title: Trough plasma imatinib levels are correlated with optimal cytogenetic responses at 6 months after treatment with standard dose of imatinib in newly diagnosed chronic myeloid leukemia.
abstract: To investigate the correlation of trough imatinib mesylate (IM) levels with cytogenetic or molecular responses, we measured trough IM levels in patients with chronic myeloid leukemia, chronic phase (CML-CP), at 6 months of treatment with a standard dose of IM. Eighty-seven newly diagnosed patients with CML-CP were prospectively enrolled. Seventy-eight patients (89.7%) showed an optimal response (complete or partial cytogenetic response) at 6 months. Trough IM levels were 1378 ± 725 ng/mL. When categorized into two groups, there was a statistically significant difference in numbers of patients with optimal and suboptimal responses at 6 months (group with  <1000: 80.6% vs. 19.4%;  ≥ 1000: 94.6% vs. 5.4%; p = 0.032), and in numbers of patients with early major molecular response (early-MMR) and without MMR at 6 months (group with  <1000: 3.2% vs. 96.8%;  ≥ 1000: 21.4% vs. 78.6%; p = 0.047). In conclusion, the incidence of optimal cytogenetic response or early-MMR in patients with CML-CP treated with IM for 6 months was significantly higher in those with a trough level of  ≥ 1000 compared with those with a level of <1000. Dose escalation of IM can be one option in patients with CML showing suboptimal response or resistance to the standard dose of IM, especially with low trough plasma IM levels (<1000 ng/mL).
authors.affiliation: Kyungpook National University Hospital, Jung-Gu, Daegu, Korea.
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Suk Joong
authors.initials: SJ
authors.lastname: Oh
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Hun Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Joo Seop
authors.initials: JS
authors.lastname: Chung
authors.forename: Young Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Soo Mee
authors.initials: SM
authors.lastname: Bang
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
authors.forename: Hong Ghi
authors.initials: HG
authors.lastname: Lee
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Won
authors.forename: Yoo Hong
authors.initials: YH
authors.lastname: Min
authors.forename: June Won
authors.initials: JW
authors.lastname: Cheong
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Ki Seong
authors.initials: KS
authors.lastname: Eom
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Moo Rim
authors.initials: MR
authors.lastname: Park
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.forename: Chul Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Hyeoung Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yeo Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Park
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Zang
authors.forename: Deog Yeon
authors.initials: DY
authors.lastname: Jo
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Seon Yang
authors.initials: SY
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001549:Benzamides; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl