Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute.Fil: Mukkada, Sheena. St Jude Children's Research Hospital; Estados UnidosFil: Bhakta, Nickhill. St Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Hospital Sant Joan de Déu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chen, Yichen. St Jude Children's Research Hospital; Estados UnidosFil: Vedaraju, Yuvanesh. St Jude Children's Research Hospital; Estados UnidosFil: Faughnan, Lane. St Jude Children's Research Hospital; Estados UnidosFil: Homsi, Maysam R. St Jude Children's Research Hospital; Estados UnidosFil: Muniz Talavera, Hilmarie. St Jude Children's Research Hospital; Estados UnidosFil: Ranadive, Radhikesh. St Jude Children's Research Hospital; Estados UnidosFil: Metzger, Monika. St Jude Children's Research Hospital; Estados UnidosFil: Friedrich, Paola. St Jude Children's Research Hospital; Estados UnidosFil: Agulnik, Asya. St Jude Children's Research Hospital; Estados UnidosFil: Jeha, Sima. St Jude Children's Research Hospital; Estados UnidosFil: Lam, Catherine G.. St Jude Children's Research Hospital; Estados UnidosFil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; IndiaFil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de ÁfricaFil: Moreira, Daniela. St Jude Children's Research Hospital; Estados UnidosFil: Santana, Victor M. St Jude Children's Research Hospital; Estados UnidosFil: Sullivan, Michael. University of Melbourne; AustraliaFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; CanadáFil: Caniza, Miguela A.. St Jude Children's Research Hospital; Estados UnidosFil: Devidas, Meenakshi. St Jude Children's Research Hospital; Estados UnidosFil: Pritchard Jones, Kathy. UCL Great Ormond Street Institute of Child Health; Reino UnidoFil: Rodriguez Galindo, Carlos. St Jude Children's Research Hospital; Estados Unido

The Global COVID-19 Observatory and Resource Center for Childhood Cancer: A response for the pediatric oncology community by SIOP and St. Jude Global

The COVID-19 pandemic quickly led to an abundance of publications and recommendations, despite a paucity of information on how COVID-19 affects children with cancer. This created a dire need for a trusted resource with curated information and a space for the pediatric oncology community to share experiences. The Global COVID-19 Observatory and Resource Center for Childhood Cancer was developed, launched, and maintained by the International Society of Pediatric Oncology and St. Jude Children's Research Hospital. The three components (Resource Library, Global Registry, and Collaboration Space) complement each other, establishing a mechanism to generate and transfer knowledge rapidly throughout the community.Fil: Moreira, Daniel C.. St. Jude Children's Research Hospital; Estados UnidosFil: Sniderman, Elizabeth. St. Jude Children's Research Hospital; Estados UnidosFil: Mukkada, Sheena. St. Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Bhakta, Nickhill. St. Jude Children's Research Hospital; Estados UnidosFil: Foster, Whitney. St. Jude Children's Research Hospital; Estados UnidosFil: Avula, Meghana. St. Jude Children's Research Hospital; Estados UnidosFil: Homsi, Maysam R.. St. Jude Children's Research Hospital; Estados UnidosFil: Faughnan, Lane. St. Jude Children's Research Hospital; Estados UnidosFil: Happ, Brooke. St. Jude Children's Research Hospital; Estados UnidosFil: Andujar, Allyson. St. Jude Children's Research Hospital; Estados UnidosFil: Sonnenfelt, Jason. St. Jude Children's Research Hospital; Estados UnidosFil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; IndiaFil: Frazier, A. Lindsay. No especifíca;Fil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de ÁfricaFil: Kearns, Pamela R.. No especifíca;Fil: Luna Fineman, Sandra. No especifíca;Fil: Moreno, Arturo. Hospital Universitario de Puebla; MéxicoFil: Saghir Khan, Muhammad. No especifíca;Fil: Sullivan, Michael. Royal Children's Hospital, Melbourne; AustraliaFil: Devidas, Meenakshi. St. Jude Children's Research Hospital; Estados UnidosFil: Santana, Victor. St. Jude Children's Research Hospital; Estados UnidosFil: Caniza, Miguela. St. Jude Children's Research Hospital; Estados UnidosFil: Pritchard Jones, Kathy. University College London; Estados UnidosFil: Rodriguez Galindo, Carlos. St. Jude Children's Research Hospital; Estados Unido

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute.Fil: Mukkada, Sheena. St Jude Children's Research Hospital; Estados UnidosFil: Bhakta, Nickhill. St Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Hospital Sant Joan de Déu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chen, Yichen. St Jude Children's Research Hospital; Estados UnidosFil: Vedaraju, Yuvanesh. St Jude Children's Research Hospital; Estados UnidosFil: Faughnan, Lane. St Jude Children's Research Hospital; Estados UnidosFil: Homsi, Maysam R. St Jude Children's Research Hospital; Estados UnidosFil: Muniz Talavera, Hilmarie. St Jude Children's Research Hospital; Estados UnidosFil: Ranadive, Radhikesh. St Jude Children's Research Hospital; Estados UnidosFil: Metzger, Monika. St Jude Children's Research Hospital; Estados UnidosFil: Friedrich, Paola. St Jude Children's Research Hospital; Estados UnidosFil: Agulnik, Asya. St Jude Children's Research Hospital; Estados UnidosFil: Jeha, Sima. St Jude Children's Research Hospital; Estados UnidosFil: Lam, Catherine G.. St Jude Children's Research Hospital; Estados UnidosFil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; IndiaFil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de ÁfricaFil: Moreira, Daniela. St Jude Children's Research Hospital; Estados UnidosFil: Santana, Victor M. St Jude Children's Research Hospital; Estados UnidosFil: Sullivan, Michael. University of Melbourne; AustraliaFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; CanadáFil: Caniza, Miguela A.. St Jude Children's Research Hospital; Estados UnidosFil: Devidas, Meenakshi. St Jude Children's Research Hospital; Estados UnidosFil: Pritchard Jones, Kathy. UCL Great Ormond Street Institute of Child Health; Reino UnidoFil: Rodriguez Galindo, Carlos. St Jude Children's Research Hospital; Estados Unido

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients

Background and aimsPediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico.MethodsPatients &lt;18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined.ResultsOverall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1–10 years, with DNA index &gt;0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS.ConclusionOutcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes

Prospective randomized crossover evaluation of three anesthetic regimens for painful procedures in children with cancer

Objective: To identify the most effective sedation regimen for bone marrow aspiration and lumbar puncture procedures with a prospective trial of 3 combinations of sedation/analgesia. Study design: In this double-blind crossover study, we randomly assigned 162 children with acute lymphoblastic leukemia or lymphoblastic lymphoma to receive fentanyl 1 mcg/kg, fentanyl 0.5 mcg/kg, or placebo, in addition to propofol and topical anesthetic for 355 procedures. Results: We found no significant differences among the 3 regimens in the frequency of pain (pain score \u3e 0) or severe pain (pain score ≥ 5) during recovery, or a \u3e20% increase in hemodynamic/respiratory variables during anesthesia. Treatment with fentanyl 1 mcg/kg was associated with a lower frequency of movement during procedure compared with treatment with fentanyl 0.5 mcg/kg (P =.0476) or treatment with placebo (P =.0545). The placebo group required longer time to recover (median, 18 minutes) compared with the fentanyl 0.5 mcg/kg group (median, 9 minutes) (median difference 2.0, P =.007) and the fentanyl 1 mcg/kg (median 8 minutes), (median difference 2.0, P =.15). The placebo group also required larger total dose of propofol (median 5 mg/kg) compared with that of the fentanyl 1 mcg/kg group (median, 3.5 mg/kg) and the fentanyl 0.5 mcg/kg group (median 3.5 mg/kg) (median differences 1.5, P \u3c.00005, in both comparisons). Conclusion: The addition of fentanyl 1 mcg/kg to propofol for brief painful procedures reduces movement, propofol dose, and recovery time. Copyright © 2013 Mosby Inc

Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study

Background/aims: Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. Methods: In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical. Results: In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff. Lessons learned: Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures whenever possible. Conclusion: This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies