Author/Editor		Glaser, Marjana; Grmek-Zemljič, Tatjana; Borin, Peter
Title		Naše izkušnje pri zdravljenju kronične mieloične levkemije z imatinib mesilatom
Translated title		Our experience in treatment of chronic myeloid laukemia with imatinib mesylate
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 73, št. 4
Publication year		2004
Volume		str. 207-10
Language		slo
Abstract		Background. Chronic myeloid leukemia is a clonal disease of hematopoietic stem cell which progresses through three phases. During progression, leukemic cells become therapy resistant and patients die of acute leukemia. Disease specific is the presence of Philadelphia chromosome, the result of reciprocal translocation between the chromosomes 9 and 22. The molecular consequence of this translocation is the BCR-ABL fusion protein with tyrosine kinase activity which induces malignant transformation to leukemia. Imatinib mesylate (Glivec) is the first sintetised drug with tyrosine kinase blocking activity. Patients and results. We represent 9 patients with chronic myeloid leukemia who were treated with imatinib from 2000 till now. Three of them were in chronic phase, two in accelerated phase and four in blast crysis. The average age was 59 years while the average time from the disease onset till imatinib treatment was 57.77 months. All of them were previous treated with interferon and/or hydroxyurea. The initial dose of imatinib was 600 mg. The patients were treated from the period ranging from 2.5 till 28 months. Three of them in chronic phase showed complete cytogenetic, two in blastic phase partial cytogenetic remission and all of them showed complete hematologic remission. Four patients in blastic crysis died during the therapy. Seven of them showed mild side effects. Conclusions. Imatinib binds to the ATP binding site on BCR-ABL fusion protein and inhibits the phosphorilation of substrate and subsequent by inhibits malignant cell transformation. The drug is active in all three phases of the disease. In addition, it inhibits also platelet derived growth factor and c-KIT. However it is inactive against other tyrosine kinases. Imatinib is now treatment of choice in all patients in chronic phase of the disease and is in clinical testing in patients in transplantation programme. (Abstract truncated at 2000 characters).
Summary		Izhodišča. Kronična mieloična levkemija je klonska krvna rakava bolezen, ki poteka skozi tri obdobja, v katerih postajajo levkemične celice vse bolj odporne na zdravljenje, zato bolniki umrejo s sliko akutne levkemije. Za bolezen značilno se pojavi kromosom Philadelphia, ki je posledica translokacije dolgih krakov kromosomv 9 in 22. Molekulna posledica translokacije je nastanek fuzijskega proteina BCR-ABL, ki ima lastnosti encimatirozin kinaze in povzro i maligno preobrazbo v levkemijo. Imatinib mesilat (Glivec) je prvo sintetizirano zdravilo, ki ustavi delovanje tega encima. Bolniki in rezultati. Prikazanih je 9 bolnikov s kronično mieloično levkemijo, ki so bili zdravljeni z imatinibom od leta 2000 do sedaj. Trije bolniki so bili v kronični fazi, dva v pospešeni in tirje v blastni preobrazbi. Povprečna starost bolnikov je bila 59 let, povprečni čas trajanja od ugotovitve do zdravljenja z imatinibom pa 57,75 meseca. Vsi bolniki so bili prej zdravljeni z interferonom in/ali hidroksiureo. Začetni odmerek imatinaba je bil 600 mg. Bolniki so bili zdravljeni od 2,5 do 28 mesecev. Pri treh v kronični fazi smo ugotovili popoln citogenetski odgovor, pri dveh v blastni preobrazbi delni citogenetski odgovor, pri vseh pa hematološki odgovor. Štirje bolniki v blastni preobrazbi so v času zdravljenja umrli. Sedem bolnikov je imelo blage stranske učinke zdravljenja. Zaključki. Imatinib se veže na vezavno mesto za ATP na BCR-ABL fuzijskem proteinu. Na ta način prepreči fosforilacijo substrata in zaustavi maligno transformacijo celic. Zdravilo deluje v vseh treh fazah bolezni, ni pa specifično. Blokira tudi delovanje c-KIT in iz trombocitov izhajajoči rastni faktor, ne pa drugih kinaz. Imatinib je sredstvo izbire pri vseh bolnikih z novo ugotovljeno kronično obliko bolezni, v kliničnem testiranju pa je tudi njegova uporaba pred presaditvijo krvotvornih matičnih celic. (Izvleček prekinjen pri 2000 znakih).
Descriptors		LEUKEMIA, MYELOID, CHRONIC PHILADELPHIA CHROMOSOME PROTEIN-TYROSINE KINASE MESYLATES TREATMENT OUTCOME