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.
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.
Department of Hematology, Yokohama City University Medical Center, Kanagawa, Japan.
Maki
M
Hagihara
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Noriyoshi
N
Iriyama
Department of Hematology, National Hospital Organization Mito Medical Center, Ibaraki, Japan.
Chikashi
C
Yoshida
Division of Hematology and Oncology, Japanese Red Cross Society, Narita Red Cross Hospital, Chiba, Japan.
Hisashi
H
Wakita
Department of Hematology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Shigeru
S
Chiba
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Shinichiro
S
Okamoto
Department of Hematology and Clinical Oncology, Kagawa Prefectural Central Hospital, Kagawa, Japan.
Kimihiro
K
Kawakami
Department of Hematology, National Hospital Organization Disaster Medical Center, Tokyo, Japan.
Naoki
N
Takezako
Department of Hematology, Ohme Municipal General Hospital, Tokyo, Japan.
Takashi
T
Kumagai
Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Koiti
K
Inokuchi
Department of Hematology, Tokyo Medical University, Tokyo, Japan.
Kazuma
K
Ohyashiki
Department of Hematology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan.
Jun
J
Taguchi
Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Shingo
S
Yano
Division of Hematology and Oncology, Gunma Prefectural Cancer Center, Gunma, Japan.
Tadahiko
T
Igarashi
Department of Hematology, Tokyo Metropolitan Tama Synthesis Medical Center, Tokyo, Japan.
Yasuji
Y
Kouzai
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Satoshi
S
Morita
Tokai Central Hospital, Gifu, Japan.
Junichi
J
Sakamoto
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Hisashi
H
Sakamaki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069439:Dasatinib / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors
C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib