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

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Abstract

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.

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Acknowledgments

This study was supported by the Epidemiological and Clinical Research Information Network (ECRIN). We thank Yumi Miyashita at ECRIN for collecting the data, and Yoshinori Yamamoto at BML for measuring the data.

Conflict of interest

K. N. received research funding from Novartis. S. O received research funding from Bristol-Myers Squibb. The remaining authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Department of Hematology, Ohme Municipal General Hospital, 4-16-5 Higashi-Ohme, Ohme, Tokyo, 198-0042, Japan

    Takashi Kumagai

  2. Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Eri Matsuki & Shinichiro Okamoto

  3. Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

    Koiti Inokuchi

  4. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Kazuteru Ohashi & Hisashi Sakamaki

  5. Department of Internal Medicine, Hitachi General Hospital, Hitachi, Ibaraki, Japan

    Atsushi Shinagawa

  6. Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan

    Jin Takeuchi

  7. Department of Hematology, National Hospital Organization Mito Medical Center, Ibaraki, Japan

    Chikashi Yoshida

  8. Division of Hematology and Oncology, Japanese Red Cross Society, Narita Red Cross Hospital, Narita, Japan

    Hisashi Wakita

  9. Department of Hematology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan

    Yasuji Kozai

  10. Division of Hematology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan

    Yukari Shirasugi

  11. Department of Hematology, Yokohama City University Medical Center, Yokohama, Japan

    Shin Fujisawa

  12. Division of Hematology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan

    Osamu Iwase

  13. Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

  14. Division of Oncology and Hematology, Department of Internal Medicine, Jikei University Kashiwa Hospital, Kashiwa, Japan

    Kaichi Nishiwaki

  15. Translational Research and Clinical Trial Center, Hokkaido University Hospital, Hokkaido, Japan

    Koji Oba

  16. Tokai Central Hospital, Kakamigahara, Japan

    Junichi Sakamoto

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  1. Takashi Kumagai
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Correspondence to Takashi Kumagai.

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Kumagai, T., Matsuki, E., Inokuchi, K. et al. Relative increase in lymphocytes from as early as 1 month predicts improved response to dasatinib in chronic-phase chronic myelogenous leukemia. Int J Hematol 99, 41–52 (2014). https://doi.org/10.1007/s12185-013-1483-9

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  • DOI: https://doi.org/10.1007/s12185-013-1483-9

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