title: Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plasma levels and major molecular response.
abstract: Despite the prognostic value of trough imatinib plasma levels (IPL) identified in some studies, no recommendations for the use of IPL results in routine management of CML patients have been issued. We report two patients in whom daily imatinib dose was increased from 400 to 600 or 800 mg because of low IPL found at various intervals from the beginning of treatment (7 measurements; mean IPL values = 616.33 and 764.5 ng/mL, respectively). Both patients achieved suboptimal response according to the European LeukemiaNet criteria (complete cytogenetic response was not achieved after 1 year of treatment in patient 1 and major molecular response after 47 months of standard-dose imatinib therapy in patient 2). In addition, we have demonstrated low hOCT-1 expression at diagnosis in both patients, retrospectively. Escalation of imatinib daily dose resulted in a significant increase of IPL (6 measurements; mean = 1790 and 1416.66 ng/mL, respectively) and in the achievement of complete cytogenetic response in patient 1 after 3 months and major molecular response within 15 and 6 months in both patients. Our cases demonstrate that low IPL identified at various non-predefined intervals from the beginning of therapy may be used for deciding on dose escalation in selected CML patients in the routine clinical setting, especially in cases with suboptimal treatment response.
authors.affiliation: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, University Palacky in Olomouc, Faculty Hospital Olomouc, IP Pavlova 6, 775 20, Olomouc, Czech Republic. edgar.faber@fnol.cz
authors.forename: Edgar
authors.initials: E
authors.lastname: Faber
authors.forename: David
authors.initials: D
authors.lastname: Friedecký
authors.forename: Katerina
authors.initials: K
authors.lastname: Micová
authors.forename: Martina
authors.initials: M
authors.lastname: Divoká
authors.forename: Beata
authors.initials: B
authors.lastname: Katrincsáková
authors.forename: Sárka
authors.initials: S
authors.lastname: Rozmanová
authors.forename: Marie
authors.initials: M
authors.lastname: Jarosová
authors.forename: Karel
authors.initials: K
authors.lastname: Indrák
authors.forename: Tomás
authors.initials: T
authors.lastname: Adam
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D001549:Benzamides; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D027702:Organic Cation Transporter 1; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate