title: Relative increase in lymphocytes from as early as 1 month predicts improved response to dasatinib in chronic-phase chronic myelogenous leukemia.
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.
authors.affiliation: Department of Hematology, Ohme Municipal General Hospital, 4-16-5 Higashi-Ohme, Ohme, Tokyo, 198-0042, Japan, kumamed1_2001@yahoo.co.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumagai
authors.forename: Eri
authors.initials: E
authors.lastname: Matsuki
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ohashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
authors.forename: Chikashi
authors.initials: C
authors.lastname: Yoshida
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wakita
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kozai
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shirasugi
authors.forename: Shin
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Iwase
authors.forename: Shingo
authors.initials: S
authors.lastname: Yano
authors.forename: Kaichi
authors.initials: K
authors.lastname: Nishiwaki
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakamaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069439:Dasatinib; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib