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  1. Article ; Online: From vacuoles to VEXAS.

    Heiblig, Maël / Sujobert, Pierre

    Rheumatology (Oxford, England)

    2023  Volume 62, Issue 12, Page(s) 3780–3781

    MeSH term(s) Humans ; Vacuoles ; Mutation
    Language English
    Publishing date 2023-07-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/kead392
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  2. Article ; Online: VEXAS syndrome, a new kid on the block of auto-inflammatory diseases: A hematologist's point of view.

    Heiblig, Maël / Patel, Bhavisha / Jamilloux, Yvan

    Best practice & research. Clinical rheumatology

    2023  Volume 37, Issue 1, Page(s) 101861

    Abstract: The recently discovered VEXAS syndrome is caused by the clonal expansion of hematopoietic stem or progenitor cells with acquired mutations in UBA1 gene, which encodes for a key enzyme of the ubiquitylation proteasome system. As a result, a shorter ... ...

    Abstract The recently discovered VEXAS syndrome is caused by the clonal expansion of hematopoietic stem or progenitor cells with acquired mutations in UBA1 gene, which encodes for a key enzyme of the ubiquitylation proteasome system. As a result, a shorter cytoplasmic isoform of UBA1 is transcribed, which is non-functional. The disease is characterized by non-specific and highly heterogeneous inflammatory manifestations and macrocytic anemia. VEXAS syndrome is a unique acquired hematological monogenic disease with unexpected association with hematological neoplasms. Despite its hematopoetic origin, patients with VEXAS syndrome usually present with multi-systemicinflammatory disease and are treated by physicians from many different specialties (rheumatologists, dermatologists, hematologistis, etc.). Furthermore, manifestations of VEXAS may fulfill criteria for existing diseases: relapsing polychondritis, giant cell arteritis, polyarteritis nodosa, and myelodysplastic syndrome. The goal of this review is to depict VEXAS syndrome from a hematologic point of view regarding its consequences on hematopoiesis and the current strategies on therapeutic interventions.
    MeSH term(s) Humans ; Giant Cell Arteritis ; Mutation/genetics ; Myelodysplastic Syndromes ; Proteasome Endopeptidase Complex
    Chemical Substances Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2023-08-30
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2052323-3
    ISSN 1532-1770 ; 1521-6942
    ISSN (online) 1532-1770
    ISSN 1521-6942
    DOI 10.1016/j.berh.2023.101861
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  3. Article ; Online: VEXAS: is it time to reshape the nosology of clonal hematopoiesis?

    Sujobert, Pierre / Largeaud, Laetitia / Jamilloux, Yvan / Heiblig, Maël / Kosmider, Olivier

    Expert review of hematology

    2023  Volume 16, Issue 7, Page(s) 495–499

    Abstract: Introduction: The recent description of VEXAS (for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) challenges the nosological framework of myelodysplastic syndromes.: Areas covered: Clonal expansion driven by somatic mutations in cancer ... ...

    Abstract Introduction: The recent description of VEXAS (for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) challenges the nosological framework of myelodysplastic syndromes.
    Areas covered: Clonal expansion driven by somatic mutations in cancer genes has been largely described in healthy aging individuals. Regarding hematopoiesis, the prevalence of clonal hematopoiesis has blurred the line between normal and pathological, especially for the definition of myelodysplastic syndromes. VEXAS syndrome further challenges the nosology as this clonal disease of hematopoiesis is also associated with dysplastic features and cytopenias.
    Expert opinion: In this perspective, we discuss whether VEXAS should be considered a genuine myelodysplastic syndrome and propose a conceptual framework to refine the nosology, based on the distinction of clonal hematopoiesis of indeterminate potential (CHIP), clonal hematopoiesis of hematological significance, and clonal hematopoiesis of other significance.
    MeSH term(s) Humans ; Clonal Hematopoiesis/genetics ; Mutation ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Hematopoiesis/genetics
    Language English
    Publishing date 2023-05-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2516804-6
    ISSN 1747-4094 ; 1747-4086
    ISSN (online) 1747-4094
    ISSN 1747-4086
    DOI 10.1080/17474086.2023.2209715
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  4. Article ; Online: Impact of Age on Poly(ADP-Ribose) Polymerase Inhibitor (PARPi)-Induced Lymphopenia: A Scoping Review of the Literature and Internal Analysis of a Retrospective Database.

    Antherieu, Gabriel / Heiblig, Maël / Freyer, Gilles / Ghesquieres, Hervé / Falandry, Claire

    Drugs & aging

    2023  Volume 40, Issue 5, Page(s) 397–405

    Abstract: Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) are increasingly used in oncology; their hematological toxicities affect classically red, platelet and neutrophil lineages, but some opportunistic infections have been reported concomitantly to ... ...

    Abstract Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) are increasingly used in oncology; their hematological toxicities affect classically red, platelet and neutrophil lineages, but some opportunistic infections have been reported concomitantly to deep lymphopenias.
    Objective: This study was designed to provide an external and internal analysis of the crossed impacts of PARPi and age on lymphopenia risk.
    Patients and methods: A scoping review was performed on the PubMed and Embase databases to assess the reporting of lymphocyte rates in original studies on PARPi treatment for adult patients up to 1 April 2022. A retrospective cohort was extracted from the medical charts of all patients treated for gynecological cancer at our institution from 2015 to 2022 in accordance with ethical regulations.
    Results: The scoping review research strategy retrieved 5840 abstracts; 225 studies were selected for full-text analysis. Lymphopenia was reported in 41.8% of the studies; frequency of all-grade and grade ≥ 3 lymphopenia reached 20.5% and 8.9%, respectively. Grade ≥ 3 lymphopenia was significantly higher in studies including older patients (median age ≥ 60 years vs. < 60 years), at 7.5% vs. 10.3% (p < 0.0001). PARIB-OLD-HCL included 46 patients, 19 of whom were aged < 70 years (median 44 years) and 27 of whom were aged ≥ 70 years (median 79 years); the frequency of all-grade and grade ≥ 3 lymphopenia reached 67% (< 70 years: 63%; ≥ 70 years: 70%) and 13% (< 70 years: 5%; ≥ 70 years: 19%), respectively.
    Conclusion: Lymphopenia events were much more frequent in real-life than in previously reported studies, particularly in older patients. Future work is needed to improve patient follow-up and discuss prophylactic strategies.
    MeSH term(s) Humans ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Retrospective Studies ; Antineoplastic Agents/therapeutic use ; Neoplasms/drug therapy ; Lymphopenia/chemically induced
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors ; Antineoplastic Agents
    Language English
    Publishing date 2023-04-20
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 1075770-3
    ISSN 1179-1969 ; 1170-229X
    ISSN (online) 1179-1969
    ISSN 1170-229X
    DOI 10.1007/s40266-023-01023-7
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  5. Article ; Online: VEXAS: where do we stand 2 years later?

    Sujobert, Pierre / Heiblig, Maël / Jamilloux, Yvan

    Current opinion in hematology

    2022  Volume 30, Issue 2, Page(s) 64–69

    Abstract: Purpose of review: Two years after the recognition of VEXAS (for Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, we propose an extensive review of the current understanding of VEXAS pathophysiology and therapeutic options.: Recent ... ...

    Abstract Purpose of review: Two years after the recognition of VEXAS (for Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, we propose an extensive review of the current understanding of VEXAS pathophysiology and therapeutic options.
    Recent findings: Among the nearly 150 articles published about VEXAS, some have provided determinant insights into VEXAS pathophysiology and treatment. Clinical data from retrospective series support the JAK inhibitor ruxolitinib as the most efficient strategy to control inflammation, and interesting results were also described with azacytidine. Allogeneic stem cell transplantation remains the only curative option, but should be proposed to carefully selected patients.
    Summary: Although waiting for more robust evidence from prospective clinical trials, therapeutic options emerge from retrospective studies. We propose a set of criteria that should be systematically reported to harmonize the evaluation of therapeutic outcomes. This will allow the collection of high-quality data and facilitate their subsequent meta-analysis with the overall aim of improving the management of VEXAS patients.
    MeSH term(s) Humans ; Azacitidine ; Hematopoietic Stem Cell Transplantation ; Mutation ; Prospective Studies ; Retrospective Studies
    Chemical Substances Azacitidine (M801H13NRU)
    Language English
    Publishing date 2022-12-30
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1153887-9
    ISSN 1531-7048 ; 1065-6251
    ISSN (online) 1531-7048
    ISSN 1065-6251
    DOI 10.1097/MOH.0000000000000750
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  6. Article ; Online: Antibody-based therapy for acute myeloid leukemia: a review of phase 2 and 3 trials.

    Thomas, Xavier / Elhamri, Mohamed / Deloire, Alexandre / Heiblig, Maël

    Expert opinion on emerging drugs

    2022  Volume 27, Issue 2, Page(s) 169–185

    Abstract: Introduction: Despite recent advances in the treatment of adult acute myeloid leukemia (AML), the clinical outcome of patients continues to be unsatisfactory especially among older patients, those with a high-risk profile, and in the relapsed/refractory ...

    Abstract Introduction: Despite recent advances in the treatment of adult acute myeloid leukemia (AML), the clinical outcome of patients continues to be unsatisfactory especially among older patients, those with a high-risk profile, and in the relapsed/refractory setting. For this reason, recent clinical trials have explored novel therapeutic agents either used alone or in combination with intensive chemotherapy or low-intensity treatments.
    Areas covered: The current paper reviews the clinical development of monoclonal antibody-based therapies in AML, their current status and phases 2 and 3 prospective trials.
    Expert opinion: Monoclonal antibody-based therapies demonstrated efficacy and tolerability in several clinical trials, especially when used in combination either with '3 + 7' chemotherapy or with low-intensity treatments. Additional studies are needed to determine new antigens for antibody-based therapies that target leukemia stem cells and spare normal hematopoiesis. Phase 2 and 3 additional clinical trial data are needed to assess the promise of first trials, especially regarding chimeric antigen receptor T cells redirected against myeloid antigens and immune checkpoint inhibitor therapies.
    MeSH term(s) Adult ; Antibodies, Monoclonal/adverse effects ; Clinical Trials, Phase II as Topic ; Humans ; Immunotherapy ; Leukemia, Myeloid, Acute/drug therapy ; Prospective Studies
    Chemical Substances Antibodies, Monoclonal
    Language English
    Publishing date 2022-07-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2061369-6
    ISSN 1744-7623 ; 1472-8214
    ISSN (online) 1744-7623
    ISSN 1472-8214
    DOI 10.1080/14728214.2022.2094365
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  7. Article: Acute Promyelocytic Leukemia.

    Thomas, Xavier / Heiblig, Maël

    Cancers

    2020  Volume 12, Issue 12

    Abstract: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) cytogenetically characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion between the promyelocytic leukemia ( ...

    Abstract Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) cytogenetically characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the fusion between the promyelocytic leukemia (
    Language English
    Publishing date 2020-12-11
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12123718
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  8. Article ; Online: An evaluation of glasdegib for the treatment of acute myelogenous leukemia.

    Thomas, Xavier / Heiblig, Maël

    Expert opinion on pharmacotherapy

    2020  Volume 21, Issue 5, Page(s) 523–530

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzimidazoles/administration & dosage ; Benzimidazoles/adverse effects ; Benzimidazoles/therapeutic use ; Cytarabine/administration & dosage ; Cytarabine/adverse effects ; Cytarabine/therapeutic use ; Hedgehog Proteins/antagonists & inhibitors ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/metabolism ; Phenylurea Compounds/administration & dosage ; Phenylurea Compounds/adverse effects ; Phenylurea Compounds/therapeutic use ; Signal Transduction ; United States ; United States Food and Drug Administration
    Chemical Substances Benzimidazoles ; Hedgehog Proteins ; Phenylurea Compounds ; Cytarabine (04079A1RDZ) ; glasdegib (K673DMO5H9)
    Language English
    Publishing date 2020-02-06
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2001535-5
    ISSN 1744-7666 ; 1465-6566
    ISSN (online) 1744-7666
    ISSN 1465-6566
    DOI 10.1080/14656566.2020.1713094
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  9. Article ; Online: Chronic myelomonocytic leukemia transdifferentiation landscape: From histiocytosis to blastic plasmacytoid dendritic cell neoplasm.

    Antherieu, Gabriel / Donzel, Marie / Balme, Brigitte / Traverse-Glehen, Alexandra / Heiblig, Maël

    American journal of hematology

    2023  Volume 98, Issue 8, Page(s) 1343–1345

    MeSH term(s) Humans ; Leukemia, Myelomonocytic, Chronic ; Cell Transdifferentiation ; Myeloproliferative Disorders ; Acute Disease ; Dendritic Cells ; Histiocytosis ; Skin Neoplasms
    Language English
    Publishing date 2023-02-28
    Publishing country United States
    Document type Case Reports
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
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    ISSN 0361-8609
    DOI 10.1002/ajh.26876
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  10. Article ; Online: Emerging pharmacotherapies for elderly acute myeloid leukemia patients.

    Thomas, Xavier / Elhamri, Mohamed / Heiblig, Maël

    Expert review of hematology

    2020  Volume 13, Issue 6, Page(s) 619–643

    Abstract: Introduction: Acute myeloid leukemia (AML) is a disease mainly seen in the elderly, for which treatment is undergoing rapid changes. Although recent studies have supported the survival benefit of induction chemotherapy in fit patients and that of ... ...

    Abstract Introduction: Acute myeloid leukemia (AML) is a disease mainly seen in the elderly, for which treatment is undergoing rapid changes. Although recent studies have supported the survival benefit of induction chemotherapy in fit patients and that of hypomethylating agents (HMAs) in non-induction candidates, treatment of this patient age population remains a significant challenge for the treating oncologist.
    Areas covered: In this review, we will examine effectiveness and safety outcomes of upcoming novel treatment strategies in elderly (≥60 years old) patients with AML, highlight the current literature and ongoing trials able to maximize therapeutic options in this heterogeneous patient population.
    Expert opinion: Current developments including new chemotherapeutic strategies and combinations of HMAs with novel drugs targeting epigenetic or immunomodulatory pathways are underway to improve patient survival and quality of life.
    MeSH term(s) Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2020-05-13
    Publishing country England
    Document type Journal Article ; Review ; Video-Audio Media
    ZDB-ID 2516804-6
    ISSN 1747-4094 ; 1747-4086
    ISSN (online) 1747-4094
    ISSN 1747-4086
    DOI 10.1080/17474086.2020.1758058
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