The study was designed to improve outcome in patients with childhood acute lymphoblastic leukemia (ALL) by using a reduced treatment regimen. Methods: The study was conducted at Kasr El-Einy Center for Oncology (NEMROCK)- Faculty of Medicine, Cairo University. The study included 43 children complaining of acute lymphoblastic leukemia age ranging from 10 months-15 years and a mean of 6.5 years. Male to female ratio was 1: 8. Patients were stratified into standard risk group (SRG), a medium risk group (MRG), both defined by adequate early treatment response; and a high risk group (HRG), defined by inadequate response to the cytoreductive prednisone prephase, induction failure, or Philadelphia chromosome positive ALL. Four treatment modifications were evaluated: dose intensification in induction by a more rapid drug sequence; administration of L-asparginase during consolidation therapy in the MRG (randomized); enforced consolidation by rotational elements in the HRG; reduction of anthracycline and use of only 12 Gy preventive cranial radiotherapy in the MRG and HRG, with the aim of avoiding toxicity. Results: The patients were stratified into SRG (2 cases, 6%), MRG (16 cases, 37%) and HRG (25 cases, 58%). Cytogenetic profile is an independent prognostic factor with increasing importance nowadays having a prognostic significance. The translocation t(9;22) was found in 3 cases 7%, t(1; 19) in 4 cases, 9% and the t(4;11) in 5 cases 12%. Patient stratification, early response to prednisone as well as cytogenetic studies improve treatment outcome in childhood ALL with decreasing toxicity.