The circadian schedule for childhood acute lymphoblastic leukemia maintenance therapy does not influence event-free survival in the NOPHO ALL92 protocol.

Abstract

BACKGROUND:

The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning.

PROCEDURE:

In the ALL92 MT study we prospectively registered the intake of MTX/6MP. The registration was done when blood samples for erythrocyte MTX/6MP metabolite measurements were collected, and referred to the time of intake in the period since last registration. Nine thousand one hundred ninety-five registrations in total. The administration of MTX/6MP was scored as morning, midday, or evening.

RESULTS:

Of 532 patients, 296 took their medication consistently in the evening, 129 in the evening 50.0-99.9% of the time, and 101 in the evening <50% of the time, six did not have any registrations. The circadian schedule did not differ significantly by age, sex, MTX/6MP doses, and average absolute neutrophil counts. The circadian schedule groups did differ on risk groups (P = 0.003) with fewer HR patients in the 50-99.9% group, and there was a negative correlation between percentage of time on evening schedule and average WBC (Spearman's rho -0.15; P = 0.0004). Average WBC was not associated with relapse on ALL92. In a Cox multivariate model the circadian schedule of MTX/6MP was not of prognostic significance for the risk of relapse, and the 10-year cumulative relapse risk was below 20% in all groups.

CONCLUSION:

An evening schedule may still be recommended based on the previous publications, but in this study morning administration of MTX and 6MP does not seem to impact EFS.

• Authors: Kim K B Clemmensen, Regitse H Christensen, Diana N Shabaneh, Arja Harila-Saari, Mats Heyman, Olafur G Jonsson, Finn Wesenberg, Susanne Rosthøj, Kjeld Schmiegelow, Nordic Society of Pediatric Hematology, Oncology (NOPHO)
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 61 Issue 4 Pg. 653-8 (Apr 2014) ISSN: 1545-5017 [Electronic] United States
• PMID: 24265159 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• Mercaptopurine
• Methotrexate

Topics

• Administration, Oral
• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Child
• Child, Preschool
• Circadian Rhythm
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infant
• Male
• Mercaptopurine (administration & dosage)
• Methotrexate (administration & dosage)
• Neoplasm Recurrence, Local (drug therapy, mortality, pathology)
• Neoplasm Staging
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, mortality, pathology)
• Prognosis
• Prospective Studies
• Survival Rate