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2.
Cancer Genet Cytogenet ; 174(2): 111-5, 2007 Apr 15.
Article in English | MEDLINE | ID: mdl-17452251

ABSTRACT

The molecular hallmark of CML is the BCR-ABL fusion gene, usually with specific breakpoints within ABL intron 1 and BCR introns b2, b3, and e19. The amplification of the BCR-ABL hybrid gene resulting from additional copies of the Ph chromosome has been identified as a mechanism for imatinib (IM) resistance. Cytogenetic clonal evolution correlates with the accelerated phase of leukemia, whereas deletions in the derivative chromosome 9 are associated with a poor prognosis. Relevance in IM therapy is unclear. We report a case of a 39-year-old male with chronic phase CML. Cytogenetic studies showed a complex karyotype with additional copies of the Ph chromosome, sextasomy 8, and ASS gene deletion. An unusual aberrant fusion gene product was derived from the joining of BCR exon 13 (b2) and ABL exon 3 (a3). During IM treatment, the patient was monitored in 3- to 6-month intervals. Major cytogenetic response was achieved after 5 months; complete cytogenetic and molecular remission was reached after 8 months; after 22 months, normal karyotype and absence of the BCR-ABL product continued. Our data seem to confirm the data of others in regards to the b2a3 breakpoint, suggesting a better prognosis, regardless of other unfavorable factors.


Subject(s)
Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Antineoplastic Agents/therapeutic use , Benzamides , Chromosome Aberrations , Chromosome Banding , Humans , Imatinib Mesylate , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Philadelphia Chromosome , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Remission Induction , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic , Treatment Outcome
4.
Pol Arch Med Wewn ; 115(6): 535-44, 2006 Jun.
Article in Polish | MEDLINE | ID: mdl-17263225

ABSTRACT

UNLABELLED: Targeted therapy with the use of imatinib mesylate is a recognized option for patients with chronic myeloid leukemia (CML) not eligible for allogeneic hematopoietic cell transplantation. We present results of a multicenter phase II study on the use of imatinib in chronic phase after failure to interferon-alpha (IFN-alpha). Sixty patients (27 female, 33 male), median age 46 (range, 21-64), were included with hematologic relapse (n= 11), hematologic refractoriness (n=4), cytogenetic relapse/ /+65resistance (n=40) or intolerance to IFN-alpha (n=5). The median time from CML diagnosis was 39 months (range, 4-132), the median time of IFN-alpha therapy equaled 23 months (range, 1-78). Imatinib mesylate was administered at a dose of 400 mg/day for 1 year. In patients who achieved major cytogenetic response (MCR) the therapy was continued until progression. Thirty-three (55%) patients achieved MCR after one year of treatment. At 4 years the cumulative incidence of complete cytogenetic response equaled 40% (95% CI, 29-56). Among 27 patients who did not achieve MCR at 12 moths, in 12 cases the study course was discontinued prematurely because of blast crisis (n=9), prolonged neutropenia (n=l), severe transaminases elevation (n=l) or incidental death not related to the study drug or disease (n=l). The probability of OS at 4 years equaled 82% (95% CI, 72-91) and was lower for patients with the disease duration >36 months and those with Sokal index > or =0.8. Among patients who achieved MCR, the probability of progression-free survival was 78% (95% CI, 69-85). Time to progression (cytogenetic, n=6; blast crisis, n=l) varied from 3-36 months. CONCLUSIONS: Imatinib mesylate is characterized by good tolerance and allows achieving cytogenetic response in more than half of late chronic phase CML patients with failure of interferon therapy. However, the progression rate is substantial, which raises concern regarding the curative potential of monotherapy with imatinib in this group of patients.


Subject(s)
Interferon-alpha/therapeutic use , Leukemia, Myeloid, Chronic-Phase/drug therapy , Piperazines/administration & dosage , Piperazines/adverse effects , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Adult , Benzamides , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Humans , Imatinib Mesylate , Leukemia, Myeloid, Chronic-Phase/mortality , Leukemia, Myeloid, Chronic-Phase/pathology , Male , Middle Aged , Remission Induction/methods , Treatment Failure , Treatment Outcome
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