Studies on biomarkers for oxidative stress in patients with chronic myeloid leukemia

Chronic myeloid leukemia [CML] is a myeloproliferative disorder with a unique genetic rearrrangement, the Philadelphia chromosome. High reactive oxygen species [ROS] levels favor oxidative stress, which could play a vital role in normal processes and various pathophysiologies including neoplasm. Biomarkers of oxidative stress are measured as products of oxidized proteins and lipids. Plasma levels of protein carbonyl [PC], thiobarbituric acid reactive substances [TBARS] and total lipid hydroperoxide [LOOH] were used as biommarkers of oxidative stress in the past. The aim of this study was to evaluate the products of protein oxidation and lipid peroxidation in plasma as biomarkers of oxidative stress in CML patients. The study included 40 CML patients and 20 age- and sex-matched healthy voluntteers. Of 40 CML patients, 28 were in chronic phase [CML-CP] and 12 in accelerated phase [CML-AP]. Plasma levels of PC, TBARS and LOOH as biomarkers of oxidative stress were evaluated by spectrophotometric methods. There were significant differences [P<.05] in plasma levels of PC, TBARS and LOOH in CML, CML-CP and CML-AP patients as compared to controls. PC, TBARS and LOOH might reflect oxidative stress in CML patients and might be used as biomarkers in such patients

S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia

The functional definition of aplastic anemia [AA] is the failure of hematopoietic stem cells to proliferate. The aim of the present study was to analyze the S-phase fraction [SPF] [proliferative activity] in patients with AA at diagnosis to explore its relationship with disease characteristics and its value in discriminating among patients with different prognoses. We also investigated whether the SPF value influenced the response to immunosuppressive therapy in AA patients. The analysis of SPF at the time of diagnosis was carried out by flow cytometry on peripheral blood samples from 53 consecutive patients with AA and 30 age- and sex-matched controls. All patients were given cyclosporine and followed up periodically to determine response to therapy. Based on the median SPF, AA patients were divided into two groups: patients with SPF <0.59% [n=27] and patients with SPF >0.59% [n=26]. An SPF >0.59% was associated with advanced age [P=.02] and elevated serum LDH level [P=.01]. Patients with an SPF >0.59% also had a higher incidence of paroxysmal nocturnal hemoglobinuria and cytogenetic abnormalities. During a median follow-up of 18 months, 3.7% of patients with SPF <0.59 and 11.5% of patients with SPF >0.59% developed dysplasia and one patient with SPF >0.59% converted into AMI. A significantly higher [P=.018] overall response rate of 53.9% was found in patients with SPF >0.59% versus 22.2% of patients with SPF <0.59% at 6 months. Independently of the peripheral blood count, the SPF at diagnosis may provide information on the expected response to immunosuppressive therapy and the propensity for disease to evolve into MDS/AML. Hence, SPF may serve as an early indicator for the evolution of MDS/AML in patients with AA and thus contribute to therapeutic decisions