5.1. ChronicMyeloid Leukemia Reciprocaltranslocation of 9 and 22 philadelphia chromosome causes the BCR-ABL fusionprotein which results in leukemogenesis. When imatinib is used, significant andrapid inhibition of this protein is observed, thus imatinib is used fortreatment of CML.
When it is compared with interferon-alpha (INF-?) forpatients, imatinib reduced the hematological response with the 95.3% andcytogenetic response was found as 73.8%. When MMR (major molecular response)and progression-free survival (PFS) is investigated 60 months following, 97%PFSfor 12 months and 89% PFS for 60 month is reached.
Better results are obtainedfrom early molecular response as predicted. Despite all the successful results,resistance to imatinib is a major problem. When the patients are examined,initial responses are lower in advanced-phase disease and responses were nonpermanent.Primary resistance is described as inability to reach CHR at 3 months and MCRat 6 months. The reason for that can be differential drug metabolism or drugtransport. 45.
2. Gastrointestinal Stromal TumorsIt is result of mesenchymal neoplasms of the GI tract. Expression ofc-KIT in tumor cells activating KIT mutations and PDGFRA mutations. Imatinibhas reducing effect on this disease and inhibits tyrosine kinase activity ofKIT. There is also positive effect on the treatment of unrespectable ormetastatic GIST. For this disease different dosing regimens are examined with746 patients and there is no significant difference between 800 mg and 400 mgdrug dosing for healing. The similar results are obtained for both two dosageboth progression-free survival and overall survival.
45.3. Philadelphia Chromosome-positive AcuteLymphoblastic Leukemia Adult ALL patients has an abnormality on Philadelphiachromosome. It is a new diagnosis for ALL and it is age dependent disease, withincreasing age it gives unfavorable prognosis.
It differs from CML as thedifferent sized proteins caused by the abnormality of Philadelphia chromosomewhich has translocation on 9 and 22 chromosomes. The result of thistranslocation is producing fusion gene which express highly BCR-ABL and it endsup different sized p190 and p210 proteins. While CML cases generally producep210 predominantly, ALL patients synthesize Ph-positive p190 protein. Imatinibis a promising treatment strategy for ALL patients also.