Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progression.

Abstract

BACKGROUND AND OBJECTIVES:

The acquisition of additional cytogenetic changes (clonal evolution, CE) during treatment of chronic myeloid leukemia (CML) with imatinib mesylate is currently regarded as an index of increasing resistance to imatinib. Therefore, to investigate whether CE as an isolated event increases the risk of disease progression during imatinib treatment, we compared the outcome of patients with CML in chronic phase (CML-CP) who developed CE whilst in complete hematologic remission with the outcome of comparable patients in complete hematologic remission who showed no evidence of CE.

DESIGN AND METHODS:

We serially studied cytogenetic findings in 102 patients receiving the Abl-tyrosine kinase inhibitor, imatinib mesylate, as sole agent to treat CML-CP who had no evidence of CE before initiation of imatinib treatment.

RESULTS:

CE was identified during treatment with imatinib in 15 patients, 10 of whom were in complete hematologic remission. In most cases these changes occurred exclusively in the Ph+ population but in three patients additional changes occurred in a co-existing Ph-negative population. Patients with de novo CE in the absence of any other sign of disease progression had a significantly higher incidence of progression by 18 months than did non-CE patients (progression-free survival 34.3% (CI 10.5-69.8%) vs. 94.1% (CI 80.6-98.4%), p<0.0001).

INTERPRETATION AND CONCLUSIONS:

Based on this relatively small series of patients, we conclude that acquisition of clonal evolution increases the risk of subsequent disease progression also in CML patients in complete hematologic remission on imatinib.

• Authors: Sarah Marktel, David Marin, Nicola Foot, Richard Szydlo, Marco Bua, Anastasios Karadimitris, Valeria A S De Melo, Paul Kotzampaltiris, Francesco Dazzi, Amin Rahemtulla, Eduardo Olavarria, Jane F Apperley, John M Goldman
• Journal: Haematologica (Haematologica) Vol. 88 Issue 3 Pg. 260-7 (Mar 2003) ISSN: 0390-6078 [Print] Italy
• PMID: 12651263 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adolescent
• Adult
• Aged
• Benzamides
• Chromosome Aberrations
• Clone Cells (pathology)
• Cytogenetic Analysis
• Disease Progression
• Drug Resistance, Neoplasm (genetics)
• Female
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (diagnosis, drug therapy, pathology)
• Male
• Middle Aged
• Piperazines (therapeutic use)
• Prognosis
• Pyrimidines (therapeutic use)