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

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

Study of some prognostic factors in patients with aggressive non-hodgkin's lymphoma

The aim of this work was to study the serum level of soluble CD25 [sCD25], CD44 [sCD44] and [sCD95] as prognostic factors in the assessment of response to standard treatment protocols in patients with aggressive non-Hodgkin's lymphoma [NHL]]. Also, to correlate them with the known adverse prognostic markers of the disease. Twenty five patients with newly-diagnosed untreated aggressive NHL [REAL/WHO] and ten healthy age and sex-matched control subjects were enrolled in the study. The age of the patients ranged between 34 and 60 years with a mean of 48.6 +/- 8.1 years and the male to female ratio was 1.3:1. At presentation and just before administration of the fifth cycle of conventional CHOP regimen, all patients were subjected to: full history taking, through clinical examination, complete blood count [CBC], bone marrow aspiration/trephine biopsy, biochemical profile, activity markers assessment [erythrocyte sedimentation rate [ESR], serum lactate dehydrogenase [LDH], and beta-2 microglobulin [beta-2M]], imaging studies and estimation of serum sCD25, sCD44, and sCD95 by ELISA technique. The mean values of the three biological factors were significantly higher in pre-treatment samples as compared to the controls. However, there was a significant reduction in the mean values in the follow-up samples compared to the pre-treatment mean values. Patients who achieved complete response [CR] [48%] showed significantly lower mean values of sCD25, sCD44, and sCD95 than non-CR patients [32% with partial response [PR], and 20% with no response [NR]], both before and after therapy. Also, there were significant positive correlations between each of sCD25, sCD44, and sCD95 and other known adverse prognostic features such as age, advanced Ann Arbor stage, higher risk groups of age-adjusted International Prognostic Index [IPI], ESR, LDH, and beta-2M. Again, sCD25, sCD44, and sCD95 correlated positively with each other, Multivariate regression analysis showed that sCD25 [p<0.001], sCD44 [p<0.001], and sCD95 [p = 0.002] turned out to have independent prognostic value. Moreover, we could demonstrate cut off levels for the three biological markers; all patients presenting with values equal to or below these levels achieved CR [2325 pg/ml for sCD25, 540 ng/ml for sCD44, and 8650 pg/ml for sCD95]. In conclusion, the serum sCD25, sCD44, and sCD95 are independent prognostic factors that could predict disease outcome and response to standard CHOP regimen in patients with aggressive NHL. Measurement of these factors at diagnosis may improve prognostic factors models and serve as targets for therapy leading to better cure rate and reducing unnecessary toxicity