Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia.

2023

222-229

02/2023

1559-6834

BACKGROUND: Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.

OBJECTIVE: To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.

METHODS: We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.

RESULTS: The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.

CONCLUSIONS: In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

10.1017/ice.2022.82

Infect Control Hosp Epidemiol

35465865

Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy.

2023

609-619

02/2023

1528-0020

Children living in poverty experience excessive relapse and death from newly diagnosed acute lymphoblastic leukemia (ALL). The influence of household poverty and neighborhood social determinants on outcomes from chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory (r/r) leukemia is poorly described. We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020. Socioeconomic status (SES) was proxied at the household level, with poverty exposure defined as Medicaid-only insurance. Low-neighborhood opportunity was defined by the Childhood Opportunity Index. Among 206 patients aged 1 to 29, 35.9% were exposed to household poverty, and 24.9% had low-neighborhood opportunity. Patients unexposed to household poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with a high disease burden (>25%), a disease characteristic associated with inferior outcomes, as compared with less advantaged patients (38% vs 30%; 37% vs 26%). Complete remission (CR) rate was 93%, with no significant differences by household poverty (P = .334) or neighborhood opportunity (P = .504). In multivariate analysis, patients from low-opportunity neighborhoods experienced an increased hazard of relapse as compared with others (P = .006; adjusted hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.3-4.1). There was no difference in hazard of death (P = .545; adjusted HR, 1.2; 95% CI, 0.6-2.4). Among children who successfully receive CAR T-cell therapy, CR and overall survival are equitable regardless of proxied SES and neighborhood opportunity. Children from more advantaged households and neighborhoods receive CAR T-cell therapy with a higher disease burden. Investigation of multicenter outcomes and access disparities outside of clinical trial settings is warranted.

10.1182/blood.2022017866

Blood

36351239

Racial and ethnic disparities in childhood and young adult acute lymphocytic leukaemia: secondary analyses of eight Children's Oncology Group cohort trials.

2023

e129-e141

02/2023

2352-3026

BACKGROUND: Previous studies have identified racial and ethnic disparities in childhood acute lymphocytic leukaemia survival. We aimed to establish whether disparities persist in contemporaneous cohorts and, if present, are attributable to differences in leukaemia biology or insurance status.

METHODS: Patients with newly diagnosed acute lymphocytic leukaemia in inpatient and outpatient centres in the USA, Canada, Australia, and New Zealand, aged 0-30 years, who had race or ethnicity data available, enrolled on eight completed Children's Oncology Group trials (NCT00103285, NCT00075725, NCT00408005, NCT01190930, NCT02883049, NCT02112916, NCT02828358, and NCT00557193) were included in this secondary analysis. Race and ethnicity were categorised as non-Hispanic White, Hispanic, non-Hispanic Black, non-Hispanic Asian, and non-Hispanic other. Event-free survival and overall survival were compared across race and ethnicity groups. The relative contribution of clinical and biological disease prognosticators and insurance status was examined through multivariable regression models, both among the entire cohort and among those with B-cell lineage versus T-cell lineage disease.

FINDINGS: Between Jan 1, 2004, and Dec 31, 2019, 24 979 eligible children, adolescents, and young adults with acute lymphocytic leukaemia were enrolled, of which 21 152 had race or ethnicity data available. 11 849 (56·0%) were male and 9303 (44·0%) were female. Non-Hispanic White patients comprised the largest racial or ethnic group (13 872 [65·6%]), followed by Hispanic patients (4354 [20·6%]), non-Hispanic Black patients (1517 [7·2%]), non-Hispanic Asian (n=1071 [5·1%]), and non-Hispanic other (n=338 [1·6%]). 5-year event-free survival was 87·4% (95% CI 86·7-88·0%) among non-Hispanic White patients compared with 82·8% (81·4-84·1%; hazard ratio [HR] 1·37, 95% CI 1·26-1·49; p<0·0001) among Hispanic patients and 81·8% (79·3-84·0; HR 1·45, 1·28-1·65; p<0·0001) among non-Hispanic Black patients. Non-hispanic Asian patients had a 5-year event-free survival of 88·1% (95% CI 85·5-90·3%) and non-Hispanic other patients had a survival of 82·8% (76·4-87·6%). Inferior event-free survival among Hispanic patients was substantially attenuated by disease prognosticators and insurance status (HR decreased from 1·37 [1·26-1·49; p<0·0001] to 1·11 [1·00-1·22; p=0·045]). The increased risk among non-Hispanic Black patients was minimally attenuated (HR 1·45 [1·28-1·65; p<0·0001] to 1·32 [1·14-1·52; p<0·0001]). 5-year overall survival was 93·6% (91·5-95·1%) in non-Hispanic Asian patients, 93·3% (92·8-93·7%) in non-Hispanic White patients, 89·9% (88·7-90·9%) in Hispanic, 89·7% (87·6-91·4%) in non-Hispanic Black patients, 88·9% (83·2-92·7%) in non-Hispanic other patients. Disparities in overall survival were wider than event-free survival (eg, among non-Hispanic other patients, the HR for event-free survival was 1·43 [1·10-1·85] compared with 1·74 [1·27-2·40] for overall survival). Disparities were restricted to patients with B-cell acute lymphocytic leukaemia, no differences in event-free survival or overall survival were seen in the T-cell acute lymphocytic leukaemia group.

