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Predictors of clonal evolution and myeloid neoplasia following immunosuppressive therapy in severe aplastic anemia.
Groarke, Emma M; Patel, Bhavisha A; Shalhoub, Ruba; Gutierrez-Rodrigues, Fernanda; Desai, Parth; Leuva, Harshraj; Zaimoku, Yoshitaka; Paton, Casey; Spitofsky, Nina; Lotter, Jennifer; Rios, Olga; Childs, Richard W; Young, David J; Dulau-Florea, Alina; Dunbar, Cynthia E; Calvo, Katherine R; Wu, Colin O; Young, Neal S.
Afiliação
  • Groarke EM; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Emma.Groarke@nih.gov.
  • Patel BA; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Shalhoub R; Office of Biostatistics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Gutierrez-Rodrigues F; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Desai P; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Leuva H; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Zaimoku Y; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Paton C; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Spitofsky N; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Lotter J; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Rios O; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Childs RW; Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Young DJ; Translational Stem Cell Biology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Dulau-Florea A; Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Dunbar CE; Translational Stem Cell Biology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Calvo KR; Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Wu CO; Office of Biostatistics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Young NS; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Leukemia ; 36(9): 2328-2337, 2022 09.
Article em En | MEDLINE | ID: mdl-35896822
ABSTRACT
Predictors, genetic characteristics, and long-term outcomes of patients with SAA who clonally evolved after immunosuppressive therapy (IST) were assessed. SAA patients were treated with IST from 1989-2020. Clonal evolution was categorized as "high-risk" (overt myeloid neoplasm [meeting WHO criteria for dysplasia, MPN or acute leukemia] or isolated chromosome-7 abnormality/complex karyotype without dysplasia or overt myeloid neoplasia) or "low-risk" (non-7 or non-complex chromosome abnormalities without morphological evidence of dysplasia or myeloid neoplasia). Univariate and multivariate analysis using Fine-Gray competing risk regression model determined predictors. Long-term outcomes included relapse, overall survival (OS) and hematopoietic stem cell transplant (HSCT). Somatic mutations in myeloid cancer genes were assessed in evolvers and in 407 patients 6 months after IST. Of 663 SAA patients, 95 developed clonal evolution. Pre-treatment age >48 years and ANC > 0.87 × 109/L were strong predictors of high-risk evolution. OS was 37% in high-risk clonal evolution by 5 years compared to 94% in low-risk. High-risk patients who underwent HSCT had improved OS. Eltrombopag did not increase high-risk evolution. Splicing factors and RUNX1 somatic variants were detected exclusively at high-risk evolution; DNMT3A, BCOR/L1 and ASXL1 were present in both. RUNX1, splicing factors and ASXL1 somatic mutations detected at 6 months after IST predicted high-risk evolution.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Anemia Aplástica / Transtornos Mieloproliferativos Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Anemia Aplástica / Transtornos Mieloproliferativos Idioma: En Ano de publicação: 2022 Tipo de documento: Article