The circadian schedule for childhood acute lymphoblastic leukemia maintenance therapy does not influence event-free survival in the NOPHO ALL92 protocol.
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AuthorsClemmensen, Kim K B
Christensen, Regitse H
Shabaneh, Diana N
Jonsson, Olafur G
MetadataShow full item record
CitationPediatr Blood Cancer 2014, 61 (4):653-8
AbstractThe 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.
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.
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.
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.
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RightsArchived with thanks to Pediatric blood & cancer
- Impact of morning versus evening schedule for oral methotrexate and 6-mercaptopurine on relapse risk for children with acute lymphoblastic leukemia. Nordic Society for Pediatric Hematology and Oncology (NOPHO).
- Authors: Schmiegelow K, Glomstein A, Kristinsson J, Salmi T, Schrøder H, Björk O
- Issue date: 1997 Mar-Apr
- Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia.
- Authors: Relling MV, Hancock ML, Boyett JM, Pui CH, Evans WE
- Issue date: 1999 May 1
- Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study.
- Authors: Schmiegelow K, Heyman M, Kristinsson J, Mogensen UB, Rosthøj S, Vettenranta K, Wesenberg F, Saarinen-Pihkala U, Nordic Society of Paediatric Haematology and Oncology (NOPHO).
- Issue date: 2009 Jun
- Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia: influence on cure rates and risk of second cancer.
- Authors: Levinsen M, Rotevatn EØ, Rosthøj S, Nersting J, Abrahamsson J, Appell ML, Bergan S, Bechensteen AG, Harila-Saari A, Heyman M, Jonsson OG, Maxild JB, Niemi M, Söderhäll S, Schmiegelow K, Nordic Society of Paediatric Haematology, Oncology.
- Issue date: 2014 May
- Intravenous 6-mercaptopurine decreases salvage after relapse in childhood acute lymphoblastic leukemia: a report from the Children's Cancer Group study CCG 1922.
- Authors: Tolar J, Bostrom BC, La MK, Sather HN
- Issue date: 2005 Jul