INTERPRETATION: Substantial disparities in outcome for B-cell acute lymphocytic leukaemia persist by race and ethnicity, but are not observed in T-cell acute lymphocytic leukaemia. Future studies of relapsed patients, access to and quality of care, and other potential aspects of structural racism are warranted to inform interventions aimed at dismantling racial and ethnic disparities.

FUNDING: National Cancer Institute and St Baldrick's Foundation.

10.1016/S2352-3026(22)00371-4

Lancet Haematol

36725118

Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy.

2022

11/2022

1528-0020

Children living in poverty experience excess relapse and death from newly diagnosed acute lymphoblastic leukemia (ALL). The influence of household poverty and neighborhood social determinants on outcomes from CAR T-cell therapy for relapsed/refractory (r/r) leukemia is poorly described. We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020. Socioeconomic status (SES) was proxied at the household-level, with poverty-exposure defined as Medicaid-only insurance. Low neighborhood opportunity was defined by the Childhood Opportunity Index. Among 206 patients aged 1-29, 35.9% were household-poverty exposed, and 24.9% had low neighborhood opportunity. Patients unexposed to household-poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with high disease burden (>25%)-a disease characteristic associated with inferior outcomes-as compared to less advantaged patients (38% vs 30%; 37% vs 26%). Complete remission (CR) rate was 93% with no significant differences by household-poverty (P = 0.334) or neighborhood opportunity (P = 0.504). In multivariate analysis, patients from low-opportunity neighborhoods experienced increased hazard of relapse as compared to others (P = 0.006, adjusted HR 2.3, 95% CI 1.3-4.1). There was no difference in hazard of death (P = 0.545, adjusted HR 1.2, 95% CI 0.6-2.4). Among children who successfully receive CAR T-cell therapy, CR and OS is equitable regardless of proxied SES and neighborhood opportunity. Children from more advantaged households and neighborhoods receive CAR T-cell therapy with higher disease burden. Investigation of multicenter outcomes and access disparities outside of clinical-trial settings is warranted. Clinical trials: NCT01626495; NCT02435849 ; NCT02374333; NCT02228096; NCT02906371.

10.1182/blood.2022017866

Blood

36351239

Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia.

2022

1-8

2022 Apr 25

1559-6834

<p><strong>BACKGROUND: </strong>Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.</p>

<p><strong>OBJECTIVE: </strong>To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.</p>

<p><strong>METHODS: </strong>We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.</p>

<p><strong>RESULTS: </strong>The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.</p>

<p><strong>CONCLUSIONS: </strong>In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.</p>

10.1017/ice.2022.82

Infect Control Hosp Epidemiol

35465865

Medical Outcomes, Quality of Life, and Family Perceptions for Outpatient vs Inpatient Neutropenia Management After Chemotherapy for Pediatric Acute Myeloid Leukemia.

2021

e2128385

2021 Oct 01

2574-3805

<p><strong>Importance: </strong>Pediatric acute myeloid leukemia (AML) requires multiple courses of intensive chemotherapy that result in neutropenia, with significant risk for infectious complications. Supportive care guidelines recommend hospitalization until neutrophil recovery. However, there are little data to support inpatient over outpatient management.</p>

<p><strong>Objective: </strong>To evaluate outpatient vs inpatient neutropenia management for pediatric AML.</p>

<p><strong>Design, Setting, and Participants: </strong>This cohort study used qualitative and quantitative methods to compare medical outcomes, patient health-related quality of life (HRQOL), and patient and family perceptions between outpatient and inpatient neutropenia management. The study included patients from 17 US pediatric hospitals with frontline chemotherapy start dates ranging from January 2011 to July 2019, although the specific date ranges differed for the individual analyses by design and relative timing. Data were analyzed from August 2019 to February 2020.</p>

