TY - JOUR
T1 - In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia
AU - Klumper, Edwin
AU - Pieters, Rob
AU - Veerman, Anjo J.P.
AU - Huismans, Dieuwke R.
AU - Loonen, Annemarie H.
AU - Hählen, Karel
AU - Kaspers, Gertjan J.L.
AU - Van Wering, Elisabeth R.
AU - Hartmann, Reinhard
AU - Henze, Günter
PY - 1995/11/15
Y1 - 1995/11/15
N2 - 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 data may be helpful to design alternative treatment regimens for relapsed childhood ALL.
AB - 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 data may be helpful to design alternative treatment regimens for relapsed childhood ALL.
UR - http://www.scopus.com/inward/record.url?scp=0028803598&partnerID=8YFLogxK
U2 - https://doi.org/10.1182/blood.v86.10.3861.bloodjournal86103861
DO - https://doi.org/10.1182/blood.v86.10.3861.bloodjournal86103861
M3 - Article
C2 - 7579354
SN - 0006-4971
VL - 86
SP - 3861
EP - 3868
JO - Blood
JF - Blood
IS - 10
ER -