Background
X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the
CYBB
gene (located on Xp21.1). Patients with large deletions on chromosome Xp21.1 can ...present with the McLeod phenotype and also Duchenne muscular dystrophy or retinitis pigmentosa. The objective of the present study was to describe a series of French patients with CGD and the McLeod phenotype.
Methods
We retrospectively collected data from the medical records of 8 patients with CGD and the McLeod phenotype registered at the French National Reference Center for blood types.
Results
The median age at diagnosis of CGD was 1.2 years, the median age at diagnosis of the McLeod phenotype was 4.5 years, and the median length of follow-up was 15.2 years. Four patients displayed allo-immunization, with anti-KEL20 and anti-XK1 (formerly known as anti-KL) antibodies. Five of the 6 patients with available blood smears had acanthocytosis. Neuropsychiatric, muscle-related, and ocular manifestations were present in 4, 2, and 1 of the patients, respectively. Three of the 4 patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT) are alive. Overall, 5 patients are alive, and 3 are alive and well.
Conclusion
This is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients.
Juvenile myelomonocytic leukemia (JMML) is a rare, generally aggressive myeloproliferative neoplasm affecting young children. It is characterized by granulomonocytic expansion, with monocytosis ...infiltrating peripheral tissues. JMML is initiated by mutations upregulating RAS signaling. Approximately 10% of cases remain without an identified driver event. Exome sequencing of 2 unrelated cases of familial JMML of unknown genetics and analysis of the French JMML cohort identified 11 patients with variants in SH2B3, encoding LNK, a negative regulator of the JAK-STAT pathway. All variants were absent from healthy population databases, and mutation spectrum was consistent with a loss of function of the LNK protein. A stoploss variant was shown to affect both protein synthesis and stability. The other variants were either truncating or missense, the latter affecting the SH2 domain that interacts with activated JAK. Of the 11 patients, 8 from 5 families inherited pathogenic bi-allelic SH2B3 germline variants from their unaffected heterozygous parents. These children represent half of the cases with no identified causal mutation in the French cohort. They displayed typical clinical and hematological JMML features with neonatal onset and marked thrombocytopenia. They were characterized by absence of additional genetic alterations and a hypomethylated DNA profile with fetal characteristics. All patients showed partial or complete spontaneous clinical resolution. However, progression to thrombocythemia and immunity-related pathologies may be of concern later in life. Bi-allelic SH2B3 germline mutations thus define a new condition predisposing to a JMML-like disorder, suggesting that the JAK pathway deregulation is capable of initiating JMML, and opening new therapeutic options.
The large number of drugs administered simultaneously to neonates and children in hospital results in the formation of particles that are potentially infused. We have investigated the ability of IV ...in-line filters to eliminate particulate matter from multidrug infusion lines and so prevent contamination. The impact on particle occurrence of the internal volume of the IV line below the in-line filter was then evaluated. The multidrug therapy given to children was reproduced with and without in-line filtration. Three combinations with a filter were tested to vary the internal volume (V) between the filter and the catheter egress. The catheter was then connected to a dynamic particle count to evaluate the particulate matter potentially administered to children during infusion. The introduction of in-line filters led to a significant reduction in overall particulate matter, from 416,974 208,479-880,229 to 7,551 1,985-11,287 particles (p < 0.001). Larger particles of ≥10 and 25 µm were also significantly reduced. Adding an extension set to the egress of the in-line filter (V = 1.7 mL) caused a significant increase in particulate contamination for both. This study showed that in-line filtration is an effective tool in preventing particle administration to patients. Their position in the infusion in-line is therefore important because of its impact on internal volume and drug particle formation.
Pediatric chronic immune thrombocytopenia (cITP) is a heterogeneous condition in terms of bleeding severity, second‐line treatment use, association with clinical and/or biological immunopathological ...manifestations (IMs), and progression to systemic lupus erythematosus (SLE). No risk factors for these outcomes are known. Specifically, whether age at ITP diagnosis, sex, or IMs impact cITP outcomes is unknown. We report the outcomes of patients with pediatric cITP from the French nationwide prospective cohort OBS'CEREVANCE. We used multivariate analyses to investigate the effect of age at ITP diagnosis, sex, and IMs on cITP outcomes. We included 886 patients with a median (min‐max) follow‐up duration of 5.3 (1.0–29.3) years. We identified an age cutoff that dichotomized the risk of the outcomes and defined two risk groups: patients with ITP diagnosed <10 years (children) and ≥ 10 years (adolescents). Adolescents had a two to four‐fold higher risk of grade ≥3 bleeding, second‐line treatment use, clinical and biological IMs, and SLE diagnosis. Moreover, female sex and biological IMs were independently associated with higher risks of biological IMs and SLE diagnosis, second‐line treatment use, and SLE diagnosis, respectively. The combination of these three risk factors defined outcome‐specific risk groups. Finally, we showed that patients clustered in mild and severe phenotypes, more frequent in children and adolescents, respectively. In conclusion, we identified that age at ITP diagnosis, sex, and biological IMs impacted the long‐term outcomes of pediatric cITP. We defined risk groups for each outcome, which will help clinical management and further studies.
Our aim was to identify national consensus criteria for the management of children with chemotherapy-induced febrile neutropenia (FN), for evidence-based step-down treatment approaches for patients ...classified at low risk of severe infection. In 2018, a five-section, 38-item survey was e-mailed to all pediatric hematology and oncology units in France (
= 30). The five sections contained statements on possible consensus criteria for the (i) definition of FN, (ii) initial management of children with FN, (iii) conditions required for initiating step-down therapy in low-risk patients, (iv) management strategy for low-risk patients, and (v) antibiotic treatment on discharge. Consensus was defined by respondents' combined answers (somewhat agree and strongly agree) at 75% or more. Sixty-five physicians (participation rate: 58%), all specialists in pediatric onco-hematology, from 18 centers completed the questionnaire. A consensus was reached on 22 of the 38 statements, including the definition of FN, the criteria for step-down therapy in low-risk children, and the initial care of these patients. There was no consensus on the type and duration of antibiotic therapy on discharge. In conclusion, a consensus has been reached on the criteria for initiating evidence-based step-down treatment of children with FN and a low risk of severe infection but not for the step-down antimicrobial regimen.
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