<p><strong>Exposures: </strong>Discharge to outpatient vs inpatient neutropenia management.</p>

<p><strong>Main Outcomes and Measures: </strong>The primary outcomes of interest were course-specific bacteremia incidence, times to next course, and patient HRQOL. Course-specific mortality was a secondary medical outcome.</p>

<p><strong>Results: </strong>Primary quantitative analyses included 554 patients (272 [49.1%] girls and 282 [50.9%] boys; mean [SD] age, 8.2 [6.1] years). Bacteremia incidence was not significantly different during outpatient vs inpatient management (67 courses [23.8%] vs 265 courses [29.0%]; adjusted rate ratio, 0.73; 95% CI, 0.56 to 1.06; P = .08). Outpatient management was not associated with delays to the next course compared with inpatient management (mean [SD] 30.7 [12.2] days vs 32.8 [9.7] days; adjusted mean difference, -2.2; 95% CI, -4.1 to -0.2, P = .03). Mortality during intensification II was higher for patients who received outpatient management compared with those who received inpatient management (3 patients [5.4%] vs 1 patient [0.5%]; P = .03), but comparable with inpatient management at other courses (eg, 0 patients vs 5 patients [1.3%] during induction I; P = .59). Among 97 patients evaluated for HRQOL, outcomes did not differ between outpatient and inpatient management (mean [SD] Pediatric Quality of Life Inventory total score, 70.1 [18.9] vs 68.7 [19.4]; adjusted mean difference, -2.8; 95% CI, -11.2 to 5.6). A total of 86 respondents (20 [23.3%] in outpatient management, 66 [76.7%] in inpatient management) completed qualitative interviews. Independent of management strategy received, 74 respondents (86.0%) expressed satisfaction with their experience. Concerns for hospital-associated infections among caregivers (6 of 7 caregiver respondents [85.7%] who were dissatisfied with inpatient management) and family separation (2 of 2 patient respondents [100%] who were dissatisfied with inpatient management) drove dissatisfaction with inpatient management. Stress of caring for a neutropenic child at home (3 of 3 respondents [100%] who were dissatisfied with outpatient management) drove dissatisfaction with outpatient management.</p>

<p><strong>Conclusions and Relevance: </strong>This cohort study found that outpatient neutropenia management was not associated with higher bacteremia incidence, treatment delays, or worse HRQOL compared with inpatient neutropenia management among pediatric patients with AML. While outpatient management may be safe for many patients, course-specific mortality differences suggest that outpatient management in intensification II should be approached with caution. Patient and family experiences varied, suggesting that outpatient management may be preferred by some but may not be feasible for all families. Further studies to refine and standardize safe outpatient management practices are warranted.</p>

10.1001/jamanetworkopen.2021.28385

JAMA Netw Open

34709389

Pediatric palliative care parents' distress, financial difficulty, and child symptoms.

2021

2021 Aug 20

1873-6513

<p><strong>CONTEXT: </strong>Parents of patients with a serious illness experience psychological distress, which impacts parents' wellbeing and, potentially, their ability to care for their children. Parent psychological distress may be influenced by children's symptom burden and by families' financial difficulty.</p>

<p><strong>OBJECTIVES: </strong>This study examined the associations among parent psychological distress, parent-reported patient symptoms, and financial difficulty, seeking to determine the relative association of financial difficulty and of patient symptoms to parent psychological distress.</p>

<p><strong>METHODS: </strong>Cross-sectional study of baseline data for 601 parents of 532 pediatric palliative care patients enrolled in a prospective cohort study conducted at seven US children's hospitals. Data included self-reported parent psychological distress and parent report of child's symptoms and family financial difficulty. We used ordinary least squares multiple regressions to examine the association between psychological distress and symptom score, between psychological distress and financial difficulty, and whether the degree of financial difficulty modified the relationship between psychological distress and symptom score.</p>

<p><strong>RESULTS: </strong>The majority of parents were moderately distressed (52%) or severely distressed (17%) and experienced some degree of financial difficulty (65%). While children's symptom scores and family financial difficulty together explained more of the variance in parental psychological distress than either variable alone, parental distress was associated more strongly, and to a larger degree, with financial difficulty than with symptom scores alone.</p>

<p><strong>CONCLUSIONS: </strong>Parent psychological distress was associated with parent-reported patient symptoms and financial difficulty. Future work should examine these relationships longitudinally, and whether interventions to improve symptom management and ameliorate financial difficulties improve parental outcomes.</p>

10.1016/j.jpainsymman.2021.08.004

J Pain Symptom Manage

34425212

Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

2020

2020 Nov 24

1460-2105

<p><strong>BACKGROUND: </strong>Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided.</p>

<p><strong>RESULTS: </strong>In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P &lt; .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P &lt; .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P &lt; .001) compared with the unexposed group.</p>

<p><strong>CONCLUSIONS: </strong>Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.</p>

10.1093/jnci/djaa107

J Natl Cancer Inst

33227816

Pediatric Palliative Care in the Multi-Cultural Context: Findings from a workshop conference.

