title: Lack of cross-resistance between prednisolone and methotrexate in childhood acute lymphoblastic leukemia? A preliminary analysis.
abstract: We studied the cross-resistance between prednisolone (PRD) and methotrexate (MTX) in children with newly diagnosed acute lymphoblastic leukemia (ALL). This was done because of a previous observation that such patients could show a good clinical response to systemic PRD monotherapy plus intrathecal MTX, despite in vitro PRD resistant ALL cells (as determined with the MTT assay). This suggests an antileukemic effect of MTX, and thus the lack of cross-resistance between PRD and MTX. A systemic antileukemic effect of intrathecally administered MTX has been reported in the literature. Clinical good responders with PRD resistant ALL cells (n = 15) did not show unfavorable MTX-polyglutamylation nor unfavorable low inhibition of thymidylate synthase by MTX, as compared to a heterogeneous group of newly diagnosed ALL children (n = 47). In addition, we did not find a significant correlation between these two parameters and in vitro PRD resistance within the clinical good responders with PRD resistant ALL cells. In conclusion, we did not find a significant cross-resistance between PRD and MTX in vitro. It therefore may be that the good clinical response to systemic PRD plus intrathecal MTX in patients with in vitro PRD resistant ALL cells was caused by a systemic antileukemic activity of the intrathecally administered MTX.
authors.affiliation: Department of Pediatric Hematology/Oncology, University Hospital Vrije Universiteit, Amsterdam.
authors.forename: I R
authors.initials: IR
authors.lastname: Hegge
authors.forename: G J
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: M G
authors.initials: MG
authors.lastname: Rots
authors.forename: G
authors.initials: G
authors.lastname: Jansen
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: A J
authors.initials: AJ
authors.lastname: Veerman
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002648:Child; D015925:Cryopreservation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011239:Prednisolone / Q000627:therapeutic use*; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D011239:Prednisolone; D008727:Methotrexate