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Abstract
The ALL is the most common childhood malignancy, accounting for approximately 30% of childhood cancers. Many clinical, biological, genetic, and molecular features have been identified as having prognostic significance in the outcome of patients with ALL. These features are currently used to tailor the intensity of treatment, so that the toxicity of treatment can be minimized, and cure rates can continue to improve.The GST enzyme family is known to catalyze detoxification of carcinogens, therapeutic drugs and products of oxidative stress. GSTM1 genotypes are polymorphic in humans and homozygous deletion of the gene (null GSTM1) is associated with absence of enzyme activity. Thus, GSTM1 null genotype may play a role in increased susceptibility to ALL. Moreover, null GSTM1 may have a prognostic value in detection of outcome of ALL. This study was carried on 40 subjects. They included 30 ALL patients attending Hematology Oncology Unit of Ain Shams University Hospitals. Their mean age was 9.5±4.5 years, with a male to female ratio of 2:1. Ten healthy subjects were studied as control. Their mean age was 8.1±3.0 years, with a male to female ratio of 1:1.Diagnosis of ALL was based on full history, clinical examination, complete blood picture and the presence of >20% blast cells in the BM film together with myelperoxidase negative staining and immuno-phenotyping by FCM. For the detection of GST genotype, RT- PCR analysis was successfully performed on 40 PB (or BM) samples. Fourteen 14/30 patients (46.7%) showed null GSTM1 genotype. As for the controls, none of them showed null GSTM1. Thus, highly significant incidence of null GSTM1 genotype in ALL patients was found in the present work.The patients were furtherly subdivided into two groups; null GSTM1 group and positive GSTM1 group. When a comparative study was done between null GSTM1 and positive GSTM1 groups regarding various prognostic factors, null GSTM1 patients showed a significantly increased frequency of lower TLCs at diagnosis, as 100% of the null GSTM1 patients had TLC <50x 109/L. However, no statistically significant difference was found between null GSTM1 genotype and positive GSTM1 regarding age, sex, Hb level, PLT count, PB and BM blasts at diagnosis, immunopheno-types or any of the clinical findings in the studied ALL patients.To identify the outcome of ALL in the 30 patients, follow up for 7 to 9 months was done. Out of the 30 patients, 24/30 (80%) achieved remission, and 6/30 (20%) exhibited relapse.Patients were furtherly subdivided into two groups; remission and relapse, both of which were compared regarding various prognostic factors. A highly significant relation was found between relapse and higher TLCs (83.3% of relapsed patients had TLC >50x 109/L), higher Hb level (100% of relapsed patients had Hb level >10g/dl), and lower PLT counts at diagnosis (100% of relapsed patients had PLT count <100x 109/L). However, no statistically significant difference was found between remission and relapse groups, regarding age, sex, immunophenotypes or any of the clinical features of the studied ALL patients.Concerning the impact of GSTM1 genotype on the outcome of ALL, 13/14 (92.9%) null GSTM1 patients achieved remission, while 1/14 (7.1%) null GSTM1 patients relapsed. whereas 11/16 (68.8%) patients with positive GSTM1 achieved remission, 5/16 (31.3%) patients with positive GSTM1 relapsed. There was no statistically significant difference between null GSTM1 and positive GSTM1 as regards the outcome of the disease.