Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 ...in patients followed in French pediatric oncology and hematology wards. All patients diagnosed with COVID-19 and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Data were available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Children and young adults treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored.
Primary infection with varicella-zoster virus (VZV) causes chickenpox, a benign and self-limited disease in healthy children. In patients with primary or acquired immunodeficiencies, primary ...infection can be life-threatening, due to rapid dissemination of the virus to various organs lung, gastrointestinal tract, liver, eye, central nervous system (CNS). We retrospectively described and compared the clinical presentations and outcomes of disseminated varicella infection (DV) in patients with acquired (AID) (
= 7) and primary (PID) (
= 12) immunodeficiencies. Patients with AID were on immunosuppression (mostly steroids) for nephrotic syndrome, solid organ transplantation or the treatment of hemopathies, whereas those with PID had combined immunodeficiency (CID) or severe CID (SCID). The course of the disease was severe and fulminant in patients with AID, with multiple organ failure, no rash or a delayed rash, whereas patients with CID and SICD presented typical signs of chickenpox, including a rash, with dissemination to other organs, including the lungs and CNS. In the PID group, antiviral treatment was prolonged until immune reconstitution after bone marrow transplantation, which was performed in 10/12 patients. Four patients died, and three experienced neurological sequelae. SCID patients had the worst outcome. Our findings highlight substantial differences in the clinical presentation and course of DV between children with AID and PID, suggesting differences in pathophysiology. Prevention, early diagnosis and treatment are required to improve outcome.
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.
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.
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).
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.
American Lebanese Syrian Associated Charities and the National Cancer Institute.
To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had ...undergone allogeneic hematopoietic stem cell transplantation (a-HSCT).
We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units.
From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with “emergent” fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P < .0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10−4) compared with a-HSCT recipients who did not receive antifungal prophylaxis. The main cause of IFI in children receiving prophylaxis was emergent pathogens (41%), such as mucormycosis and fusariosis, which were resistant to the prophylactic agents.
The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.
Background:
In developed countries, cancer remains the leading cause of pediatric death from illness after the neonatal period.
Objective:
To describe the end-of-life care characteristics of children ...and adolescents with solid tumors (ST) or hematologic malignancies (HM) who died from tumor progression in the Île-de-France area.
Methods:
This is a regional, multicentric, retrospective review of medical files of all children and adolescents with cancer who died over a 1-year period. Extensive data from the last 3 months of life were collected.
Results:
A total of 99 eligible patients died at a median age of 9.8 years (range, 0.3–24 years). The most frequent terminal symptoms were pain (n = 86), fatigue (n = 84), dyspnea (n = 49), and anorexia (n = 41). Median number of medications per patient was 8 (range, 3–18). Patients required administration of opioids (n = 91), oxygen (n = 36), and/or sedation (n = 61). Decision for palliative care was present in all medical records and do-not-resuscitate orders in 90/99 cases. Symptom prevalence was comparable between children and adolescents with ST and HM. A wish regarding the place of death had been expressed for 64 patients and could be respected in 42 cases. Death occurred in hospital for 75 patients.
Conclusions:
This study represents a large and informative cohort illustrating current pediatric palliative care approaches in pediatric oncology. End-of-life remains an active period of care requiring coordination of multiple care teams.
Abstract
PCR-based methods applied to various body fluids emerged in recent years as a promising approach for the diagnosis of mucormycosis. In this study, we set up and assess the value of a qPCR to ...detect a wide variety of Mucorales species in a single tube. A pair of degenerated primers targeting the rDNA operon was used in a qPCR utilizing an intercalating fluorescent dye. Analytical assessment, using a wide variety of both Mucorales strains (8 genera, 11 species) and non-Mucorales strains (9 genera, 14 species), showed 100% sensitivity and specificity rates with a limit of detection at 3 rDNA copy/qPCR reaction. Subsequently, 364 clinical specimens from 166 at-risk patients were prospectively tested with the assay. All the seven patients classified as proven/probable mucormycosis using the EORTC-MSG criteria had a positive qPCR as well as a patient with a proven uncharacterized invasive mold infection. In addition, three out of seven patients with possible mold invasive infections had at least one positive qPCR test. Sensitivity was calculated between 73.33 and 100% and specificity between 98.10 and 100%. The qPCR method proposed showed excellent performances and would be an important adjunctive tool for the difficult diagnosis of mucormycosis diagnosis.
