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Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.
Herman, S E M; Niemann, C U; Farooqui, M; Jones, J; Mustafa, R Z; Lipsky, A; Saba, N; Martyr, S; Soto, S; Valdez, J; Gyamfi, J A; Maric, I; Calvo, K R; Pedersen, L B; Geisler, C H; Liu, D; Marti, G E; Aue, G; Wiestner, A.
Afiliação
  • Herman SE; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Niemann CU; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Farooqui M; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Jones J; 1] Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA [2] Medical Research Scholars Program, National Institutes of Health, Bethesda, MD, USA.
  • Mustafa RZ; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Lipsky A; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Saba N; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Martyr S; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Soto S; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Valdez J; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Gyamfi JA; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Maric I; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Calvo KR; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
  • Pedersen LB; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Geisler CH; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Liu D; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Marti GE; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Aue G; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Wiestner A; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Leukemia ; 28(11): 2188-96, 2014 Nov.
Article em En | MEDLINE | ID: mdl-24699307
ABSTRACT
Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average increase in ALC was 66%, and in>40% of patients the ALC peaked within 24 h of initiating treatment. Circulating CLL cells on day 2 showed increased Ki67 and CD38 expression, indicating an efflux of tumor cells from the tissue compartments into the blood. The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly, in patients with a high baseline ALC the relative increase was mild and resolution rapid. After two cycles of treatment the disease burden in the LN, bone marrow and spleen decreased irrespective of the relative change in ALC. Whole-blood viscosity was dependent on both ALC and hemoglobin. No adverse events were attributed to the lymphocytosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Pirimidinas / Receptores de Antígenos de Linfócitos B / Leucemia Linfocítica Crônica de Células B / Transdução de Sinais / Linfocitose Tipo de estudo: Prognostic_studies Limite: Aged / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Pirimidinas / Receptores de Antígenos de Linfócitos B / Leucemia Linfocítica Crônica de Células B / Transdução de Sinais / Linfocitose Tipo de estudo: Prognostic_studies Limite: Aged / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article