Introduction: Despite steady improvement in therapy of lymphoblastic leukemia, 20-25% of patients still experience a relapse. CNS relapse in children with ALL became clinically apparent as bone marrow remissions became more durable. Although the frequency of isolated meningeal relapse is currently only 5% or less in most studies, it remains a significant problem with regard to definition, treatment, or outcome. The main factors determining the success rate for patients with CNS relapse include whether the relapse occurred more than or less than 18 months (83% and 46% EFS respectively) from the initial diagnosis and whether the patient received CNS directed irradiation during the initial treatment regimen.Objective: The aim of the current study is to assess the implemented rationale for CNS prophylaxis and CNS treatment in newly diagnosed pediatric patients with acute lymphoblastic leukemia (ALL) in the period between January 2005 and June 2006.Patients and methods: During this period, 151 cases presented with ALL. In attempt to identify the factors associated with treatment failure, the clinico-pathological characteristics of patients with maintained complete remission will be compared with those of patients showed relapse. Data of patients who experienced CNS relapse during the period of the study, whether isolated or combined with systemic relapse, will be analyzed to identify the risk factors that may be associated with CNS relapse.Results: The study included 151 patients with ALL, 83 were males and 68 were females. CNS disease at presentation was reported in 8 patients (5.3%). According to age, initial total leucocytic count, CNS status & immunophenotype (as T-cell ALL is considered high risk), patients included in the current study were stratified into low risk; 75 patients (49.6%), and high risk; 76 patients (50.4%). The induction mortality rate was 2.6%. Complete remission by the end of induction was present in 99.4%. Out of these 151 patients, 12 patients were excluded (6 of them because of early deaths, and the other 6 patients lost follow up). Out of the 139 evaluable patients, 24 patients had relapse (Relapse Rate 17.3%). CNS relapse was observed in 16 patients (11.5%). Statistical difference was found in patients with initial high TLC, T-cell ALL, CNS disease at presentation, high risk group patients, and patients who did not receive different modalities of CNS prophylaxis and treatment. Conclusion: Egyptian patients are usually presented with poor prognostic factors. This can partly be explained by biologically more aggressive tumor and/or late diagnosis of disease in Egypt. The only factors that independently affect CNS relapse were whether the case is T-cell vs progenitor B-cell and having CNS disease at presentation vs not.