Association of pleural effusion with an early molecular response in patients with newly diagnosed chronic-phase chronic myeloid leukemia receiving dasatinib: Results of a D-First study

Hagihara,Maki; Iriyama,Noriyoshi; Yoshida,Chikashi; Wakita,Hisashi; Chiba,Shigeru; Okamoto,Shinichiro; Kawakami,Kimihiro; Takezako,Naoki; Kumagai,Takashi; Inokuchi,Koiti; Ohyashiki,Kazuma; Taguchi,Jun; Yano,Shingo; Igarashi,Tadahiko; Kouzai,Yasuji; Morita,Satoshi; Sakamoto,Junichi; Sakamaki,Hisashi

doi:10.3892/or.2016.5110

Association of pleural effusion with an early molecular response in patients with newly diagnosed chronic-phase chronic myeloid leukemia receiving dasatinib: Results of a D-First study

Authors:
- Maki Hagihara
- Noriyoshi Iriyama
- Chikashi Yoshida
- Hisashi Wakita
- Shigeru Chiba
- Shinichiro Okamoto
- Kimihiro Kawakami
- Naoki Takezako
- Takashi Kumagai
- Koiti Inokuchi
- Kazuma Ohyashiki
- Jun Taguchi
- Shingo Yano
- Tadahiko Igarashi
- Yasuji Kouzai
- Satoshi Morita
- Junichi Sakamoto
- Hisashi Sakamaki
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Affiliations: Department of Hematology, Yokohama City University Medical Center, Kanagawa, Japan, Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan, Department of Hematology, National Hospital Organization Mito Medical Center, Ibaraki, Japan, Division of Hematology and Oncology, Japanese Red Cross Society, Narita Red Cross Hospital, Chiba, Japan, Department of Hematology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan, Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, Department of Hematology and Clinical Oncology, Kagawa Prefectural Central Hospital, Kagawa, Japan, Department of Hematology, National Hospital Organization Disaster Medical Center, Tokyo, Japan, Department of Hematology, Ohme Municipal General Hospital, Tokyo, Japan, Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan, Department of Hematology, Tokyo Medical University, Tokyo, Japan, Department of Hematology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan, Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan, Division of Hematology and Oncology, Gunma Prefectural Cancer Center, Gunma, Japan, Department of Hematology, Tokyo Metropolitan Tama Synthesis Medical Center, Tokyo, Japan, Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan, Tokai Central Hospital, Gifu, Japan, Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
Published online on: September 20, 2016 https://doi.org/10.3892/or.2016.5110
Pages: 2976-2982

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Abstract

Despite the efficacy and safety of dasatinib treatment for chronic-phase chronic myeloid leukemia (CML-CP), adverse effects such as pleural effusion (PE) are still a serious concern. We determined the clinical significance of PE incidence using patient data derived from the D-First clinical study. In the present study, chest radiography and quantification of specific lymphocyte subsets were performed routinely after initiation of dasatinib treatment. Among 52 patients with newly diagnosed CML-CP, 17 (33%) developed PE within 18 months after initial dasatinib administration, but all cases were moderate (Grade 1, 10 patients; Grade 2, 7 patients). CD56+ lymphocyte counts at 1 month correlated significantly with the incidence of PE, whereas lymphocytosis did not. The major molecular response (MMR) rate at 3 months (although not at later times) was significantly higher in PE-positive patients than PE-negative patients (59% versus 24%, respectively; P=0.013). Deep molecular response rates did not differ significantly between the PE groups at any time point during the observation period. Our results suggest that an immune-mediated mechanism involving natural killer cells underlies the development of PE in patients receiving dasatinib for 18 months. This mechanism likely promotes transient tumor regression in patients newly diagnosed with CML-CP.

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