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Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy.
Friedman, Joshua S; Durham, Benjamin H; Reiner, Anne S; Yabe, Mariko; Petrova-Drus, Kseniya; Dogan, Ahmet; Pulitzer, Melissa; Busam, Klaus J; Francis, Jasmine H; Rampal, Raajit K; Ulaner, Gary A; Reddy, Ryan; Yeh, Randy; Hatzoglou, Vaios; Lacouture, Mario E; Rotemberg, Veronica; Mazor, Roei D; Hershkovitz-Rokah, Oshrat; Shpilberg, Ofer; Goyal, Gaurav; Go, Ronald S; Abeykoon, Jithma P; Rech, Karen; Morlote, Diana; Fidai, Shiraz; Gannamani, Vedavyas; Zia, Maryam; Abdel-Wahab, Omar; Panageas, Katherine S; Rosenblum, Marc K; Diamond, Eli L.
Afiliação
  • Friedman JS; Departments of Neurology, Neurosurgery, and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Durham BH; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Reiner AS; Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA.
  • Yabe M; Department of Molecular Pharmacology, Sloan Kettering Institute, New York, New York, USA.
  • Petrova-Drus K; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Dogan A; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Pulitzer M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Busam KJ; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Francis JH; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Rampal RK; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Ulaner GA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Reddy R; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Yeh R; Molecular Imaging and Therapy, Hoag Family Cancer Institute, Newport Beach, California, USA.
  • Hatzoglou V; Molecular Imaging and Therapy, University of Southern California, Los Angeles, California, USA.
  • Lacouture ME; Molecular Imaging and Therapy, Hoag Family Cancer Institute, Newport Beach, California, USA.
  • Rotemberg V; Molecular Imaging and Therapy, University of Southern California, Los Angeles, California, USA.
  • Mazor RD; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Hershkovitz-Rokah O; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Shpilberg O; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Goyal G; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Go RS; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Abeykoon JP; Clinic of Histiocytic Neoplasms, Institute of Hematology, Assuta Medical Center, Tel-Aviv, Israel.
  • Rech K; Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, Israel.
  • Morlote D; Translational Research Lab, Assuta Medical Centers, Tel-Aviv, Israel.
  • Fidai S; Clinic of Histiocytic Neoplasms, Institute of Hematology, Assuta Medical Center, Tel-Aviv, Israel.
  • Gannamani V; Adelson School of Medicine, Ariel University, Ariel, Israel.
  • Zia M; Department of Hematology Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Abdel-Wahab O; Rare Histiocytic Disorders Steering Committee of the Histiocyte Society.
  • Panageas KS; Rare Histiocytic Disorders Steering Committee of the Histiocyte Society.
  • Rosenblum MK; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
  • Diamond EL; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Br J Haematol ; 205(1): 127-137, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38613141
ABSTRACT
Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR] 17.34, 95% CI 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR 0.08, 95% CI 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Erdheim-Chester / Mutação Limite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Haematol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Erdheim-Chester / Mutação Limite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Haematol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos