Biochemia Medica, Vol. 19 No. 1, 2009.
Original scientific paper
Monitoring chronic myeloid leukemia patients responding to treatment with tyrosine kinase inhibitors by real-time quantitative polymerase chain reaction
Margareta Radić Antolic
; Clinical Institute of Laboratory Diagnosis, Zagreb University Hospital Center, Zagreb, Croatia
Renata Zadro
orcid.org/0000-0003-1590-0514
; Clinical Institute of Laboratory Diagnosis, Zagreb University Hospital Center, Zagreb, Croatia
Dubravka Sertić
; Department of Hematology, University Department of Medicine, Zagreb University Hospital Center, Zagreb, Croatia
Boris Labar
; Department of Hematology, University Department of Medicine, Zagreb University Hospital Center, Zagreb, Croatia
Abstract
Introduction: Historically, many revolutionary advances in therapy for chronic myeloid leukemia (CML) have been achieved over time, among them most important being imatinib mesylate (IM). More precise assessment of response to therapy with IM and an accurate measure of the degree of BCR-ABL transcript reduction can be achieved by using real-time quantitative polymerase chain reaction (RQ-PCR).
Aim: To quantitate BCR-ABL transcripts in CML patients and to monitor response to treatment with tyrosine kinase inhibitors.
Materials and methods: The study included a 31 patients treated with IM. RQ-PCR was performed according to the Europe Against Cancer protocol, with ABL as a housekeeping gene. BCR-ABL/ABL ratio was calculated. Patients were divided into groups according to the European Leukemia Net criteria for achievement of major molecular response (MMoR). Group I consisted of 11 patients with more than 3 log reduction, group II consisted of 13 patients with less than 3 log reduction, and group III included 7 patients with a follow up of less than 18 months.
Results: Group I patients achieved MMoR with detectable or undetectable BCR-ABL transcript in a period of 2 years of follow up and fulfilled the criteria for favorable long term prognosis. Group II patients never achieved MMoR with IM and required different therapy approach, higher dose of the same tyrosine kinase inhibitor or a second generation drug. Seven newly diagnosed CML patients from group III were monitored for less than 18 months and therefore MMoR could not be estimated. Using the same analogy as in the first two groups, prediction of the course of disease could be possible.
Conclusion: Study results show that RQ-PCR is mandatory for careful monitoring of therapeutic response to tyrosine kinase inhibitors in order to ensure that an individual patient receives proper treatment and to decide whether and when therapy should be changed.
Keywords
chronic myeloid leukemia; imatinib mesylate; quantitative polymerase chain reaction; major molecular response
Hrčak ID:
32260
URI
Publication date:
5.2.2009.
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