Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: a single-institution experience.
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.


CONCLUSIONS
Outcome in children with ALL has improved because of intensification of treatment protocols and better supportive care.
Al-Nasser
Abdallah
A
Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. alnasser@kfshrc.edu.sa
El-Solh
Hassan
H
De Vol
Edward
E
El-Hassan
Ibrahim
I
Alzahrani
Ali
A
Al-Sudairy
Reem
R
Al-Mahr
Mohammed
M
Al-Musa
Abdulrahman
A
Al-Jefri
Abdulla
A
Saleh
Mahasen
M
Rifai
Samira
S
Belgaumi
Asim
A
Osman
Layla
L
Ashraf
Khairy
K
Salim
Mohammed
M
Silo
Ameurfina
A
Roberts
George
G
D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D012529:Saudi Arabia; D016019:Survival Analysis; D016896:Treatment Outcome