Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase: Results of the D-first study

Noriyoshi Iriyama, Shin Fujisawa, 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

Research output: Contribution to journalArticle

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Abstract

Dasatinib is one of the key treatment options for chronic myeloid leukemia (CML) patients. Increase in lymphocyte counts has been known to be predictive of a good treatment response under dasatinib treatment as a second line therapy. However, clinical significance of lymphocyte dynamics in the upfront setting has yet to be clarified. To investigate the significance of lymphocyte dynamics in newly diagnosed chronic phase (CP)-CML, patient data of D-First study (ClinicalTrials.gov NCT01464411) were analyzed. Fifty-two CML-CP patients enrolled to this study were treated with dasatinib (100 mg day<sup>-1</sup>) and all were followed-up for 18 months. The incidence of lymphocyosis was observed in 14 (27%), but it was not associated with deep molecular response achievement. However, natural killer (NK) cell or cytotoxic T lymphocyte (CTL) counts at 1 month were significantly higher in patients with deep molecular response (DMR) by 18 months compared to those without DMR. When the patients were divided into two groups according to those calculated thresholds by receiver operating characteristic curve (407/μL for NK cells and 347/μL for CTLs), the cumulative DMR rates by 18 months were significantly better in higher value group compared to lower value group. In contrast, regulatory T cell counts were significantly lower at 12 and 15 months in patients achieved DMR. These results suggest the presence of dual effects of dasatinib on immune system through the cytotoxic lymphocytes activation and Treg deregulation in different periods in newly diagnosed CML-CP.

Original languageEnglish
Pages (from-to)819-824
Number of pages6
JournalAmerican Journal of Hematology
Volume90
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1

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Leukemia, Myeloid, Chronic Phase
Lymphocytes
Lymphocyte Count
Natural Killer Cells
Cytotoxic T-Lymphocytes
Regulatory T-Lymphocytes
Therapeutics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphocyte Activation
ROC Curve
Dasatinib
Immune System
Cell Count
Incidence

ASJC Scopus subject areas

  • Hematology

Cite this

Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase : Results of the D-first study. / Iriyama, Noriyoshi; Fujisawa, Shin; 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.

In: American Journal of Hematology, Vol. 90, No. 9, 01.09.2015, p. 819-824.

Research output: Contribution to journalArticle

Iriyama, N, Fujisawa, S, Yoshida, C, Wakita, H, Chiba, S, Okamoto, S, Kawakami, K, Takezako, N, Kumagai, T, Inokuchi, K, Ohyashiki, K, Taguchi, J, Yano, S, Igarashi, T, Kouzai, Y, Morita, S, Sakamoto, J & Sakamaki, H 2015, 'Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase: Results of the D-first study', American Journal of Hematology, vol. 90, no. 9, pp. 819-824. https://doi.org/10.1002/ajh.24096
Iriyama, Noriyoshi ; Fujisawa, Shin ; 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. / Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase : Results of the D-first study. In: American Journal of Hematology. 2015 ; Vol. 90, No. 9. pp. 819-824.
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AU - Yoshida, Chikashi

AU - Wakita, Hisashi

AU - Chiba, Shigeru

AU - Okamoto, Shinichiro

AU - Kawakami, Kimihiro

AU - Takezako, Naoki

AU - Kumagai, Takashi

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AU - Ohyashiki, Kazuma

AU - Taguchi, Jun

AU - Yano, Shingo

AU - Igarashi, Tadahiko

AU - Kouzai, Yasuji

AU - Morita, Satoshi

AU - Sakamoto, Junichi

AU - Sakamaki, Hisashi

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