Study of P-glycoprotein [multi-drug resistance gene] expression in acute lymphoblastic leukemia in the elderly: correlation with cytogenetics and response to induction chemotherapy

ABSTRACT

Elderly patients with acute lymphoblastic leukemia [ALL] have only rarely been included in clinical trials. The aim of this work was to investigate some of the biologic characteristics of ALL in the elderly by cytogenetic analysis and by studying of P-glycoprotein [P-gp] or multidrug resistance [MDR-1] protein expression at initial presentation. Twenty patients with newly-diagnosed beta-lineage ALL were accrued to the study. They were divided into two groups; group I ten patients aged <60 years, and group II ten patients aged >/= 60 years. They were subjected to history taking, clinical examination, complete blood count [CBC] and bone marrow [BM] aspiration with immunophenotyping to establish the diagnosis. Cytogenetic analysis was done by the G-banding technique and estimation of P-gp in ALL blast cells was performed by flow cytometry. All patients were in a good performance status and induction chemotherapy was instituted according to standard protocol for ALL. Complete remission [CR] was achieved in 50% of patients in group I and 40% in group II. No significant difference was found between the two groups regarding P-gp expression in pretreatment samples. However, a highly significant difference was noted on comparing CR and non-CR patients in both groups as regards P-gp expression [t=20.89, p=0.00]. Cytogenetic analysis revealed that 20% of patients in group I and 60% of cases in group II had cytogenetic abnormalities. No significant difference was found between CR and non-CR patients as regards the cytogenetic status. Also, there was no significant difference between patients with normal and those with abnormal karyotypes as regards P-gp expression. Failure to respond to chemotherapeutic drugs in ALL in the elderly seems to be a multifactorial phenomenon. Further clinical trials evaluating the disease features, outcome, and new therapeutic approaches are warranted