ABSTRACT
INTRODUCTION: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. METHODS: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. RESULTS: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1). CONCLUSIONS: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.
Subject(s)
COVID-19 , Down Syndrome , Hematologic Neoplasms , Hospitalization , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hematologic Neoplasms/complications , Adolescent , Male , Down Syndrome/complications , Down Syndrome/epidemiology , Female , Child , Young Adult , Hospitalization/statistics & numerical data , Adult , Child, Preschool , InfantABSTRACT
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.
Subject(s)
Neoplasms , Quality of Life , Adolescent , Young Adult , Child , Humans , Neoplasms/drug therapy , Medical Oncology , Delivery of Health Care , VomitingABSTRACT
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.
Subject(s)
Hepatic Veno-Occlusive Disease , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Male , Child , Humans , Mercaptopurine , Hepatic Veno-Occlusive Disease/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Thioguanine/adverse effects , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/complications , T-LymphocytesABSTRACT
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.
Subject(s)
Bacteremia , Clostridioides difficile , Cross Infection , Leukemia, Myeloid, Acute , Sepsis , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Bacteremia/epidemiology , Bacteremia/etiology , Bacteremia/prevention & control , Child , Cross Infection/epidemiology , Cross Infection/prevention & control , Delivery of Health Care , Diarrhea/chemically induced , Diarrhea/epidemiology , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/drug therapy , Levofloxacin/therapeutic use , Retrospective Studies , Sepsis/complicationsABSTRACT
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.
Subject(s)
Antineoplastic Agents , Cardiomyopathies , Heart Failure , Heart Transplantation , Heart-Assist Devices , Antineoplastic Agents/adverse effects , Cardiomyopathies/chemically induced , Cardiomyopathies/therapy , Child , Heart Failure/etiology , Heart Transplantation/adverse effects , Heart-Assist Devices/adverse effects , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Hematologic Neoplasms , Mycoses , Algorithms , Antifungal Agents/therapeutic use , Child , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Humans , Mycoses/etiology , Mycoses/prevention & control , Retrospective StudiesABSTRACT
Skewing of mercaptopurine (6-MP) metabolism preferentially toward the 6-methylmercaptopurine (6-MMP) metabolite over the antileukemic metabolite 6-thioguanine (6-TGN) is associated with 6-MP-related hepatotoxocity. Allopurinol when coadministered with 6-MP can reduce this skewing and ameliorate the associated adverse effects. The cases we report here demonstrate that aberrant overproduction of 6-MMP is also associated with profound 6-MP-associated hypoglycemia, which can be reversed by administration of allopurinol. This case series contributes to the scant literature on 6-MP-induced hypoglycemia and provides evidence that addition of allopurinol to reduced dose 6-MP can successfully manage this severe toxicity.
Subject(s)
Hypoglycemia , Mercaptopurine , Thioguanine/metabolism , Allopurinol/administration & dosage , Allopurinol/pharmacokinetics , Child , Female , Humans , Hypoglycemia/blood , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Male , Mercaptopurine/administration & dosage , Mercaptopurine/adverse effects , Mercaptopurine/pharmacokineticsABSTRACT
Attendance to follow-up care after completion of cancer treatment is an understudied area. We examined demographic, clinical, and socioeconomic predictors of follow-up by pediatric cancer patients at a large center in 442 newly diagnosed patients using multivariable logistic regression analyses. Patients who did not return to clinic for at least 1000 days were considered lost to follow-up. Two hundred forty-two (54.8%) patients were lost. In multivariable analyses, the following variables were independent predictors of being lost to follow-up: treatment with surgery alone (odds ratio [OR]=6.7; 95% confidence interval [CI], 3.1-14.9), older age at diagnosis (reference, 0 to 4; ages, 5 to 9: OR=1.8, 95% CI, 1.1-3; ages, 10 to 14: OR=3.3; CI, 1.8-6.1; and ages, 15 and above: OR=4.8; CI, 2.1-11.7), lack of history of stem cell transplantation (OR=2, 95% CI, 1.04-3.7) and lack of insurance (OR=3.4; CI, 1.2-9.2). Hispanic patients had the best follow-up rates (53.7%) compared to whites and blacks (P=0.03). Attendance to long-term follow-up care is suboptimal in childhood cancer survivors. Predictors that were associated with nonattendance can be used to design targeted interventions to improve follow-up care for survivors of pediatric cancer.
Subject(s)
Aftercare/standards , Neoplasms/therapy , Patient Acceptance of Health Care/statistics & numerical data , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Multivariate Analysis , Patient Acceptance of Health Care/ethnology , Patient Compliance/ethnology , Patient Compliance/statistics & numerical data , Risk Factors , SurvivorsABSTRACT
Mercaptopurine (6-MP), a critical component of acute lymphoblastic leukemia (ALL) therapy, is metabolized to 6-thioguanine (6-TGN) which is responsible for its anti-leukemic effect, and to 6-methylmercaptopurine nucleotides (6-MMPN/6-MMP) which can be hepatotoxic. Some patients preferentially metabolize 6-MP to 6-MMPN which may increase the risk of liver injury, reduce serum levels of 6-TGN and potentially increase the risk of relapse. The addition of allopurinol to oral 6-MP has been shown to optimize metabolism towards 6-TGN in patients with inflammatory bowel disease (IBD); however, this use has not been reported in patients undergoing treatment for ALL.
