Adolescents and young adults (AYA) with cancer: the clinical course of COVID-19 infections.

Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.

Improving Time to Antibiotic Administration for Pediatric Oncology Patients With New-Onset Fever.

PURPOSE: Time to antibiotic administration (TTA) in <60 minutes for children with neutropenic fever presenting to an emergency room is associated with reduced incidence of sepsis and intensive care admission. As such, TTA is used as a national quality metric for pediatric oncology patients. At our center, in 2020, 19% of the hospitalized patients with a new fever encounter were receiving antibiotics in <60 minutes, prompting a multidisciplinary approach to reach a goal of >90% in all pediatric patients with cancer with a new fever. METHODS: A multidisciplinary team completed four Plan-Do-Study-Act cycles between March 2021 and September 2023. We implemented education initiatives, an updated handoff smartphrase guiding the on-call team, an antibiotic champion (AC) nursing role, a revised fever plan for handoff, a rapid-response team to address new fevers, and an algorithm for blood culture collection. Data were collected, analyzed, and reported biweekly with feedback sought for delays in TTA. RESULTS: There was a total of 639 new fevers in 329 unique oncology patients. As of September 4, 2023, average TTA decreased from 89 minutes at baseline to 46.4 minutes for more than 12 months. The percentage of patients receiving first dose of antibiotic in <60 minutes also increased from 19% to 93.7%, which was sustained as well. The most effective interventions were creation of the AC role and streamlining the blood culture collection process. CONCLUSION: This project demonstrates the importance of multidisciplinary involvement for providing optimal care. Specific implementation of targeted education, an AC role, and development of an algorithm streamlining the processes led to meaningful targeted improvements. Further analyses will explore the impact of these interventions on patient outcomes.

Children's Oncology Group's 2023 blueprint for research: Cancer control and supportive care.

The objective of the Cancer Control and Supportive Care (CCL) Committee in the Children's Oncology Group (COG) is to reduce the overall morbidity and mortality of therapy-related toxicities in children, adolescents, and young adults with cancer. We have targeted five major domains that cause clinically important toxicity: (i) infections and inflammation; (ii) malnutrition and metabolic dysfunction; (iii) chemotherapy-induced nausea and vomiting; (iv) neuro- and oto-toxicty; and (v) patient-reported outcomes and health-related quality of life. Subcommittees for each domain prioritize randomized controlled trials and biology aims to determine which strategies best mitigate the toxicities. The findings of these trials are impactful, informing clinical practice guidelines (CPGs) and directly leading to changes in the standard of care for oncology practice. With the development of new therapies, there will be new toxicities, and the COG CCL Committee is dedicated to developing interventions to minimize acute and delayed toxicities, lessen morbidity and mortality, and improve quality of life in pediatric and young adult patients with cancer.

Clinical Features and Risk Factors Associated With Multisystem Inflammatory Syndrome in Children With Cancer and COVID-19.

Importance: Little is known about the risk of post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) in the setting of childhood cancer. Objective: To evaluate factors associated with MIS-C and describe the clinical course of COVID-19 in the setting of MIS-C. Design, Setting, and Participants: Multisite observational cohort study of a registry representing more than 100 US pediatric oncology sites. All included patients were registered between April 1, 2020, and May 18, 2022. Sites submitted deidentified data surrounding sociodemographics, cancer diagnosis and treatment, and COVID-19 course (symptoms, maximum support required, outcome). Patients with MIS-C (n = 24) were compared with matched controls (n = 96). Children (<21 years) with cancer who developed COVID-19 while receiving cancer treatment or within 1 year of completing treatment were characterized based on their development of MIS-C. Exposures: (1) Clinical and sociodemographic characteristics of children with cancer and COVID-19; and (2) MIS-C. Main Outcomes and Measures: (1) Development of MIS-C among children with cancer and COVID-19; and (2) symptoms and disease severity associated with MIS-C. Results: Among 2035 children with cancer and COVID-19, 24 (1.2%) developed MIS-C. COVID-19 occurred at a median (IQR) age of 12.5 (5.5-17.1) years in those with MIS-C and 11 (6-16) years among matched controls (P = .86). The majority of children with MIS-C had a hematologic cancer (83.3% [n = 20]), were publicly insured (66.7% [n = 16]), and were Hispanic (54.2% [n = 13]). Half (n = 12) had 1 or more noncancer comorbidity. Those with comorbidities were more likely to develop MIS-C than those without (odds ratio [OR], 2.5 [95% CI, 1.1-5.7]). Among children with MIS-C, 100% (n = 24) were admitted to the hospital and 54.2% (n = 13) to the intensive care unit (ICU), while COVID-19 contributed to the death of 20.1% (n = 5); cancer therapy was changed in 62.5% (n = 15). Compared with matched controls, those with MIS-C had higher odds of symptoms classified as systemic (OR, 4.7 [95% CI, 1.4-15.8]) or gastrointestinal (OR, 5.0 [95% CI, 1.7-14.6]) along with higher odds of hospitalization (OR, 42.9 [95% CI, 7.1-258]), ICU admission (OR, 11.4 [95% CI, 3.6-36.4]), and changes to cancer therapy (OR, 24.9 [95% CI, 6.5-94.8]). Conclusions and Relevance: In this cohort study among children with cancer and COVID-19, those with MIS-C had a more severe clinical course than those without MIS-C. The risk of MIS-C and its severity are important to consider as clinicians monitor patients with COVID-19. These findings can inform their conversations with families regarding COVID-19 risks and the benefits of prevention strategies that are pharmacologic (vaccination) and nonpharmacologic (masking), as well as treatment (antivirals, monoclonal antibodies).

Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience.

The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions' experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6-21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), IDH1/2 (n = 2), monosomy 5 (n = 1), NUP98 (n = 1) and ASXL1 (n = 1). The majority (86%) received venetoclax with a hypomethylating agent. Grade 3 or 4 adverse events included febrile neutropenia in 37% (n = 16), non-febrile neutropenia in 12% (n = 5), anemia in 14% (n = 6), and thrombocytopenia in 14% (n = 6). Of 40 patients evaluable for response, 10 patients (25%) achieved complete response (CR), 6 patients (15%) achieved CR with incomplete blood count recovery (CRi), and 2 patients (5%) had a partial response, (CR/CRi composite = 40%; ORR = 45%). Eleven (25%) patients received a hematopoietic stem cell transplant following venetoclax combination therapy, and six remain alive (median follow-up time 33.6 months). Median event-free survival and overall survival duration was 3.7 months and 8.7 months, respectively. Our findings suggest that in pediatric patients with AML, venetoclax is well-tolerated, with a safety profile similar to that in adults. More studies are needed to establish an optimal venetoclax-based regimen for the pediatric population.

Fertility Preservation Practices at Pediatric Oncology Institutions in the United States: A Report From the Children's Oncology Group.

PURPOSE: Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS: A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients (P = .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males (P < .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION: Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

Inclusion of a core patient-reported outcomes battery in adolescent and young adult cancer clinical trials.

Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute's Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer.

Sinusoidal Obstruction Syndrome of the Liver Associated With 6-Mercaptopurine During Maintenance in a Child With T-cell Acute Lymphoblastic Leukemia.

Sinusoidal obstruction syndrome (SOS) of the liver is a complication of chemotherapy most often encountered with hematopoietic stem cell transplant due to high-dose conditioning regimens, but it can also occur with regimens outside of the transplant setting. Mild-to-moderate SOS is a well-described 6-thioguanine toxicity; however, it has rarely been reported as secondary to 6-mercaptopurine, a related thiopurine. This report details a case of a 10-year-old male with T-cell acute lymphoblastic leukemia who developed severe SOS during maintenance therapy with 6-mercaptopurine, and a review of the related literature.

