Publications by authors named "Guy Leverger"

An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells.

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Refractory chronic immune thrombocytopenia (r-cITP) is one of the most challenging situations in chronic immune thrombocytopenia (cITP). Pediatric r-cITP is inconsistently defined in literature, contributing to the scarcity of data. Moreover, no evidence is available to guide the choice of treatment.

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  • * Three new recurring KMT2A-rearranged groups were identified, and a significant variation in 5-year event-free survival rates was observed across 13 different groups, highlighting the impact of genetic factors on patient outcomes.
  • * The research suggests incorporating five specific adverse-risk KMT2A fusions into current risk stratification models and calls for further studies to confirm the associations
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  • - Kabuki syndrome (KS) is now categorized as a rare disease linked to genetic variants in KMT2D and KDM6A, primarily characterized by intellectual disability and unique facial features, often seen in patients with autoimmune cytopenia (AIC).
  • - A study involving 11 patients with KS and AIC revealed that all had chronic immune thrombocytopenic purpura, with many also experiencing Evans syndrome and low immunoglobulin levels, highlighting a median of 8 KS-related symptoms per patient.
  • - Despite ongoing treatment needs, with eight patients receiving second-line therapies like rituximab, the research advocates for prompt identification of KS by pediatricians to ensure effective clinical management and long-term care strategies.
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Autoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS'CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described.

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The prognostic impact of PICALM::MLLT10 status in childhood leukaemia is not well described. Ten International Berlin Frankfurt Münster-affiliated study groups and the Children's Oncology Group collaborated in this multicentre retrospective study. The presence of the PICALM::MLLT10 fusion gene was confirmed by fluorescence in situ hybridization and/or RNA sequencing at participating sites.

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Background: A growing number of centers worldwide are preserving testicular tissue (TT) of young boys at risk of fertility loss to preserve their fertility. Data in this regard are scarce and experience sharing is essential to the optimization of the process.

Objectives: This report of our 10-year activity of pediatric fertility preservation (FP) has the objective to (1) improve knowledge regarding the feasibility, acceptability, safety, and potential usefulness of the procedure; (2) analyze the impact of chemotherapy on spermatogonia in the cryopreserved TT.

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Loss of NBEAL2 function leads to grey platelet syndrome (GPS), a bleeding disorder characterized by macro-thrombocytopenia and α-granule-deficient platelets. A proportion of patients with GPS develop autoimmunity through an unknown mechanism, which might be related to the proteins NBEAL2 interacts with, specifically in immune cells. Here we show a comprehensive interactome of NBEAL2 in primary T cells, based on mass spectrometry identification of altogether 74 protein association partners.

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Current immune thrombocytopenia (ITP) guidelines target children and adults, leading to oversimplification. Adolescents and young adults (AYAS) comprise a separate group with distinct health and psychosocial issues. This study aimed to describe the clinical presentation and therapeutic strategies of ITP among AYAS.

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  • A study by the I-BFM-SG on childhood rearranged acute myeloid leukemia (AML) revealed that the type of fusion partner plays a significant role in prognosis, and it also explored the effectiveness of flow cytometry-based measurable residual disease (flow-MRD) and allogeneic stem-cell transplantation (allo-SCT) in improving outcomes during first complete remission.
  • The research involved 1,130 children diagnosed with rearranged AML, who were categorized into high-risk and non-high-risk groups based on their fusion partners, and it focused on the relationship between flow-MRD levels and long-term survival rates.
  • Results showed that the high-risk group had significantly worse event-free survival, cumulative incidence of relapse, and overall survival
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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.

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Familial platelet disorder with associated myeloid malignancy (FPD-MM; OMIM 601399) is related to germline mutation. The pathogenicity of variants was initially linked to FPD-MM phenotype, but the discovery of new variants through the expansion of genetic explorations in leukaemia is questioning this assertion. In this study, we add 10 families with germline variant explored at Armand Trousseau Hospital for leukaemia diagnosis or thrombocytopenia, to the 259 described so far.

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  • Patients with Fanconi anemia (FA) show chromosome instability, leading to exhaustion of hematopoietic stem cells and a higher risk of developing poor-prognosis myeloid leukemia.
  • A study involving 62 patients revealed unique mutations and structural variants that resemble BRCA-related cancers, with many patients showing chromosome 1q gain linked to MDM4 trisomy, which downregulates p53 signaling.
  • MDM4 triplication not only enhances the survival of FA stem cells but also promotes leukemia development, suggesting that targeting MDM4 could be a potential therapeutic strategy to disrupt this pathway.
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  • Pyruvate Kinase (PK) deficiency is a common enzyme defect that leads to congenital hemolytic anemia, often evident from birth.
  • A family with a history of PK deficiency underwent prenatal management for their third child after previous complications from the condition; ultrasound monitoring helped identify severe fetal anemia, resulting in two intrauterine red blood cell transfusions.
  • Successful treatment allowed the third child to be born healthy, emphasizing the importance of fetal monitoring and management in families with a diagnosed proband for PK deficiency.
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  • Hypodiploidy, characterized by a low modal number of chromosomes (45 or lower), is a known high-risk factor in pediatric acute lymphoblastic leukemia but hasn't been studied in pediatric acute myeloid leukemia (AML) until now.
  • This study analyzed data from 81 children under 18 with hypodiploid karyotypes diagnosed with AML, finding that more severe hypodiploidy (modal numbers ≤ 44) led to significantly worse event-free survival (EFS) and overall survival (OS) rates compared to those with a modal number of 45.
  • The results highlight that pediatric hypodiploid AML is a rare but challenging subgroup with poor prognosis, as even treatments like allogeneic
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Splenectomy is effective in ∼70% to 80% of pediatric chronic immune thrombocytopenia (cITP) cases, and few data exist about it in autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES). Because of the irreversibility of the procedure and the lack of predictions regarding long-term outcomes, the decision to undertake splenectomy is difficult in children. We report here factors associated with splenectomy outcomes from the OBS'CEREVANCE cohort, which prospectively includes French children with autoimmune cytopenia (AIC) since 2004.

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Despite major therapeutic improvements, children with relapsed/refractory Acute Myeloid Leukaemia still have poor outcomes and overall survival does not exceed 40%. New treatments are required to improve their outcome; Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate antibody, is a potent cytotoxic agent whose efficacy has been demonstrated mainly in adults. The main objective of this retrospective multicentre study was to assess the outcome of children treated, between February 2008 and August 2019, with GO at a single 4.

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Background: Invasive fungal infections (IFI) are an important cause of morbidity and mortality in children with leukaemia. International guidelines recommend a monotherapy for most IFI. The use of antifungal combination therapy (ACT) has been reported, but clinical data supporting these combinations are scarce, particularly in paediatrics.

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Peripheral neuroblastic tumors are the most common extracranial solid tumors in children. On the other hand, diarrheal neuroblastic tumors are quite rare and not easy to diagnose in the early stage. We report a case of neuroblastic tumor in a 2-year old girl presenting with aqueous diarrhea caused by paraneoplasic secretion of VIP.

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Background And Aims: Extracranial malignant rhabdoid tumours are tumours that mainly affect young children and have a poor prognosis. In 2014, the European Paediatric Soft-tissue sarcoma Study Group developed treatment recommendations consisting in intensive dose chemotherapy every 2 weeks using vincristine-doxorubicin-cyclophosphamide (VDCy) and ifosfamide-etoposide (IE) associated with early surgery and irradiation of tumour sites.

Methods: A retrospective study was conducted on children treated in France by these new recommendations up to January 2019.

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