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.

Acute lymphoblastic leukaemia, B-cell precursor ALL, Childhood, Drug resistance, Immunophenotype, MTT assay, Relapse, T-cell ALL, Tailored therapy, Thiopurines,
European Journal of Cancer
Department of Pediatrics

Kaspers, G.J.L, Wijnands, J.J.M, Hartmann, R, Huismans, L, Loonen, A.H, von Stackelberg, A, … Veerman, A.J.P. (2005). Immunophenotypic cell lineage and in vitro cellular drug resistance in childhood relapsed acute lymphoblastic leukaemia. European Journal of Cancer, 41(9), 1300–1303. doi:10.1016/j.ejca.2005.02.026