 3 assessments at six planned points throughout treatment. Results/Anticipated Results: The first step of our analysis will be to ascertain agreement in scoring for parent–child dyads for the HUI2, HUI3, and CHRIs scores by comparing mean scores via two-sample t-testing. Bland–Altman plots will be constructed to compare agreement between the scores for HUI2/3 and the CHRIs. Similarly, Spearman’s correlation coefficients will be calculated for CHRIs with HUI2/3 for both parents and children. We hypothesize the CHRIs and HUI scores should roughly correlate with one another, but there may be divergence of correlation because the HUI has greater emphasis on functionality (e.g., sensation, mobility), and the CHRIs further emphasize social and emotional well-being in addition to physical health. Discussion/Significance of Impact: The composite score of the HUI 2/3 has allowed for direct comparison with other global HRQoL measures, providing greater clarity of its performance in different patient populations and clinical settings. The current study will improve understanding of the HUI 2/3 performance in a pediatric cancer population over time.

Purpose To test whether longitudinally measured health-related quality of life (HRQL) predicts transplant-related mortality (TRM) in pediatric hematopoietic stem cell transplant (HSCT). Methods The predictors of interest were emotional functioning, physical functioning, role functioning, and global HRQL, as rated by the parent about the child up to 6 times over 12 months of follow-up and measured by the Child Health Ratings Inventories. We used joint models, specifically shared parameter models, with time to TRM as the outcome of interest and other causes of mortality as a competing risk, via the JM software package in R. Choosing shared parameter models instead of standard survival models, such as Cox models with time-dependent covariates, enabled us to address measurement error in the HRQL trajectories and appropriately handle missing data. The nonlinear trajectories for each HRQL domain were modeled by random spline functions. The survival submodels were adjusted for baseline patient, family, and transplant characteristics. Results Hazard ratios per one-half standard deviation difference in emotional, physical, and role functioning, and global HRQL were 0.61 (95 % CI 0.46-0.81; p < 0.001), 0.70 (0.51-0.96; p = 0.03), 0.54 (0.34-0.85; p = 0.007), and 0.57 (0.41-0.79; p < 0.001), respectively. Conclusions HRQL trajectories were predictive of TRM in pediatric HSCT, even after adjusting the survival outcome for baseline characteristics.