2019

2019 Jan 24

1873-6513

<p><strong>CONTEXT: </strong>In our increasingly multicultural society, providing sensitive and respectful pediatric palliative care is vital.</p>

<p><strong>OBJECTIVES: </strong>We held a one-day workshop conference with stakeholders and pediatric clinicians to identify suggestions for navigating conflict when cultural differences are present and for informing standard care-delivery.</p>

<p><strong>METHODS: </strong>Participants explored cases in one of four workshops focused on differences based on either race/ethnicity, economic disparity, religion/spirituality, or family-values. Each workshop was facilitated by two authors; separate transcriptionists recorded workshop discussions in real-time. We used content analyses to qualitatively evaluate the texts and generate recommendations.</p>

<p><strong>RESULTS: </strong>Participants included 142 individuals representing over 6 unique disciplines, 25 of the United States, and 3 nations. Whereas the conference focused on pediatric palliative care, findings were broadly generalizable to most medical settings. Participants identified key reasons cultural differences may create tension and then provided frameworks for communication, training, and clinical care. Specifically, recommendations included phrases to navigate emotional conflict, broken trust, unfamiliar family values, and conflict. Suggested approaches to training and clinical care included the development of core competencies in communication, history taking, needs assessment, and emotional intelligence. Important opportunities for scholarship included qualitative studies exploring diverse patient- and family-experiences, quantitative studies examining health disparities, and randomized clinical trials testing interventions designed to improve community partnerships, communication, or child health outcomes.</p>

<p><strong>CONCLUSION: </strong>Taken together, findings provide a foundation for collaboration between patients, families, and clinicians of all cultures.</p>

10.1016/j.jpainsymman.2019.01.005

J Pain Symptom Manage

30685496

The Relationship Between Household Income and Patient-Reported Symptom Distress and Quality of Life in Children With Advanced Cancer: A Report From the PediQUEST Study.

2018

2018 Sep 14

1097-0142

<p><strong>BACKGROUND: </strong>Children with advanced cancer experience high symptom distress, which negatively impacts their health-related quality of life (HRQOL). To the authors' knowledge, the relationship between income and symptom distress and HRQOL is not well described.</p>

<p><strong>METHODS: </strong>The Pediatric Quality of Life and Symptoms Technology (PediQUEST) multisite clinical trial evaluated an electronic patient-reported outcome system to describe symptom distress and HRQOL in children with advanced cancer via repeated surveys. The authors performed a secondary analysis of PediQUEST data for those children with available parent-reported household income (dichotomized at 200% of the Federal Poverty Level and categorized as low income [&lt;$50,000/year] or high income [≥$50,000/year]). The prevalence of the 5 most commonly reported physical and psychological symptoms was compared between groups. Multivariable generalized estimating equation models were used to test the association between household income and symptom distress and HRQOL.</p>

<p><strong>RESULTS: </strong>A total of 78 children were included in the analyses: 56 (72%) in the high-income group and 22 (28%) in the low-income group. Low-income children were more likely to report pain than high-income children (64% vs 42%; P=.02). In multivariable models, children from low-income families demonstrated a uniform trend toward higher total (β =3.1; 95% confidence interval [95% CI], -0.08 to 6.2 [P=.06]), physical (β=3.8; 95% CI, -0.4 to 8.0 [P=.09]), and psychological (β=3.46; 95% CI, -1.91 to 8.84 [P=.21]) symptom distress compared with children from high-income families. Low income was associated with a uniform trend toward lower total (β=-7.9; 95% CI, -14.8, to -1.1 [P=.03]), physical (β=-11.2; 95% CI, -21.2 to -1.2 [P=.04]), emotional (β=-5.8; 95% CI, -13.6 to 2.0 [P=.15]), social (β=-2.52; 95% CI, -9.27 to 4.24 [P=.47]), and school (β=-9.8; 95% CI, -17.8 to -1.8 [P=.03]) HRQOL.</p>

<p><strong>CONCLUSIONS: </strong>In this cohort of children with advanced cancer, children from low-income families were found to experience higher symptom burden and worse QOL.</p>

10.1002/cncr.31668

Cancer

30216416