Publications by authors named "Thierry LeBlanc"

Fanconi Anemia (FA) is an inherited disorder associated with profound DNA repair defects, marked by failure to thrive, congenital malformations, progressive bone marrow failure (BMF), and an increased susceptibility to cancer. Clinical manifestations of FA vary widely, with BMF and clonal evolution predominantly affecting younger individuals, while adults are more frequently presenting with solid tumors. Individuals with FA are at a 500-fold increased risk of developing head and neck squamous cell carcinoma (HNSCC), which tends to appear at a median age of 30 years, often at advanced stages with only a 57% two-year survival rate.

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Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GROUPOS and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists.

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Hodgkin lymphoma (HL) is one of the most common cancers in adolescents and young adults (AYA). Paediatric and adult therapeutic strategies diverge while sharing the common objective: maintaining optimal efficacy with less long-term toxicity. However, few studies have compared the outcome of AYA treated according to one or the other approaches.

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Importance: Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).

Objective: To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.

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Importance: The current standard-of-care salvage therapy in relapsed/refractory classic Hodgkin lymphoma (cHL) includes consolidation high-dose chemotherapy (HDCT)/autologous stem cell transplant (aSCT).

Objective: To investigate whether presalvage risk factors and fludeoxyglucose-18 (FDG) positron emission tomography (PET) response to reinduction chemotherapy can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates.

Design, Setting, And Participants: EuroNet-PHL-R1 was a nonrandomized clinical trial that enrolled patients younger than 18 years with first relapsed/refractory cHL across 68 sites in 13 countries in Europe between January 2007 and January 2013.

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Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

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Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management.

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Adolescents and young adults (AYAs) with immune thrombocytopenia (ITP) exhibit distinct clinical features and needs, defying categorization as either adults or children. Previous findings revealed a 50% risk of chronic disease at 12 months, yet the long-term course remains unclear. This study aimed to delineate the clinical and laboratory characteristics of AYAs with chronic primary ITP.

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Article Synopsis
  • * A study from a tertiary care center between 2010 and 2022 revealed a significant increase in cases (3.3-fold) during the SARS-CoV-2 pandemic compared to pre-pandemic years, though liver characteristics remained similar across both periods.
  • * Early initiation of immunosuppressive therapy was noted during the pandemic, and conducting liver biopsies is recommended for undetermined acute hepatitis cases, even if autoimmune antibodies are negative.
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  • The study examines the blood-related characteristics and overall prognosis of 127 patients with telomere biology disorders (TBD) who were diagnosed after age 15, highlighting a lack of data on this topic.
  • At diagnosis, significant haematological issues were present in nearly 76% of patients, with bone marrow failure (BMF) being the most common, affecting 46.5% of the cases, while some patients also developed additional complications over time.
  • The findings suggest that BMF patients tend to be younger and have a better survival rate compared to those with higher-risk blood cancers, indicating TBD as a complex multi-organ disease needing further research on its evolutionary nature and outcomes.
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  • * In 2023, the Pediatric ITP Consortium defined refractory pediatric ITP as no platelet response after treatment with all eligible emergent therapies.
  • * Patients with high disease burden or lack of platelet response, despite various treatments, are identified as a challenging group that requires further research and the potential for new treatment options.
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  • Hypodense volumes (HDV) in mediastinal masses were identified in 29.7% of Hodgkin lymphoma patients analyzed from a study involving 1178 staging CT scans.
  • These HDVs were predominantly found in larger tumor volumes and exhibited various patterns, including single lesions in 69.4% of cases and well delineated lesions in 70.1% of cases.
  • Patients with HDV displayed more severe symptoms and had a lower 5-year progression-free survival rate (79.6% for HDV > 40 ml) compared to those with lower HDV levels, indicating a potential connection between HDV presence and poorer prognosis in Hodgkin lymphoma.
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  • This study introduces a promising approach for gene therapy in Diamond Blackfan anemia (DBA), focusing on patients with mutations in the RPS19 gene and demonstrating a safe and effective treatment method.
  • Unlike Fanconi anemia, DBA patients have a healthy reserve of hematopoietic stem cells, making them suitable candidates for this therapy without significant complications.
  • Two novel lentiviral vectors were developed to deliver RPS19, showing successful restoration of red blood cell development in lab experiments, along with confirming safety and potential long-term benefits in hematopoietic cell function.
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Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care.

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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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  • - 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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  • - Diamond-Blackfan anemia (DBA) is the first ribosomopathy identified in humans, characterized by a specific type of anemia caused by issues in red blood cell development and ribosomal protein deficiencies affecting 24 different genes.
  • - Around 50% of DBA cases also present with various physical malformations, and the condition is linked to malfunctioning ribosomal RNA maturation, which contributes to ineffective blood cell production.
  • - The complexity of DBA symptoms arises from multiple mechanisms, including defects in gene translation, chaperone deficits, free heme toxicity, and p53 activation, leading to a wide range of clinical presentations even among family members.
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  • New lung lesions were identified in 9.2% of pediatric Hodgkin lymphoma patients after two chemotherapy cycles, indicating that these may not be related to cancer progression.
  • The study utilized interim CT scans to differentiate between true lung metastases and benign lung lesions, using guidelines from the Fleischner glossary for classification.
  • Most newly detected pulmonary nodules were small (under 10 mm) and often regressed by the time of later evaluations, suggesting they were likely not harmful manifestations associated with the original lymphoma.
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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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Background And Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases.

Approach And Results: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations.

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Juvenile myelomonocytic leukemia (JMML) and myelodysplastic syndromes (MDS) of children are rare and aggressive diseases. They both have the particularity of being very frequently associated with an underlying predisposition syndrome, which must be systematically investigated by meticulous clinical exam completed by molecular analysis on fibroblasts, in order to guarantee the best therapeutic management. New generation sequencing techniques have made it possible to better define the landscape of constitutional predisposing pathologies, to understand the clonal evolution that leads to the development of hematological malignancies and to identify new prognostic markers.

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Background: Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification.

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Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES).

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Nodular Lymphocyte predominant Hodgkin lymphoma (NLPHL) are rare lymphomas in pediatric patients comprising less than 10 % of all Hodgkin lymphoma (HL). They are for the most part diagnosed at stage I or II and indolent with lymphadenopathy often preceding the diagnosis by many months/years. Survival is excellent.

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