Isolated Central Nervous System (ICNS) Relapse in Children With Standard Risk (SR) ALL: Results of CCG-1952.
Reviewer: Walter Sall, MD
Last Modified: December 8, 2002
Presenter: Susan Lindemulder Presenter's Affiliation: University of Colorado Health Sciences Center Type of Session: Scientific
The CCG 1952 trial was designed to assess event free survival and ICNS failure in standard risk ALL patients randomized to different chemotherapy regimens.
The ICNS failure rate as well as various related prognostic factors is reported in this abstract.
Materials and Methods
CCG-1952 accrued 2176 eligible patients with SR-ALL by NCI criteria between May 1996 and February 2000.
A 2x2 randomization was used to compare systemic mercaptopurine to thioguanine and intrathecal methotrexate to intrathecal methotrexate, hydrocortisone and cytarabine.
Patients were 56% male, 68% were 2-5 years old, 92.4% had CNS-1 disease. 94.3% were pre-B cell while 5.7% were T-cell histology.
Parameters evaluated for prognostic significance were gender, age, CNS status, WBC phenotype and ethnicity.
82 patients (4%) experienced ICNS relapse at 5 years. The majority occurred by 3 years.
5 year ICNS relapse rate was 5.5% in boys but only 2.8% in girls (p=0.004%).
5 year ICNS relapse rate was 3.6% in CNS-1 disease but 12.0% in CNS-2 disease (p=0.001%).
5 year ICNS relapse was 3% in those age 2-5 years, 10% in those < 2 years and 6% in those > 6 years (p=0.005).
Despite the fact that boys received an additional year of maintenance chemotherapy, their ICNS recurrence rate was significantly higher for unclear reasons.
Boys, CNS-2 patients and patients younger than 2 and older than 6 may benefit from more intensive therapy.
It is possible that the substitution of dexamethasone for prednisone may offset the adverse prognostic factors seen in this study.
This study helps define prognostic factors which can help to identify those ALL patients at highest risk of ICNS relapse following aggressive therapy for SR ALL. Further study of more aggressive CNS prophylaxis in these patients is justified in order to help reduce the risk of CNS recurrence. Basic science research to help determine the etiology of the higher CNS risk in the oldest and youngest patients as well as boys is also warranted.
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