In vitro cytotoxicity of mitoxantrone, daunorubicin and doxorubicin in untreated childhood acute leukemia.
Mitoxantrone (MIT) has not been studied as a single agent in children with untreated leukemia. The antileukemic activity of MIT in these patients and its activity in relation to clinical and cell biological features is unknown. We studied the in vitro cytotoxicity of MIT, daunorubicin (DNR) and doxorubicin (DOX) in untreated childhood acute lymphoblastic leukemia (ALL, n = 131) and acute nonlymphoblastic leukemia (ANLL, n = 20) samples, using the MTT assay. There were marked interindividual differences in resistance to all three drugs. A strong, significant cross-resistance was found in ALL between MIT, DNR and DOX. All samples of the T-lineage, a prognostically unfavorable immunophenotype, however, were significantly more resistant to DNR and DOX, but not to MIT, than common or pre-B ALL samples. ALL cells from children with a prognostically unfavorable age at diagnosis, especially those < 2 years, showed a relative resistance to all three drugs compared to the intermediate age-group. This was found within all patients, but also within the common or pre-B ALL cases only. Sex, white blood cell count, or FAB type was not related to in vitro drug resistance. None of the three drugs showed an overall preferential activity in ALL or ANLL. We conclude that the in vitro antileukemic activity of MIT, DNR and DOX is related to certain clinical and cell biological features. There were no major differences between the three drugs in antileukemic activity, except that T-ALL samples were more resistant than common or pre-B ALL samples to DNR and DOX, while MIT was equally active in these two immunophenotypes.
Kaspers
G L
GL
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
Veerman
A J
AJ
Pieters
R
R
van Zantwijk
I
I
Klumper
E
E
Hählen
K
K
de Waal
F C
FC
van Wering
E R
ER
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000494:pharmacology / Q000633:toxicity*; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology / Q000633:toxicity*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004317:Doxorubicin; D008942:Mitoxantrone; D003630:Daunorubicin