TY - JOUR

T1 - 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

AU - Schmiegelow, Kjeld

AU - Heyman, Mats

AU - Kristinsson, Jon

AU - Mogensen, Ulla B

AU - Rosthøj, Susanne

AU - Vettenranta, Kim

AU - Wesenberg, Finn

AU - Saarinen-Pihkala, Ulla

AU - Nordic Society of Paediatric Haematology and Oncology (NOPHO)

N1 - Keywords: 6-Mercaptopurine; Administration, Oral; Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Female; Humans; Infant; Male; Methotrexate; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Risk Factors; Survival Analysis; Treatment Outcome; Vincristine

PY - 2009

Y1 - 2009

N2 - 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 > or =50 x 10/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 > or =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.

AB - 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 > or =50 x 10/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 > or =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.

U2 - 10.1097/MPH.0b013e3181a6e171

DO - 10.1097/MPH.0b013e3181a6e171

M3 - Journal article

C2 - 19648786

VL - 31

SP - 385

EP - 392

JO - Journal of Pediatric Hematology/Oncology

JF - Journal of Pediatric Hematology/Oncology

SN - 1077-4114

IS - 6

ER -