Prognostic Assessment of P-Glycoprotein over Expression in Refractory and / or Relapsed Acute Myeloid Leukemia and Response to Cyclosporine A
Ashraf M. El Hefni1, Fouad M. Abu Taleb1, Khaled M.Hadhoud1, Mahmoud A. Ashour1 and Amal Ahmed Zidan2
1Hematology &Medical Oncology Unit, Internal Medicine Department
2ClinicalPathology Department, Faculty of Medicine, Zagazig University
Abstract: Acute myeloid leukemia (AML) is a malignant hematopoietic neoplasm characterized by clonal proliferation of tumor cells that arise from the hematopoietic stem/progenitor population within the bone marrow. Objectives our study was enrolled to assess p-glycoprotein overexpression in refractory and /or relapsed acute myeloid leukemia and response to addition of cyclosporine A to chemotherapy. Patients and Methods this study was carried out at Hematology and Medical Oncology Unit, Internal Medicine Department, Zagazig University hospital during the period between July 2010 and July 2011. Forty patients with refractory or relapsed acute myeloid leukemia were classified into two groups, group (A): included 20 adult patients, their ages ranged from 18 to 60 years with median age 39 years, and they were treated with chemotherapy alone, group (B) included 20 adult patients with, their ages ranged from 20 to 61 years with median 40 years, they were treated with oral cyclosporine A in addition to the same chemotherapy protocol given in group A. All patients subjected to thorough medical history, physical examination, routine laboratory and radiological investigations and flowcytometry to assess p-glycoprotein overexpression. All patients had severe cardiac, pulmonary, hepatic, renal, neurological, metabolic disease, concomitant malignancies or uncontrolled infections were excluded from the study .Results P-glycoprotein was overexpressed in 22 patients with refractory or relapsed AML (55%), when the unpaired (t) test was applied to test the significance of difference between the mean value ± S.D of percentage of bone marrow blasts and Pglycoprotein overexpression, there was not any significant difference detected (t=0.08 and p=0.91). Chi square test (χ2) test was applied to test the significance of difference among different variables and P-glycoprotein overexpression. A statistically significant difference was found with cytogenetic study (Χ2 =8.5 and P=0.03) and response to treatment (Χ2 =8.02 and P=0.018). 13 patients were achieved CR (33%), 8 patients with PR (20%) and 19 patients with NR (47%) and when Chi square (χ2) test was applied to test the significance of difference among variables associated with response to treatment, a high significant difference was found with cytogenetic study (Χ2 =33.93 and P= 0.001) The mean overall survival in group B was more than group A but wasn't significantly different (P= 0.25) also no significant difference between overall survival and P-glycoprotein overexpression (P= 0.15), but there was highly significant difference between overall survival and response to treatment (P= 0.0014), also Chi square (χ2) test was applied to test the significance of difference among different toxicities which were occurred during therapy with patient groups, there is no significant difference was found conclusion P-glycoprotein was overexpressed in 55% of patients with refractory or relapsed acute myeloid leukemia and provide prognostic indicator for response to treatment and addition of oral cyclosporine as P-glycoprotein modulator doesn't improve response to chemotherapy or overall survival.
[Ashraf M. El Hefni, Fouad M. Abu Taleb, Khaled M.Hadhoud, Mahmoud A. Ashour and Amal Ahmed Zidan. Prognostic Assessment of P-Glycoprotein over Expression in Refractory and / or Relapsed Acute Myeloid Leukemia and Response to Cyclosporine A. Life Sci J 2013;10(1):1427-1436] (ISSN:1097-8135).http://www.lifesciencesite.com. 3
Key words:- Acute myeloid leukemia (AML), P-glycoprotein (Pgp),Treatment response.