Longer Hydroxyurea Administration Prior to Imatinib Mesylate is Risk Factor for Unsuccessful Major Molecular Response in Chronic-Phase Chronic Myeloid Leukemia: Possibility of P-Glycoprotein Role

Document Type: Research Articles

Authors

1 Department of Internal Medicine Division of Hematology and Medical Oncology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

2 Department of Biochemistry, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

3 Department of Clinical Pathology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

4 Department of Clinical Pharmacology, Faculty of Medicine Universitas Indonesia-Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

5 Department of Internal Medicine Division of Hematology and Medical Oncology, Faculty of Medicine Universitas Diponegoro-Dr. Karyadi Hospital, Semarang, Indonesia.

Abstract

Objective: This study aimed to identify the association between duration of HU administration prior to IM treatment and MMR achievement in chronic-phase CML while evaluating the role of MDA, HIF-1α and P-gp. Methods: The study was conducted at Dr. Cipto Mangunkusumo National General Hospital and Dharmais Cancer Hospital, Jakarta using retrospective cohort design to analyse the association between the duration of HU before IM and its MMR achievement and cross-sectional design to analyse the association between MDA, HIF-1α and P-gp expressions with MMR achievement. Main subjects were chronic-phase CML patients treated by HU prior to IM for ≥ 12 months and HU only. The subjects were divided into four main groups: (1) chronic-phase CML patients treated with HU ≤ 6 months + IM ≥ 12 months and (2) HU > 6 months + IM ≥ 12 months (3) HU only (≤ 6 months), (4) HU only ( >6 months). Subjects were obtained from January 2015 to May 2016. Data were gathered through history taking, physical examination, medical record evaluation, and blood sample analysis. Bivariate analysis was conducted using chi square, independent T-test, and Mann-Whitney according to the variables. Results: Administration of HU for more than 6 months prior to IM was associated with unsuccessful MMR achievement (RR 1.60; 95%CI 1.29-2.00). MDA level, HIF-1α, P-glycoprotein expression were not associated with MMR achievement but the mean MDA level (0.63±0.31 vs 0.75±0.41 p=0.461) and median P-glycoprotein expressions {16,92 (0,04 – 43,86) vs. 5,15 (0,02–39,64); p=0.311} were found to be higher in patients receiving HU for > 6 months group than in HU ≤ 6 months group consecutively. Conclusion: Administration of HU for more than 6 months prior to IM was associated with unsuccessful MMR achievement in chronic-phase CML. The study suggested that P-glycoprotein overexpression as the predictor for unsuccessful MMR achievement.

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