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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

Schmiegelow, Kjeld MD, PhD* †; Heyman, Mats MD, PhD; Kristinsson, Jon MD§; Mogensen, Ulla B. MSc; Rosthøj, Susanne MSc; Vettenranta, Kim MD, PhD; Wesenberg, Finn MD, PhD; Saarinen-Pihkala, Ulla MD, PhD, and On Behalf of the Nordic Society of Paediatric Haematology and Oncology (NOPHO)

Journal of Pediatric Hematology/Oncology: June 2009 - Volume 31 - Issue 6 - p 385-392
doi: 10.1097/MPH.0b013e3181a6e171
Original Articles

The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance therapy with a multidrug cyclic LSA2L2 regimen. 135 children with B-lineage ALL and a white blood count ≥50×109/L and 98 children with T-lineage ALL were included. Of the 234 patients, the 135 patients who received MTX/6MP maintenance therapy had a lower relapse risk than the 98 patients who received LSA2L2 maintenance therapy, which was the case for both B-lineage (27%±5% vs. 45%±9%; P=0.02) and T-lineage ALL (8%±5% vs. 21%±5%; P=0.12). In multivariate Cox regression analysis stratified for immune phenotype, a higher white blood count (P=0.01) and administration of LSA2L2 maintenance therapy (P=0.04) were both related to an increased risk of an event (overall P value of the Cox model: 0.003), whereas neither sex, age at diagnosis, administration of central nervous system irradiation, nor presence of a day 15 bone marrow with ≥25% versus <25% lymphoblasts were of statistical significance. These results indicate that oral MTX/6MP maintenance therapy administered after the first year of remission can improve the cure rates of children with T-lineage or with higher risk B-lineage ALL.

*Institute of Gynecology, Obstetrics, and Pediatrics, the Faculty of Medicine

Department of Biostatistics, University of Copenhagen

Departments of Pediatrics, University Hospitals, Rigshospitalet Copenhagen, Denmark

Astrid Lindgrens Barnsjukhus, Stockholm, Sweden

§Landspitalin Reykjavik, Iceland

Helsinki, Finland

Rikshospitalet, Oslo, Norway

This study has received financial support from The Childhood Cancer Foundation, Denmark; The University Hospital Rigshospitalet; and The Lundbeck Foundation (grant no.: 38/99), The NovoNordisk Foundation; Home Secretary Research Grant for Individualised Therapy; The Danish Research Council for Health and Disease. Kjeld Schmiegelow holds the Childhood Cancer Foundation Research Professorship in Pediatric Oncology.

Reprints: Kjeld Schmiegelow, MD, The Pediatric Clinics, Juliane Marie Center 5704, University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark (e-mail:

Received for publication December 16, 2008; accepted March 15, 2009

© 2009 Lippincott Williams & Wilkins, Inc.