Change in the Parent-Clinician Relationship Throughout the First Year of Treatment in Pediatric Oncology.

Importance: Challenges in the therapeutic relationship between clinicians and parents of children with cancer have been shown to emerge immediately after diagnosis, but little is known about whether such relationships improve over time. Objective: To better understand the potential evolution of parent-clinician relationships over the first year after diagnosis of pediatric cancer. Design, Setting, and Participants: This survey study was conducted from November 2015 to September 2020 at Dana-Farber Cancer Institute/Boston Children's Hospital and Texas Children's Hospital. Participants were oncology clinicians (attending physicians and fellows or nurse practitioners) and parents of children (aged <18 years) with a cancer diagnosis. Surveys were completed at study enrollment (soon after diagnosis [baseline]) and at the 3-month and 12-month follow-up. Exposures: Children had to have had at least 3 previous clinical visits with a primary oncology clinician. Main Outcomes and Measures: Survey instruments included the parent and clinician versions of the Relationship Challenges Scale, and factors associated with changes in relationships, including parental, clinician, and health care system attributes, were measured. Results: Survey participants included 150 parents (118 women [78.7%]; 98 with White race and ethnicity [65.3%]) and 49 clinicians (39 [79.6%] women; 39 with White race and ethnicity [79.6%]). Parents reported on 175 relationships with clinicians, and clinicians reported on 98 relationships with parents at all 3 time points (baseline, 3-month follow-up, and 12-month follow-up). Of the 175 relationships, 33 (18.9%) were considered to be challenging by parents at baseline, 27 (15.4%) were considered to be challenging at the 3-month follow-up, and 32 (18.3%) were considered to be challenging at the 12-month follow-up. Of the 33 challenging relationships at baseline, 20 (60.6%) resolved at the 12-month follow-up, whereas 13 (39.4%) had persistent challenges. However, 19 relationships that were not challenging at baseline had new challenges at the 12-month follow-up, corresponding to 59.4% of all challenges at the 12-month follow-up. No clinician behaviors were associated with improvement. Strategies used frequently (≥50%) by clinicians in their relationships that were associated with improvement included holding family meetings, apologizing, adapting to the parent's communication style, and devoting extra time and attention. Conclusions and Relevance: Results of this study showed that some parents experienced challenging relationships with their child's oncology clinicians beginning at diagnosis and throughout the first year after diagnosis. Although many such relationships improved, others worsened, reflecting the vulnerable and stressful nature of parent-clinician relationships.

Ventricular assist device support for children with chemotherapy-induced cardiomyopathy and advanced heart failure: Perspectives gained from a single-center experience.

BACKGROUND: Guidance and data on ventricular assist device (VAD) support for children with chemotherapy-induced cardiomyopathy, particularly within the first 2 years after chemotherapy, are limited. METHODS: We performed a single-center retrospective case series, reviewing medical records of children <18 years of age with chemotherapy-induced cardiomyopathy and advanced heart failure (HF) who received durable VAD support. RESULTS: Six patients met inclusion criteria-5 HeartWare™ HVAD, 1 Berlin Heart EXCOR® . Median age at cancer diagnosis was 6 years (IQR 4.5-10 years). Median dose of anthracycline received was 540 mg/m2 (IQR 450-630 mg/m2 ). All patients developed HF within 1 year after initiation of cancer treatment (median 8 months, IQR 6-11.5 months) and were initiated on durable VAD support at a median of 8 months after completion of cancer treatment (IQR 3.3-43.5 months). Four patients had significant right ventricular dysfunction needing oral pulmonary vasodilator therapy, one patient had a major bleeding complication, and two patients had thromboembolic strokes while on VAD support. Median duration of VAD support was 7.5 months (IQR 3-11.3 months). Two patients underwent VAD explant due to recovery of LV function, one died due to cancer progression, and three underwent heart transplantation. CONCLUSIONS: Durable VAD support should be considered as a therapeutic option for children who have advanced HF due to chemotherapy-induced cardiomyopathy, even within 2 years of completing cancer treatment. A multi-disciplinary approach is essential for appropriate patient selection prior to implant and to ensure comprehensive care throughout the duration of VAD support.

Levofloxacin prophylaxis for pediatric leukemia patients: Longitudinal follow-up for impact on health care-associated infections.

BACKGROUND: Bloodstream infections (BSIs) cause morbidity and mortality in pediatric patients with leukemia. Antibiotic prophylaxis during periods of chemotherapy-induced neutropenia may reduce the incidence of BSIs. PROCEDURE: A levofloxacin prophylaxis guideline was implemented for pediatric patients with acute myeloid leukemia and relapsed acute lymphoblastic leukemia. We conducted a retrospective cohort study over 4 years (2 years pre and 2 years post implementation) of the practice guideline to assess the impact on central line-associated bloodstream infections (CLABSI) and BSI events. Secondary outcomes included incidence of Clostridioides difficile-associated diarrhea, bacteremia due to multidrug-resistant organisms (MDRO), and bacteremia due to levofloxacin nonsusceptible organisms. STATA was used for data analysis. RESULTS: Sixty-three and 72 patients met inclusion criteria for the pre- and postimplementation cohorts, respectively. Demographics were similar between the groups. We observed 60 BSI events in the pre-group versus 49 events in the post-group (p = .1). Bacteremia due to Gram-negative rods (risk ratio [RR] 0.37 [0.21, 0.66], p < .001) and National Healthcare Safety Network (NHSN) CLABSIs (RR 0.62 [0.44, 0.89], p = .01) were significantly reduced in the postimplementation group. The incidences of C. difficile-associated diarrhea and MDRO bacteremia were similar between groups. However, we observed an increase in the incidence of BSI due to Gram-negative rods that were nonsusceptible to levofloxacin (RR 3.38 [0.72, 6.65], p < .001). CONCLUSION: Following implementation of a levofloxacin prophylaxis guideline, we observed a significant decrease in BSIs due to Gram-negative rods and NHSN CLABSIs. Vigilant monitoring of outcomes post guideline implementation is critical to track emergence of resistant organisms.

Infrastructure of Fertility Preservation Services for Pediatric Cancer Patients: A Report From the Children's Oncology Group.

PURPOSE: Fertility preservation (FP) services are part of comprehensive care for those newly diagnosed with cancer. The capacity to offer these services to children and adolescents with cancer is unknown. METHODS: A cross-sectional survey was sent to 220 Children's Oncology Group member institutions regarding institutional characteristics, structure and organization of FP services, and barriers to FP. Standard descriptive statistics were computed for all variables. The association between site-specific factors and selected outcomes was examined using multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Fifty-three (36.8%) reported a designated FP individual or team. Sperm banking was offered at 135 (97.8%) institutions, and testicular tissue cryopreservation at 37 (27.0%). Oocyte and embryo cryopreservation were offered at 91 (67.9%) and 62 (46.6%) institutions, respectively; ovarian tissue cryopreservation was offered at 64 (47.8%) institutions. The presence of dedicated FP personnel was independently associated with the ability to offer oocyte or embryo cryopreservation (odds ratio [OR], 4.7; 95% CI, 1.7 to 13.5), ovarian tissue cryopreservation (OR, 2.7; 95% CI, 1.2 to 6.0), and testicular tissue cryopreservation (OR, 3.3; 95% CI, 1.4 to 97.8). Only 26 (18.1%) participating institutions offered all current nonexperimental FP interventions. Barriers included cost (70.9%), inadequate knowledge or training (60.7%), difficulty characterizing fertility risk (50.4%), inadequate staffing (45.5%), and logistics with reproductive specialties (38%-39%). CONCLUSION: This study provides the most comprehensive view of the current landscape of FP infrastructure for children and adolescents with cancer and demonstrates that existing infrastructure is inadequate to offer comprehensive services to patients. We discuss modifiable factors to improve patient access to FP.

Parent and Clinician Perspectives on Challenging Parent-Clinician Relationships in Pediatric Oncology.

Importance: Parents of children with cancer value strong therapeutic relationships with oncology clinicians, but not every relationship is positive. Objective: To identify the prevalence of challenging parent-clinician relationships in pediatric oncology and factors associated with these challenges from parent and clinician perspectives. Design, Setting, and Participants: This survey was conducted among parents and oncology clinicians of children with cancer within 3 months of diagnosis from November 2015 to July 2019 at Dana-Farber Cancer Institute/Boston Children's Hospital and Texas Children's Hospital. Participants were 400 parents of children with cancer and 80 clinicians (ie, oncology physicians and nurse practitioners). Parents completed surveys about relationships with 1 to 2 primary oncology clinicians; clinicians completed surveys about relationships with parents. Data were analyzed from July 2020 to August 2021. Exposures: At least 3 previous clinical visits between parent and clinician. Main Outcomes and Measures: The Relationship Challenges Scale Parent Version and Clinician Version were developed and used to measure threats to the therapeutic alliance. For the Relationship Challenges Scale-Parent version, relationships were considered challenging if a parent responded to any single question in the 2 lowest of 4 possible categories. For the Relationship Challenges Scale-Clinician version, challenges were considered to be present if a clinician reported responses in the 3 lowest of 6 possible response categories to any question. Results: Among 400 parents, there were 298 [74.5%] women, 25 Asian individuals (6.3%), 28 Black individuals (7.0%), 97 Hispanic individuals (24.3%), 223 White individuals (55.8%), and 10 individuals (2.4%) with other race or ethnicity; race and ethnicity data were missing for 17 (4.3%) individuals. Among 80 clinicians, there were 57 (71.3%) women, 38 attending physicians (47.5%), 32 fellows (40.0%), and 10 nurse practitioners (12.5%). Parents identified 676 unique relationships with clinicians, and clinician reports were available for 338 relationships. Among 338 relationships with paired parent and clinician surveys, 81 relationships (24.0%) were considered challenging by parents, 127 relationships (37.6%) were considered challenging by clinicians, and 33 relationships (9.8%) were considered challenging by parent and clinician. Parents with Asian or other race or ethnicity (odds ratio [OR] vs White parents, 3.62; 95% CI, 1.59-8.26) or who had lower educational attainment (OR for ≤high school vs >high school, 3.03; 95% CI, 1.56-5.90) were more likely to experience relationships as challenging. Clinicians used a variety of strategies more frequently in 127 relationships in which they perceived challenges vs 211 relationships in which they did not perceive challenges, such as holding regular family meetings (22 relationships [17.3%] vs 13 relationships [6.2%]; P = .009) and offering extra time and attention (66 relationships [52%] vs 60 relationships [28.4%]; P < .001). However, these strategies were not used with increased frequency when parents experienced relationships as challenging vs when parents did not experience this. Conclusions and Relevance: This survey study found that nearly one-quarter of parents of children with cancer reported challenges in the therapeutic relationship with their oncologist and that clinicians used strategies to improve relationships more frequently when they experienced the relationship as challenging. These findings suggest that new strategies are needed to improve experiences for parents and to help clinicians recognize and attend to parents whose experiences are suboptimal.

SARS-CoV-2 in Childhood Cancer in 2020: A Disease of Disparities.

PURPOSE: The Pediatric Oncology COVID-19 Case Report registry supplies pediatric oncologists with data surrounding the clinical course and outcomes in children with cancer and SARS-CoV-2. METHODS: This observational study captured clinical and sociodemographic characteristics for children (≤ 21 years) receiving cancer therapy and infected with SARS-CoV-2 from the pandemic onset through February 19, 2021. The demographic and clinical characteristics of the cohort were compared with population-level pediatric oncology data (SEER). Multivariable binomial regression models evaluated patient characteristics associated with hospitalization, intensive care unit (ICU) admission, and changes in cancer therapy. RESULTS: Ninety-four institutions contributed details on 917 children with cancer and SARS-CoV-2. Median age at SARS-CoV-2 infection was 11 years (range, 0-21 years). Compared with SEER, there was an over-representation of Hispanics (43.6% v 29.7%, P < .01), publicly insured (59.3% v 33.5%, P < .01), and patients with hematologic malignancies (65.8% v 38.3%, P < .01) in our cohort. The majority (64.1%) were symptomatic; 31.2% were hospitalized, 10.9% required respiratory support, 9.2% were admitted to the ICU, and 1.6% died because of SARS-CoV-2. Cancer therapy was modified in 44.9%. Hispanic ethnicity was associated with changes in cancer-directed therapy (adjusted risk ratio [aRR] = 1.3; 95% CI, 1.1 to 1.6]). Presence of comorbidities was associated with hospitalization (aRR = 1.3; 95% CI, 1.1 to 1.6) and ICU admission (aRR = 2.3; 95% CI, 1.5 to 3.6). Hematologic malignancies were associated with hospitalization (aRR = 1.6; 95% CI, 1.3 to 2.1). CONCLUSION: These findings provide critical information for decision making among pediatric oncologists, including inpatient versus outpatient management, cancer therapy modifications, consideration of monoclonal antibody therapy, and counseling families on infection risks in the setting of the SARS-CoV-2 pandemic. The over-representation of Hispanic and publicly insured patients in this national cohort suggests disparities that require attention.

An evidence-based, risk-adapted algorithm for antifungal prophylaxis reduces risk for invasive mold infections in children with hematologic malignancies.

BACKGROUND: Children with hematologic malignancies, especially those who receive intensive chemotherapy, are at high risk for invasive mold infections (IMI) that confer substantial mortality. Randomized controlled trials support the use of antifungal prophylaxis with antimold activity as an optimal strategy for risk reduction in this population, but studies outlining the practical application of evidence-based recommendations are lacking. PROCEDURE: We conducted a 15-year, single-institution retrospective review in a diverse cohort of children with hematologic malignancies treated with chemotherapy to determine the incidence of proven or probable IMI diagnosed between 2006 and 2020. Multivariable logistic regression was used to identify host and disease factors associated with IMI risk. We then compared the incidence and type of IMI and related factors before and after 2016 implementation of an evidence-based, risk-adapted antifungal prophylaxis algorithm that broadened coverage to include molds in patients at highest risk for IMI. RESULTS: We identified 61 cases of proven or probable IMI in 1456 patients diagnosed with hematologic malignancies during the study period (4.2%). Implementation of an antifungal prophylaxis algorithm reduced the IMI incidence in this population from 4.8% to 2.9%. Both Hispanic ethnicity and cancer diagnosis prior to 2016 were associated with risk for IMI. CONCLUSION: An evidence-based, risk-adapted approach to antifungal prophylaxis for children with hematologic malignancies is an effective strategy to reduce incidence of IMI.

Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma.

Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed-Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL. Pre-therapy plasma samples were obtained from pediatric subjects with newly diagnosed HL and healthy pediatric controls. Plasma concentrations of 135 cytokines/chemokines were measured with the Luminex platform. Associations between protein concentration and disease characteristics were determined using multivariate permutation tests with false discovery control. Fifty-six subjects with HL (mean age: 13 years, range 3-18) and 47 controls were analyzed. The cytokine/chemokine profiles of subjects with HL were distinct from controls, and unique cytokines/chemokines were associated with high-risk disease (IL-10, TNF-α, IFN-γ, IL-8) and slow early response (CCL13, IFN-λ1, IL-8). TNFSF10 was significantly elevated among those who ultimately relapsed and was significantly associated with worse event-free survival. These biomarkers could be incorporated into biologically based risk stratification to optimize outcomes and minimize toxicities in pediatric HL.