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In vitro cellular drug resistance in children with relapsed/refractory
acute lymphoblastic leukemia
E Klumper, R Pieters, AJ Veerman, DR Huismans, AH Loonen, K Hahlen, GJ Kaspers, ER van Wering, R Hartmann and G Henze
Department of Pediatrics, Free University Hospital, Amsterdam, The
Netherlands.
Cellular drug resistance is thought to be an important cause of the poor
prognosis for children with relapsed or refractory acute lymphoblastic
leukemia (ALL), but it is unknown when, to which drugs, and to what extent
resistance is present. We determined in vitro resistance to 13 drugs with
the MTT assay. Compared with 141 children with initial ALL, cells from 137
children with relapsed ALL were significantly more resistant to
glucocorticoids, L-asparaginase, anthracyclines, and thiopurines, but not
to vinca-alkaloids, cytarabine, ifosfamide, and epipodophyllotoxins.
Relapsed ALL cells expressed the highest level of resistance to
glucocorticoids, with a median level 357- and >24-fold more resistant to
prednisolone and dexamethasone, respectively, than initial ALL cells,
whereas the resistance ratios for the other drugs differed from 0.8- to
1.9-fold, intraindividual comparisons between initial and relapsed samples
from 16 children with ALL showed that both de novo and acquired drug
resistance were involved. Specific in vitro drug-resistance profiles were
associated with high-risk relapsed ALL groups. In vitro drug resistance was
also related to the clinical response to chemotherapy in
relapsed/refractory childhood ALL. We conclude that drug resistance may
explain the poor prognosis for children with relapsed/refractory ALL. These
day may be helpful to design alternative treatment regimens for relapsed
childhood ALL.
Volume 86,
Issue 10,
pp. 3861-3868,
11/15/1995
Copyright © 1995 by The American Society of Hematology
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