Subject(s)
Allopurinol/therapeutic use , Antimetabolites, Antineoplastic/pharmacokinetics , Mercaptopurine/analogs & derivatives , Mercaptopurine/pharmacokinetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Allopurinol/pharmacology , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biotransformation/drug effects , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Child, Preschool , Drug Evaluation , Female , Guanine Nucleotides/blood , Humans , Hyperbilirubinemia/chemically induced , Hypoxanthine Phosphoribosyltransferase/metabolism , Maintenance Chemotherapy , Male , Mercaptopurine/administration & dosage , Mercaptopurine/adverse effects , Mercaptopurine/blood , Methotrexate/administration & dosage , Methyltransferases/metabolism , Neutropenia/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Thionucleotides/blood , Xanthine Oxidase/metabolismABSTRACT
Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.
ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Fever , Neoplasms , Humans , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Child , Fever/drug therapy , Neoplasms/complications , Neoplasms/drug therapy , Female , Male , Child, Preschool , Adolescent , Time-to-TreatmentABSTRACT
PURPOSE: Unlike most childhood cancers, therapy for ALL includes a prolonged maintenance phase during which children typically resume regular activities. Physicians need data regarding the persistent impact of COVID-19 in this population to help guide families after the pandemic. METHODS: The Pediatric Oncology COVID-19 Case Report (POCC) collects deidentified data (sociodemographics, clinical data [cancer, COVID-19 course]) on children, adolescents, and young adults with cancer and COVID-19 from 104 US pediatric oncology institutions. The analysis presented here compares children (≤21 years) with ALL in maintenance (ALL-MTN) with all other children with cancer and COVID-19. Multivariable analyses adjust for age, race/ethnicity, insurance, absolute neutrophil count at the time of infection, vaccination, and comorbidities. RESULTS: Compared with other children reported to POCC (n = 1,190), those in ALL-MTN (n = 481) were less often hospitalized (23% v 29%, P = .01) or admitted to the intensive care unit (ICU: 3% v 5%, P = .01); these findings persisted in multivariable analysis (hospitalization: odds ratio [OR], 0.7 [95% CI, 0.6 to 0.9]; ICU: OR, 0.5 [95% CI, 0.2 to 0.8]). However, cancer-directed therapy was changed more often for children in ALL-MTN (50% v 33%, P ≤ .01; OR, 2.0 [95% CI, 1.6 to 2.5[). Vaccination was an independent prognostic factor in our multivariable model, decreasing odds of hospitalization (OR, 0.7 [95% CI, 0.5 to 0.9]). CONCLUSION: Children in ALL-MTN required fewer hospitalizations and ICU admissions but more therapy modifications than other children with cancer. Vaccination against COVID-19 reduced the odds of hospitalization.
ABSTRACT
Adolescents and young adults (ie, individuals aged 15-39 years, known as AYAs) with cancer face unique vulnerabilities yet remain underrepresented in clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8%-12%). We used the Pediatric Oncology COVID-19 Case Report to examine the clinical course of COVID-19 among AYAs with cancer. The Pediatric Oncology COVID-19 Case Report collects deidentified clinical and sociodemographic data regarding individuals aged from birth to 39 years with cancer (37%) and COVID-19 from more than 100 institutions. Between April 1, 2020, and November 28, 2023, 191 older AYAs (individuals 22-39 years of age) and 640 younger AYAs (individuals 15-21 years of age) were captured. Older AYAs were less often hospitalized (P < .001), admitted to the intensive care unit (P = .02), and required respiratory support (P = .057). In multivariable analyses, older AYAs faced 80% lower odds of intensive care unit admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of intensive care unit admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform oncology teams directing COVID-19 management and prevention in AYA patients with cancer.
Subject(s)
COVID-19 , Neoplasms , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , COVID-19/therapy , Adolescent , Neoplasms/epidemiology , Neoplasms/therapy , Young Adult , Male , Female , Adult , SARS-CoV-2/isolation & purification , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Age FactorsABSTRACT
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.
Subject(s)
Fertility Preservation , Neoplasms , Adolescent , Young Adult , Humans , Male , Female , Child , United States , Cross-Sectional Studies , Semen , Medical Oncology , Neoplasms/complications , Neoplasms/therapyABSTRACT
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).
Subject(s)
COVID-19 , Neoplasms , Child , Humans , Adolescent , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , SARS-CoV-2 , Cohort Studies , Risk Factors , Neoplasms/epidemiology , Neoplasms/therapy , Disease ProgressionABSTRACT
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.
ABSTRACT
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.
Subject(s)
Clinical Trials as Topic , Neoplasms , Patient Reported Outcome Measures , Adolescent , Humans , Young Adult , Neoplasms/drug therapy , Quality of Life , Adult , Healthcare Disparities , Antineoplastic Agents/toxicityABSTRACT
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.