Relative increase in lymphocytes from as early as 1 month predicts improved response to dasatinib in chronic-phase chronic myelogenous leukemia

被引:24
作者
Kumagai, Takashi [1 ]
Matsuki, Eri [2 ]
Inokuchi, Koiti [3 ]
Ohashi, Kazuteru [4 ]
Shinagawa, Atsushi [5 ]
Takeuchi, Jin [6 ]
Yoshida, Chikashi [7 ]
Okamoto, Shinichiro [2 ]
Wakita, Hisashi [8 ]
Kozai, Yasuji [9 ]
Shirasugi, Yukari [10 ]
Fujisawa, Shin [11 ]
Iwase, Osamu [12 ]
Yano, Shingo [13 ]
Nishiwaki, Kaichi [14 ]
Oba, Koji [15 ]
Sakamoto, Junichi [16 ]
Sakamaki, Hisashi [4 ]
机构
[1] Ohme Municipal Gen Hosp, Dept Hematol, Tokyo 1980042, Japan
[2] Keio Univ, Sch Med, Dept Internal Med, Div Hematol, Tokyo, Japan
[3] Nippon Med Sch, Dept Internal Med, Div Hematol, Tokyo 113, Japan
[4] Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Div Hematol, Tokyo, Japan
[5] Hitachi Gen Hosp, Dept Internal Med, Hitachi, Ibaraki, Japan
[6] Nihon Univ, Sch Med, Dept Hematol & Rheumatol, Tokyo, Japan
[7] Natl Hosp Org Mito Med Ctr, Dept Hematol, Ibaraki, Japan
[8] Narita Red Cross Hosp, Japanese Red Cross Soc, Div Hematol & Oncol, Narita, Japan
[9] Tokyo Metropolitan Tama Med Ctr, Dept Hematol, Tokyo, Japan
[10] Tokai Univ, Sch Med, Dept Internal Med, Div Hematol, Isehara, Kanagawa 25911, Japan
[11] Yokohama City Univ, Med Ctr, Dept Hematol, Yokohama, Kanagawa 232, Japan
[12] Tokyo Med Univ, Hachioji Med Ctr, Div Hematol, Tokyo 1608402, Japan
[13] Jikei Univ, Sch Med, Dept Internal Med, Div Clin Oncol & Hematol, Tokyo, Japan
[14] Jikei Univ, Kashiwa Hosp, Dept Internal Med, Div Hematol & Oncol, Tokyo, Japan
[15] Hokkaido Univ Hosp, Translat Res & Clin Trial Ctr, Sapporo, Hokkaido, Japan
[16] Tokai Cent Hosp, Kakamigahara, Japan
关键词
CML; Dasatinib; Lymphocytosis; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; NATURAL-KILLER; IN-VITRO; NK-CELLS; CYTOMEGALOVIRUS REACTIVATION; PHILADELPHIA-CHROMOSOME; IMATINIB; THERAPY; DISCONTINUATION;
D O I
10.1007/s12185-013-1483-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Lymphocytosis in response to dasatinib for chronic myelogenous leukemia (CML) may be associated with favorable response. However, it occurs at varying times and in a limited subset of patients. To identify early clinical markers for favorable responses applicable to all patients with or without lymphocytosis, we prospectively analyzed lymphocyte profiles of 50 Japanese CML patients treated with dasatinib after intolerance/resistance to imatinib. Although absolute lymphocyte counts did not differ significantly until 3 months between patients with complete molecular response (CMR) at 12 months and those without it, relative increases in lymphocyte compared with baselines differed significantly from 1 month. Patients with relative lymphocyte counts > 150 % at 1 month or > 200 % at 3 months had higher CMR rates at 12 months than others (57.9 vs. 23.3 %, P = 0.015, and 76.5 vs. 16.1 %, P < 0.0001, respectively). A relative increase in lymphocyte subset of CD57(+)CD14(-), CD8(+)T, or NK cells >200 % at 1 month was also significantly associated with a higher CMR rate. There were significant negative correlations between relative lymphocyte increases and BCR/ABL transcript levels. CD57(+)CD14(-) cells were a highly specific focus of proliferation. Relative increases in lymphocyte count and its subsets from 1 month are reliable early markers of favorable responses to dasatinib.
引用
收藏
页码:41 / 52
页数:12
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