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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: a
Abdallah Al-Nasser1, Hassan El-Solh, Edward De Vol
1Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. alnasser@kfshrc.edu.sa
Insights
Intensified treatment and improved supportive care significantly enhanced outcomes for children with acute lymphoblastic leukemia (ALL). This led to a dramatic increase in event-free survival rates over an 18-year period.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Research
Background:
- Acute lymphoblastic leukemia (ALL) is a significant childhood cancer.
- Optimizing treatment for pediatric ALL requires understanding patient characteristics and therapeutic outcomes.
- There is a need for data on the least toxic and most effective ALL therapies for children.
Purpose of the Study:
- To review treatment experience for pediatric ALL over 18 years.
- To analyze patient characteristics and outcomes in ALL treatment.
- To identify factors influencing treatment effectiveness and toxicity in children with ALL.
Main Methods:
- Retrospective review of 509 children with ALL treated between 1981 and 1998.
- Comparison of outcomes between local protocols (Era 1: 1981-1992) and international protocols (Era 2: 1993-1998).
- Analysis of clinical presentation, laboratory findings, risk factors, stratification, therapy, and patient outcomes.
Main Results:
- The end-of-induction remission rate improved from 90% to 95% (P=.049).
- Five-year event-free survival (EFS) significantly improved from 30.6% to 64.2% (P<.001).
- Improvements were achieved without a significant increase in morbidity or mortality, attributed to enhanced systemic therapy and supportive care.
Conclusions:
- Intensification of treatment protocols has improved outcomes in pediatric ALL.
- Enhanced supportive care plays a crucial role in improving survival rates.
- Key prognostic factors include therapy intensity, risk category, and central nervous system disease at diagnosis.
Background And Objective:
Because of the need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and King Fahad National Center for Children's Cancer and Research (KFNCCC&R) over a period of 18 years with a focus on patient characteristics and outcome.
Methods:
During the period of 1981 to 1998, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90), and subsequently, Children's Cancer Group (CCG) protocols, and these were grouped as Era 1 (1981-1992) and Era 2 (1993-1998).
Results:
Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotrexate (MTX) 1 g/m(2) and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 and cyclophosphamide. International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs during the post-remission period. The end-of-induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=.049). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P<.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important independent prognostic factors were intensity of therapy, poor risk category assignment and CNS disease at diagnosis.
Conclusion:
Outcome in children with ALL has improved because of intensification of treatment protocols and better supportive care.
