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Competing Interests: The authors declare no conflict of interest.

Objective: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Study Design: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Sick Children Reference Centre., Results: We identified 19 children who had a history of SARS-CoV-2 infection and manifest a variety of CNS inflammatory diseases: encephalopathy, cerebellar ataxia, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, or optic neuritis. All patients had a history of SARS-CoV-2 exposure, and all tested positive for circulating antibodies against SARS-CoV-2. At the onset of the neurologic disease, SARS-CoV-2 PCR results (nasopharyngeal swabs) were positive in 8 children. Cerebrospinal fluid was abnormal in 58% (11/19) and magnetic resonance imaging was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (myelin-oligodendrocyte and aquaporin 4 antibodies), representing 21% of the cases. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children. Overall, 89% of patients (17/19) received anti-inflammatory treatment, primarily high-pulse methylprednisolone. All patients had a complete long-term recovery and, to date, no patient with autoantibodies presented with a relapse., Conclusions: SARS2-CoV-2 represents a new trigger of postinfectious CNS inflammatory diseases in children., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The aim is to study statural growth in a large cohort of children with chronic myeloid leukaemia (CML) treated with front-line imatinib., Methods: Retrospective data from 81 children less than 18 years of age with CML identified in the French pediatric registry were analysed. Height was expressed as standard deviation score (SDS)., Results: A gradual decrease in height SDS was observed over time since starting imatinib. The height SDS was significantly lower 12 months and 24 months after the start of imatinib overall (p < 10(-4)) irrespective of gender and pubertal age. The height SDS was significantly (p < 10(-4)) lower 12 months after the start of imatinib in boys and girls, and in the prepubertal age group as well as in the postpubertal age group, respectively. A similar finding was observed in the subgroups of boys and girls starting imatinib at a prepubertal or postpubertal age. Loss in height SDS 12 months after the start of imatinib was of the same range in boys when compared to girls and in patients who started imatinib at a prepubertal age compared to those who started at a postpubertal age., Conclusion: Growth velocity was altered during the first years of imatinib treatment in boys as well as in girls and in prepubertal age patients as well as in adolescents.

Inborn errors of cobalamin (Cbl, vitamin B(12)) absorption include hereditary intrinsic factor deficiency (HIFD) and Imerslund-Gräsbeck disease (IGD). HIFD is secondary to mutations in the HIF gene while IGD is due to mutations in one of the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or amnionless (AMN). These disorders lead to intracellular Cbl depletion which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid (MMA), and methionine depletion. The clinical presentation reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia. Mixed proteinuria, when it is present is strongly suggestive of IGD. Accurate diagnosis is always an emergency because early detection and treatment with life-long parenteral pharmacological doses of hydroxocobalamin are life saving and prevent further deterioration. However, the optimal frequency for cobalamin injections as a maintenance therapy is poorly reported. In order to evaluate the optimal maintenance schedule of cobalamin injections, we retrospectively collected clinical, biological, molecular and treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike previous recommendations, we showed that a maintenance dosage of 1 mg cobalamin twice a year was enough to ensure a normal clinical status and keep the hematological and metabolic parameters in the normal range. These data suggest that patients affected with inborn errors of cobalamin absorption may be safely long-term treated with cobalamin injections every 6 months with careful follow-up of hematological and metabolic parameters. This maintenance regime is beneficial because the patients' quality of life improves., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP., Patients and Methods: A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m(2). Progression-free survival, responses, and tolerance were evaluated., Results: With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events., Conclusion: Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.

Purpose: The objectives of this study were to characterize the population pharmacokinetics of MTX in patients with acute lymphoblastic leukemia (ALL) with ages ranging from 2 to 16 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters., Methods: Seventy-nine children were enrolled in this study; they received 1-4 courses of chemotherapy. MTX was administered at a dose of 5 g/m2. MTX population parameters were estimated from 61 patients (231 courses; age range: 2-16 years). The data were analyzed by nonlinear mixed-effect modeling with use of a two-compartment structural model. The interoccasion variability was taken into account in the model. Eighteen additional patients (70 courses) were used to evaluate the predictive performances of the Bayesian approach and to devise a limited sampling strategy., Results: The following population parameters were obtained: total clearance (CL) = 8.8 l/h (inter-individual variability: 43%), initial volume of distribution (V1) = 17.3 l (48%), k12 = 0.0225 h(-1) (41%), and k21 = 0.0629 h(-1) (24%). The inter-individual variability in the initial volume of distribution was partially explained by the fact that this parameter was weight-dependent. Intercourse variability was limited, with a mean variation of 13.2%. The protocol involving two sampling times, 24 and 48 h after the beginning of infusion, allows precise and accurate determination of individual pharmacokinetic parameters and consequently, it was possible to predict the time at which the MTX concentration reached the predicted threshold (0.2 microM) below which the administration of folinic acid could be stopped., Conclusion: The results of this study combine the relationships between the pharmacokinetic parameters of MTX and patient covariates that may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing pediatric patient care.