Background When a child undergoes hematopoietic cell transplantation (HCT), the impact extends to the entire family, including siblings. Assessment of the quality of life (QoL) of siblings is challenged by their general lack of availability for regular assessment by clinical providers. Thus, the use of parent proxy reporting may be useful. Our aim was to describe the QoL of siblings of HCT survivors, as reported by their parents, as well as to identify parent and family factors associated with lower sibling QoL. Methods A cross-sectional study was utilized to assess parent-reported QoL of the HCT recipient’s sibling (Short Form (SF)-10 Health Survey for Children and the Pediatric Symptom Checklist (PSC)-17). Parent QoL was assessed using the SF-12. Multivariable linear regression was used to explore hypothesized predictors of sibling QoL, including parent QoL, family impact/function (Impact on Family Scale, Family Adaptability and Cohesion Evaluation Scales, IV, and a question asking about financial problems) while adjusting for demographic and HCT characteristics. Results Ninety-seven siblings (55% males) with a mean age of 12 years (standard deviation [SD] 4 years) were assessed, representing HCT survivors, who were an average of 5 years (SD 4 years) post-HCT. Neither sibling psychosocial (mean 49.84, SD 10.70, p  = 0.87) nor physical health scores (mean 51.54, SD 8.42, p  = 0.08) differed from norms. Parent proxies reported behavioral/emotional problems (PSC-17 total score  >  15) in 24% of siblings. While parental ratings of their own physical health (SF-12 were higher than norms (mean 53.04, SD 8.17, p  = 0.0005), mental health scores were lower (mean 45.48, SD 10.45, p  < 0.0001). In multivariable analysis, lower parent emotional functioning and adverse family function were associated with lower sibling QoL, as reported by parents. Conclusions While proxy-reported QoL of siblings did not differ significantly from normative data, both parent QoL and family function were associated with sibling QoL. Future research is needed to understand how siblings themselves perceive their QoL following HCT.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is an under-recognized complication of several chemotherapy agents used as part of curative-intent therapy for Hodgkin Lymphoma (HL). In the absence of validated self- or proxy-report measures for children and adolescents, CIPN reporting has relied on clinician rating, with grading scales often restricted to severe manifestations. In a proof-of-concept study, we assessed the feasibility and psychometric performance of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx), a unidimensional CIPN symptom scale widely used adults with CIPN, in pediatric HL at risk for CIPN. Methods Youth (11+ years) and parents of all children (5–17.9 years) with newly diagnosed high-risk HL enrolled on Children’s Oncology Group AHOD1331 (NCT02166463) were invited to complete the FACT-GOG-Ntx and a health-related quality of life (HRQL) measure at pre-treatment (Time 1), and during cycles 2 (Time 2) and 5 (Time 3) of chemotherapy during the first half of study accrual. Clinical grading of CIPN by providers was also assessed using the Balis Pediatric Neuropathy Scale. We evaluated Cronbach’s alpha, construct validity, and agreement between raters. Change in FACT-GOG-Ntx scores over time was assessed using a repeated measures model. Results 306 patients had at least one completed FACT-GOG-Ntx with time-specific completion rates of > 90% for both raters. Cronbach’s alpha was > 0.7 for youth and parent-proxy report at all time points. Correlations between FACT-GOG-Ntx and HRQL scores were moderate (0.41–0.48) for youth and parent-proxy raters across all times. Youth and parent-proxy raters both reported worse FACT-GOG-Ntx scores at Time 3 for those who had clinically-reported CIPN compared to those who did not. Agreement between raters was moderate to high. Compared to baseline scores, those at Time 3 were significantly lower for youth (β = − 2.83, p  < 0.001) and parent-proxy raters (β = − 1.99, p  < 0.001). Conclusions High completion rates at all time points indicated feasibility of eliciting youth and parent report. Psychometric performance of the FACT-GOG-Ntx revealed acceptable reliability, evidence of validity, and strong inter-rater agreement, supporting the use of this self- or proxy-reported measure of CIPN in youth with high-risk HL exposed to tubulin inhibitors, as part of a Phase 3 clinical trial. Clinical trial information : Clinical Trials Registry, NCT02166463. Registered 18 June 2014, https://clinicaltrials.gov/ct2/show/study/NCT02166463

Background Pediatric health-related quality of life (HRQL) measures explore multiple domains of HRQL. To ease administration, burden, and implementation, we created a 7-item unidimensional global HRQL scale for children. This paper evaluates the psychometric properties of the global HRQL scale in children undergoing hematopoietic stem cell transplant (HSCT) and describes the trajectory of global HRQL scores over the 12-month course following HSCT. Methods As part of two longitudinal HSCT studies, HRQL was collected on 312 parent–child dyads using the Child Health Ratings Inventories. Parents of children aged 5–18 completed the pediatric global HRQL scale about their child and 117 adolescents completed the scale themselves. Psychometric properties were compared across both raters. Two repeated measures models were built to describe trajectories of (1) global HRQL for all children based on parent proxy report and (2) global HRQL for adolescents based on adolescent self-report and parent proxy report. Results Internal consistency reliability was high for parent proxy report and adolescent self-report (Cronbach’s alpha 0.9, 0.8, respectively). Unidimensionality was verified using principal components analysis. Both models indicated decreased global HRQL in the presence of early complications related to HSCT and Model 1 further indicated decreased HRQL in the presence of later complications. Model 2 showed that parent proxies reported lower global HRQL scores than adolescent self-report. Conclusions This study has demonstrated the unidimensionality and strong psychometric properties of a 7-item global HRQL scale in a sample of children undergoing HSCT. Despite its brevity, scale scores vary in clinically meaningful ways. Future applications of this scale are encouraged.

