engleski

Follow-up of Pgp-related multidrug resistance in chronic myeloid leukemia (CML) patients undergoing Glivec therapy. The prognostic value of increased Pgp activity

BACKGROUND AND AIM: Although Glivec (imatinib mesylate, STI 571) represents successful treatment strategy in CML, some patients are inherently resistant or become resistant during the treatment. We monitored CML patients and observed that the changes in P-glycoprotein (Pgp)related multidrug resistance (MDR) might influence the response to Glivec treatment. Therefore, this long-term follow up study was undertaken 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-four adult patients with advanced CML (4 in BC, 12 in AP and 8 in CP) were monitored in 3 months intervals starting with July 2001. Previous treatment included HU and IFN alpha ; 2 patients received MDR-related therapy. Glivec was administered as oral monotherapy: 600 mg daily for BC and AP and 400 mg/day for CP, respectively. Due to toxicity reaction, the dose was reduced in 11 patients. 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: Central and peripheral myelogenous cells confirmed similar MDR status, Pgp-associated resistant cells were found both in BM and PB. Our results indicate the importance of longitudinal follow up of MDR status. 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 resistant and reactivated patients Pgp-related MDR is associated with chemoresistance to further therapy. In the absence of BM aspirate it is possible to assess Pgp phenotype and transport activity only on PB samples. Rh123 functional Pgp screening can be used as sensitive prognostic test and is particularly helpful in determination of Glivec-resistant phenotypes

Pgp; CML

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