engleski

Clinical value of assessment the changes of P glycoprotein related multidrug resistance in CML patients undergoing Imatinib mesylate therapy

BACKGROUND: Development of imatinib mesylate (Glivec, Novartis, Basel, Switzerland) is an important advance in the management of chronic myeloid leukemia (CML). However, some patients become resistant during the treatment and some are even inherently resistant to imatinib. Its long-term unsuccessful use may ruin chances of resistant patients to benefit from alternative therapies. Therefore it is important to predict the responsiveness among patients thus allowing them to get the most adequate treatment. AIM: To assess in a long-term follow- up study the changes in P-glycoprotein (Pgp)related multidrug resistance (MDR) in CML patients undergoing imatinib therapy, to estimate the occurrence of MDR in CML patients, and to determine the correlation of Pgp expression and activity to the treatment outcome. METHODS: Twenty-eight adult patients with advanced CML (5 in blast crisis (BC), 10 in accelerated phase (AP) and 13 in chronic phase (CP)) were monitored in 3 months intervals starting with July 2001. Previous treatment included mostly HU and IFN alpha ; 6 patients received MDR-related therapy. Imatinib was administered as oral therapy: 600 mg/day for BC and AP and 400 mg/day for CP, respectively. Bone marrow (BM) and peripheral blood (PB) cells were examined using flow cytometry. Pgp phenotype was analysed in anti HLA-DR/Pgp combination and Pgp activity was measured in Rhodamine dye (Rh123) functional efflux assay. RESULTS: Among 28 patients, 9 died, 8 relapsed and 2 were refractory. Central and peripheral myelogenous cells confirmed similar MDR status ; Pgp-associated resistant cells were found both in BM and PB. Most of the patients achieving hematologic remission showed stable Pgp activity, whereas in those who underwent clinical relapse and died the tendency of Pgp activity increase was observed. CONCLUSION: In the absence of BM aspirate it is possible to assess Pgp phenotype and transport activity only on PB samples. Our results showed that longitudinal follow up of Pgp-related MDR status could detect resistant patients which might be crucial for their further treatment. As increased Pgp-related MDR activity can be associated with chemoresistance to imatinib therapy, Pgp-related MDR screening may become a prognostic tool of important clinical value for detecting imatinib-resistant patients

Pgp; Imatinib mesylate; CML

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