ABSTRACT
The use of imatinib mesylate (Glivec) (Novartis Pharma AG, Switzerland) that is the drug of choice in treating patients with chronic myeloid leukemia (CML) has increased 7-year survival and improved the prognosis of the disease. The drug is generally tolerated well; the proportion of patients in whom imatinib treatment results in the development of toxic complications is small. Drug-induced interstitial pneumonitis associated with imatinib therapy is a rare complication that requires timely differential diagnosis, discontinuation of an inductor (imatinib), and altered further treatment policy.
Subject(s)
Antineoplastic Agents/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Lung Diseases, Interstitial/chemically induced , Piperazines/adverse effects , Pyrimidines/adverse effects , Aged , Antineoplastic Agents/therapeutic use , Benzamides , Diagnosis, Differential , Female , Humans , Imatinib Mesylate , Lung Diseases, Interstitial/diagnostic imaging , Piperazines/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/therapeutic use , Tomography, X-Ray ComputedABSTRACT
AIM: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK). MATERIAL AND METHODS: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand--investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made. RESULTS: The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients. CONCLUSION: Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.
Subject(s)
Bone Marrow Cells/drug effects , Chromosomes, Human, Pair 8/genetics , Fusion Proteins, bcr-abl/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Philadelphia Chromosome/drug effects , Protein Kinase Inhibitors/therapeutic use , Trisomy , Adult , Benzamides , Bone Marrow Cells/enzymology , Bone Marrow Cells/pathology , Drug Administration Schedule , Female , Humans , Imatinib Mesylate , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , Piperazines/administration & dosage , Piperazines/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Time FactorsABSTRACT
AIM: To analyse resistance to imatinib therapy, efficacy and safety of dasatinib. MATERIAL AND METHODS: A total of 18 patients with chronic myeloid leukemia (CML) in a chronic stage received dasatinib for 9-30 months (median 30 months) to September 2008. RESULTS: Lethal outcomes during dasatinib treatment were absent. To September 2008, 16 (89%) patients were alive, 2 (11%) patients died of the disease progression after dasatinib discontinuation. A complete clinicohematological response was observed in all the patients. Major cytogenetic, complete cytogenetic, major molecular, complete molecular responses were achieved in 12 (67%), 10 (55%), 7 (39%) and 5 (28%) patients, respectively. Hematological and non-hematological toxicity occurred in 9 (50%) patients. Now 12 (67%) patients continue dasatinib treatment, in 6 (33%) patients the drug was discontinued. CONCLUSION: The results from trials in Russian Hematological Research Center are the same as in the international study. Dasatinib is effective and well tolerated therapeutic option for imatinib-resistant patients with a chronic phase of CML.