Objective: The number of children and adolescents (hereafter referred to as “children”) who have been prescribed second-generation antipsychotics (SGAs) has increased over the last decade, but little is known about monitoring practices in pediatric patients who are vulnerable to adverse effects. We examined factors associated with psychiatrists' self-reported monitoring of children who were prescribed SGAs. Methods: A survey was mailed to a national, randomly selected sample of 1600 child and adolescent psychiatrists from the American Medical Association mailing list. Using logistic regression, we tested whether psychiatrist characteristics, attitudes, and practice characteristics were associated with monitoring (baseline and/or periodic) the following: Patient history, height and weight, blood pressure, waist circumference, lipid and glucose levels, and electrocardiogram. Results: Among the analytic sample of 308, at least two thirds reported monitoring patient history, height and weight, blood pressure, and fasting plasma lipids and glucose; 23% reported monitoring waist circumference; and 12% reported conducting an electrocardiogram. More than one third stated that they routinely monitored thyroid levels and more than half reported monitoring complete blood count and electrolytes/blood urea nitrogen. Psychiatrists reporting that they were able to measure vital signs on site were more likely to measure height and weight. Those who reported feeling comfortable conducting a physical examination were more likely to measure blood pressure. Those answering that the risk of metabolic syndrome was low were less likely to measure blood pressure and waist circumference. Being board certified and able to measure vital signs on site were associated with more monitoring of glucose and lipid levels. Conversely, years in practice and feeling that patients were nonadherent with blood work were associated with less monitoring of glucose and lipid levels. Conclusions: In this sample, inconsistent monitoring patterns of children prescribed SGAs were found. Efforts to communicate guidelines' evidence base and improve office capacity to measure and track adverse effects are needed to increase appropriate adverse effect monitoring in children who have been prescribed SGAs.

Adolescents and young adults (AYA) with lymphoma experience treatment‐related effects in the short and long term that impact their quality of life and survivorship experience. The effort to improve outcomes for AYA lymphoma survivors requires understanding the available literature, identifying current knowledge deficits, designing better clinical trials incorporating the patient perspective, using novel tools to bridge data gaps and building survivorship guidelines that translate research to clinical practice. This review article summarizes the current state of lymphoma treatment‐related outcomes in AYAs and provides future direction.

Acute myeloid leukemia (AML) is associated with frequent hospitalizations. We evaluated factors associated with length of stay (LOS) and charge per day (CPD) for admissions in older (≥60 years) and younger patients (<60 years). We identified patients with ICD‐9‐CM codes for AML or myeloid sarcoma in the 2012 HCUP‐NIS. In separate models based on age, we examined patient (sex, race, income, insurance payer, chronic conditions, chemotherapy administration, death) and hospital (type, geography) characteristics. Multivariable negative binomial regression estimated factor effects on LOS and CPD using rate ratios, with HCUP‐NIS weights. In 43,820 discharges, LOS was longer in patients <60 than ≥60 (6.8 vs. 5.4 days). For patients <60, longer LOS was seen with more chronic conditions (RR = 1.10), Black race (RR = 1.16), chemotherapy (RR = 2.27), and geography; shorter LOS was associated with older age (RR = 0.93), Medicare (RR = 0.83), and hospital type. For patients ≥60, longer LOS associated with chronic conditions (RR = 1.07) and Asian race (RR = 1.33). Shorter LOS associated with older age (RR = 0.86), higher income (RR = 0.93), and hospital type. For patients <60, higher CPD associated with chronic conditions (RR = 1.05), death (RR = 1.93), and geography; lower CPD associated with increasing age (RR = 0.96), Medicaid (RR = 0.93), and rural hospitals (RR = 0.65). For patients ≥60, higher CPD associated with Medicare (RR = 1.05), more chronic conditions (RR = 1.02), younger age (RR = 1.1), west geography (RR = 1.37), death (RR = 1.45), and Hispanic race (RR = 1.15). We identify predictors for increased healthcare utilization in hospitalized patients with AML, which differ within age groups. Future efforts are needed to link utilization outcomes with clinical treatments and response. Acute myeloid leukemia is associated with thousands of hospital admissions annually. We identify risk factors for increased healthcare utilization in younger and older hospitalized patients with AML.