Immunophenotypic cell lineage and in vitro cellular drug resistance in childhood relapsed acute lymphoblastic leukaemia.
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.
Kaspers
Gertjan J L
GJ
Department of Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands. gjl.kaspers@vumc.nl
Wijnands
Jelle J M
JJ
Hartmann
Reinhard
R
Huismans
Loekie
L
Loonen
Anne H
AH
Stackelberg
Arend
A
Henze
Guenter
G
Pieters
Robrecht
R
Hählen
Karel
K
Van Wering
Elisabeth R
ER
Veerman
Anjo J P
AJ
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
D000970:Antineoplastic Agents