title: Immunophenotypic cell lineage and in vitro cellular drug resistance in childhood relapsed acute lymphoblastic leukaemia.
abstract: At relapse, T-cell acute lymphoblastic leukaemia (ALL) has a worse patient outcome than B-cell precursor (BCP-) ALL. To investigate this further, we compared in vitro cellular drug resistance profiles of T-cell and BCP-ALL samples obtained at relapse. We investigated 237 paediatric relapsed ALL cases, including 151 samples taken at first relapse, of which 30 were T-cell ALL. In vitro drug resistance was measured using the 4-day methyl-thiazol-tetrazolium (MTT) assay and cellular immunophenotype was determined at central reference laboratories. Similar results were found for first relapsed ALL samples and for the total group: T-cell ALL samples were more resistant to 4-HOO-ifosfamide (1.4-fold, P = 0.019) and cisplatin (3.7-fold, P = 0.005). The samples were more sensitive to thiopurines such as mercaptopurine (2.1-fold, P = 0.007) and thioguanine (1.7-fold, P = 0.003). Resistance/sensitivity to 16 other drugs did not differ significantly. These results do not explain the relatively poor prognosis of T-cell ALL at relapse, but do suggest that the more intensive use of thiopurines in relapsed T-cell ALL may be beneficial.
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands. gjl.kaspers@vumc.nl
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Jelle J M
authors.initials: JJ
authors.lastname: Wijnands
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hartmann
authors.forename: Loekie
authors.initials: L
authors.lastname: Huismans
authors.forename: Anne H
authors.initials: AH
authors.lastname: Loonen
authors.forename: Arend
authors.initials: A
authors.lastname: Stackelberg
authors.forename: Guenter
authors.initials: G
authors.lastname: Henze
authors.forename: Robrecht
authors.initials: R
authors.lastname: Pieters
authors.forename: Karel
authors.initials: K
authors.lastname: Hählen
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Van Wering
authors.forename: Anjo J P
authors.initials: AJ
authors.lastname: Veerman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor / Q000276:immunology; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000276:immunology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016130:Immunophenotyping; D007928:Lethal Dose 50; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology; D011379:Prognosis; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents