Role of granulocyte colony stimulating factor (G-CSF) in chemotherapy induced neutropenia.

BACKGROUND: In the past decade, there have been many clinical trials investigating the potential benefits of adjunctive therapy with colony stimulating factors (CSFs) both to ameliorate or prevent profound neutropenia and its potentially life threatening consequences. Neutropenia is the most common dose limiting side effects of cytotoxic chemotherapy. We decided to study the effect of same in our patients coming to haematology clinic. AIMS AND OBJECTIVES: To see the effect of G-CSF on severity of neutropenia following chemotherapy in patients of haematological malignancies and to see the effect of G-CSF on duration of hospitalization, documented infections and duration of fever as compared to control group in patients with neutropenia following chemotherapy in haematological malignancies. MATERIAL AND METHODS: Thirty patients of acute leukemia were prospectively studied. Patients were given G-CSF 24.hours following chemotherapy induced neutropenia and following parameters were observed. (a) median time to ANC recovery (b) incidence and duration of fever (c) duration of hospitalization following chemotherapy (d) incidence of documented infections. The patients were given G-CSF until the neutrophil count was >1000/ml for 3 days or maximum of 7 days. RESULTS: Mean age was 29.33 +/- 14 years in G-CSF group and 27.53 +/- 13.75 in control group. Mean duration of neutropenia was 11.4 days (p < 0.05) in G-CSF group and 15.8 days in control group. Mean duration of fever was 8.2 days in G-CSF group and 13.53 days in control group (p < 0.05). Mean duration of hospital stay was 21.33 days in G-CSF group and 25 days in control group (p > 0.05). CONCLUSIONS: The study demonstrates that G-CSF administration is efficacious in chemotherapy induced neutropenia by decreasing the duration of neutropenia and duration of fever.

Plasma concentrations of lipid peroxidation products in children with acute leukaemia.

Acute leukaemia is the most common childhood malignancy. The cause of leukaemia is not known in most of the cases and of late free radicals have been implicated in the pathogenesis of leukaemia. The degree of lipid peroxidation was studied in the present study as a marker of disease activity in 15 patients of acute lymphoblastic leukaemia and 20 healthy age and sex matched individuals served as control. Serum malonaldehyde (MDA) levels were increased in leukaemia and were higher in the active phase of disease as compared to those in remission, Hence, serum MDA estimation in leukaemia can be of help in diagnosis and to predict the chances of relapse.

Role of oxygen free radicals in shock.

AIMS OF THE STUDY: To study lipid peroxidation, magnesium levels (Mg) in plasma and red cells (RBC), superoxide dismutase (SOD) and catalase (CAT) activities in the plasma and RBC of shock patients. METHODOLOGY: Twenty five patients with clinically defined septic shock and 30 healthy volunteers were selected for the study to study the parameters of oxidative stress. RESULTS: Septic shock patients had higher activities of plasma and RBC SOD and CAT activities as compared to control. Also, plasma Mg and malonaldehyde (MDA) levels were higher in shock patients as compared to controls. While, RBC Mg levels were similar in two groups. CONCLUSIONS: The finding of increased concentration of MDA, Mg, SOD and CAT in sepsis implicates oxygen free radicals in the pathophysiology and free radical scavengers may have a role in organ preservation.

Oxidative stress after acute myocardial infarction: effect of thrombolytic treatment.

OBJECTIVE: Treatment with thrombolysis plays a crucial role in salvaging the myocardium in myocardial infarction (MI) patients, but reperfusion of ischaemic areas may itself be associated with reperfusion injury mediated by free radical induced oxidation. Hence the present study was planned to evaluate oxidative stress in patients receiving thrombolytic therapy during MI and to compare them with those not receiving thrombolysis. METHODS: Thiobarbituric acid reactive substance (TBARS) was used as a marker of lipid peroxidation in 30 patients after acute MI. Thirteen were treated by intravenous thrombolysis and 17 served as control. Also, vitamin E levels were estimated in these patients. RESULTS: Patients treated with thrombolysis showed a fall in vitamin E and increase in TBARS within first hours. The decrease in vitamin E was independent of a change in cholesterol. However, the levels were similar at 72 hours. CONCLUSION: The results indicate increased free radical production after MI and reperfusion also increases in free radical production and antioxidants may have a part in improving thrombolytic reperfusion of ischaemic myocardium.

Glutathione levels in health and sickness.

We speculate that the glutathione (GSH) status of human subjects could be an indicator of health and functional age. In this regard, in a study in which, 80 young and 40 elderly healthy individuals were selected as control. We also studied 145 patients with chronic illnesses namely, ischaemic heart disease, diabetes, preeclampsia, cataract, chronic renal failure and leukaemia (age 52 +/- 8.6 years). We observed that all the subjects had high malonadildehyde and low glutathione levels as compared to control. These early observations support the hypothesis that oxidative stress may have an important aetiological rule and antioxidants a potential therapeutic role.

Serum vitamin E in chronic myeloid leukaemia.

OBJECTIVE: Experimental evidence suggests that free radicals can participate in tumour promotion and malignant conversion and free radical scavengers like alphatocopherol act as first line of defense against peroxidation of polyunsaturated fatty acids. The present study was planned to estimate serum vitamin E levels in patients of chronic myeloid leukaemia (CML). METHODS: Serum vitamin E levels were estimated in 25 CML patients before and after the treatment. Twenty five age and sex matched healthy individuals served as control. RESULTS: Mean serum vitamin E levels were significantly decreased in CML patients before starting the treatment as compared to control. Also, vitamin E levels increased significantly after the treatment, but, remained lower than the control. CONCLUSION: Vitamin E levels were lower in CML patients as compared to control and the levels increased significantly after treatment in these patients. This could be due to decrease in oxidative stress due to decrease in tumour load.

Immunological assessment in patients of leukaemia.

In the present study delayed cutaneous hypersensitivity response (DNCB test) and humoral response (by uantification of immunoglobulins) ware carried out in 20 cases of leukaemias. None of the cases was found to be anergic or immunodeficient. In remission also patients showed the normal response.

Serum vitamin E levels in patients of chronic myeloid leukaemia.

OBJECTIVE: To estimate vitamin E levels in sera of patients of chronic myeloid leukaemia (CML) before and after treatment with busulphan and hydroxyurea and to compare the levels with those in healthy controls. METHODS: The study was carried out in a total of 50 subjects (mean age 34 +/- 8.86 years; 25 were proved cases of CML and 25 were healthy controls. Vitamin E level was measured by spectrofluorometeric method. In patients of CML vitamin E level was estimated twice i.e. once when their total leucocyte count (TLC) was raised (i.e. before treatment) and then after treatment after bringing the TLC near normal. RESULTS: The mean serum vitamin E level in 25 normal healthy controls was 7.19 micrograms/ml and that in 25 patients of CML at presentation (before treatment) was 2.67 micrograms/ml. It increased to 3.61 micrograms/ml after treatment. CONCLUSION: The results show that patients of CML have a significantly lower (p < 0.001) level of serum vitamin E as compared to normal healthy adults and that the level of vitamin E increased significantly (p < 0.001) after treatment even without supplementing vitamin E.

Alpha tocopherol concentration in serum of critically ill patients.

OBJECTIVE: Alpha tocopherol is the biologically and chemically active form of vitamin E and is the most abundant lipid-soluble antioxidant in humans protecting the cell membranes. Serum concentration of the antioxidant alpha tocopherol was measured in critically ill patients in whom the excessive generation of reactive oxygen species could compromise antioxidant defence mechanisms. METHOD: Alpha tocopherol concentration in serum was measured spectrofluorometrically in critically ill patients admitted in intensive care unit and age matched healthy adults, patients with diabetes mellitus (DM) and chronic myeloid leukaemia (CML) served as control. RESULTS: Alpha tocopherol levels were significantly lower in critically ill patients (p < 0.001) as compared to healthy control subjects and those in two other disease groups (DM, CML) in which reactive oxygen species are reported to be increased. Elderly patients and patients who stayed longer than 8 days had lower plasma concentration of vitamin E. CONCLUSION: These findings indicate that antioxidant defence could be considerably compromised in these very sick patients and vitamin E supplementation may be beneficial in increasing their antioxidant reserve.

Lipid peroxidation in leukaemia.

OBJECTIVE: Free radicals have been implicated in the pathogenesis of leukaemias, so the degree of lipid peroxidation was studied as a marker of disease activity in patients of leukaemia. METHODS: Lipid peroxidation product malonyldialdehyde (MDA) was estimated in serum from 30 patients of leukaemia by thio-barbituric acid reaction before and after chemotherapy. There were 10 patients of acute myeloid leukaemia (AML), 5 with acute lymphocytic leukaemia (ALL), 15 with chronic myeloid leukaemia (CML) of which 10 were in chronic stable phase and 5 in blast crisis. Twenty healthy age and sex matched individuals served as control. RESULTS: There was a significant increase in MDA levels in AML and ALL patients and serum MDA levels were higher in the active phase of disease than in remission. We observed a direct correlation between peripheral leucocyte counts and MDA levels. In CML, MDA levels were higher, more so in the patients who were in blast crisis. Patients of CML blast crisis who achieved remission showed a significant decrease in MDA levels as compared to those without remission. CONCLUSION: We observed a significant increase in MDA levels in active phase of acute as well as chronic leukaemia than those in remission. The proposed mechanism for high MDA is that myeloid cells are a major source of superoxide and other oxygen metabolites which lead to lipid peroxidation. MDA estimation in leukaemia can be of help in detecting type of leukaemia, response of therapy, and to predict the chances of relapse.

Effect of treatment on pulmonary functions in chronic severe anaemia.

Pulmonary functions were measured in 15 patients with severe chronic anaemia (haemoglobin level < 5 g/dl). The measurements were repeated after correction of anaemia (Hb > 10 g/dl). Twenty age and sex matched, asymptomatic, non-smoker subjects served as controls. There was 80-100% improvement in various lung functions after correction of anaemia. Effort dependent parameters, viz FVC, ERV, IC, MVV were low in anaemic patients which improved with the rise of haemoglobin. The TLCO, DM, VC, KCO were not significantly influenced during anaemic state. FEV1, PEFR, RV/TLC were essentially normal. We conclude that the observed changes produced in lung functions during anaemic state are fully reversible after its correction.