Lay abstract
qPCR-based diagnosis is the most reliable approach for mucormycosis. We set up a pan-Mucorales qPCR able to detect in a single reaction not less than 11 different species. Both analytical and clinical performances support its use in the clinical setting.
Abstract Fusarium spp. are plant pathogens and opportunistic pathogens in severely immunocompromised (hematological malignancy, neutropenia, solid organ transplantation, etc.) and severely burned ...patients. Invasive fusariosis often disseminates and mortality remains high partly due to delayed diagnosis in the absence of a positive culture. The aim of our study is to design a quantitative PCR (qPCR) assay and evaluate the detection of Fusarium spp. DNA for early diagnosis of invasive infection. A qPCR assay was designed and optimized to identify all Fusarium species complex and secondarily evaluated on patient samples. A total of 81 blood samples from 15 patients diagnosed with proven invasive fusariosis from 9 centers in France were retrospectively tested. Circulating DNA was detected in 14 patients out of 15 (sensitivity of 93% 95% Confidence Interval (CI95), 70.1-99.7). Detection was possible up to 18 days (median 6 days) before the diagnosis was confirmed by positive blood culture or biopsy. By comparison serum galactomannan and ß-D-glucan were positive in 7.1 and 58.3% of patients respectively. qPCR was negative for all patients with other invasive fungal diseases (IFD) tested (n = 12) and IFD-free control patients (n = 40). No cross-reactions were detected using DNA extracted from 81 other opportunistic fungi. We developed and validated a pan-Fusarium qPCR assay in serum/plasma with high sensitivity, specificity, and reproducibility that could facilitate early diagnosis and treatment monitoring of invasive fusariosis. Lay Abstract Fusariosis ranks third among invasive mould infections. It is frequently diagnosed late due to the lack of specific tools. We designed and evaluated a new qPCR assay with high sensitivity and specificity allowing detection of Fusarium DNA in serum samples up to 18 days before conventional diagnosis.
Les microsporidioses intestinales sont des infections sous-estimées affectant à la fois les patients immunodéprimés et immunocompétents. Le diagnostic microscopique en laboratoire médical est aujourd’hui supplanté par la PCR en temps réel. Cependant, peu de fabricants incluent les microsporidies dans leurs panels PCR pour le diagnostic des gastro-entérites infectieuses. Ici, nous avons évalué les performances des tests PCR en temps réel microsporidia generic et microsporidia typing (Bio-Evolution, France) sur le thermocycleur PCR en temps réel Rotor-Gene Q (Qiagen, France). Nous avons inclus 45 échantillons de selles négatifs et 44 échantillons positifs pour Enterocytozoon bieneusi ( n = 34, avec divers génotypes), Encephalitozoon intestinalis ( n = 4), Encephalitozoon hellem ( n = 4) et Encephalitozoon cuniculi ( n = 2). Nous avons également analysé les résultats sur 4 ans d’un programme de contrôle qualité inter-laboratoires dont 9 centres ont utilisé ces kits commerciaux. La sensibilité et la spécificité du kit microsporidia generic étaient respectivement de 86,4 % et 93,3 %. Encephalitozoon hellem et E. cuniculi ont été détectés par le kit microsporidia generic mais pas par le kit microsporidia typing. Ces résultats étaient cohérents avec ceux du programme de contrôle de qualité inter-laboratoires. En conclusion, les tests de PCR en temps réel Bio-Evolution sont des outils intéressants pour la microsporidiose intestinale, mais un résultat négatif pour le test de typage microsporidia nécessite une analyse supplémentaire pour confirmer les infections à E. hellem ou E. cuniculi .
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Introduction: Thrombopoietin receptor agonist eltrombopag (ELT) provides hematologic improvement in up to 50% of adults with acquired aplastic anemia (AAA) refractory to immunosuppressive therapy ...(IST). However, current data for ELT efficacy and tolerance in childhood AAA is very limited.
Methods: We conducted a multicenter nationwide retrospective study on behalf of the French Reference Center for Aplastic Anemia. Patients under 18 treated with ELT after IST for AAA were included. Lineage responses were defined as follows: red cells transfusion independency or hemoglobin increase of 1.5 g/dL, platelets transfusion independency or a 20 G/L increase in platelets counts, doubling of the neutrophil count or an increase above 0.5 G / L.
Results: We identified 12 children (2-17 years old, mean 9.5±5.9 years) treated for severe (7) /very severe (5) AAA with horse ATG and cyclosporine as first-line treatment between 2014 and 2018 in five different centers. Minor PNH clone was identified at diagnosis in two patients. All patients had a normal bone-marrow karyotype and FISH. None had a matched related donor. Median time between IST onset and eltrombopag initiation was 3.5 months 1-46. All patients still met severe aplastic anemia criteria and needed RBC and platelet transfusions at ELT initiation. Mean hemoglobin, reticulocytes, platelets and neutrophils values were 7.3±0.8 g/dL, 24.5±24 G/L, 11±5.9 G/L and 0.8±0.7 G/L. Seven patients had received IST for more than 3 months and were therefore considered refractory to this treatment. ELT was indicated for an uncontrolled bacterial infection in 2 patients one and two months after IST initiation. One patient received an excessive dose of 12.5 mg/kg/day. Average ELT dosage for the other patients was 2±0.6 mg/kg/d. The median duration of treatment with ELT was 5.5 months 1-10. After ELT initiation, nine patients (75%) reached hematological response for at least one cell line with no additional treatment. In these patients, hemoglobin increased on average by 3±1.3 g/dL, neutrophils by 2.5±3.5 G/L and platelets by 89.8±39.7 G/L. Seven patients (58%) achieved a trilineage response and were both RBC and platelets transfusions independent after 1 month (1), 3 months (3) and six months (7). Five patients (41.6%) reached a robust response (platelets > 50 G/L, hemoglobin > 10 g/dL, neutrophils > 1 G/L). All these trilineage responders were still on cyclosporine at the time of last assessment. ELT was withdrawn in 4 trilineage responders. Two of them still fulfilled robust response criteria 3 and 43 months after ELT withdrawal while the 2 others required occasional transfusions. The 3 others trilineage responders who were still receiving ELT remained transfusion independent 6 (2) and 11 (1) months after ELT initiation. Two patients (16.6%) had a unique lineage response: one was lost of view and one developed a myelodysplasia with RUNX1 mutation 3 months after ELT initiation. He is alive 8 months after HSCT. No clonal evolution was reported in the 5 other patients for whom cytogenetics follow-up was available. No response was achieved in 3 patients (25%), all of whom were treated for less than 3 months: ELT was withdrawn for deemed inefficiency in 2 patients (16.6%) after 1 and 2 months respectively and for toxicity (disseminated intravascular coagulation) in another patient after 2 months. These patients underwent HSCT. One patient died of graft failure 3 months after HSCT. Overall, eleven patients (91%) were alive 13.4±5.6 months after eltrombopag onset. Disseminated intravascular coagulation occurred in a 2 years patient who received a large ELT dosage (12.5 mg/Kg). No other grade III-IV toxicity was reported.
Discussion/Conclusion: This is the first report of ELT for childhood severe AAA after IST. Eltrombopag was overall well tolerated. We observed a high rate of sustained trilineage response as reported in adult patients and only 1 case of clonal evolution which is a known complication in non-responsive AAA. Onset of the trilinear hematologic responses is progressive and achieved 3-6 months after ELT initiation. A longer follow-up of this cohort is mandatory to assess response durability and clonal evolution final risk. Nevertheless, we propose that ELT should be considered for severe AAA non-responsive to IST after 3 months of treatment especially if only an alternative donor is available.
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No relevant conflicts of interest to declare.
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