TY - JOUR
T1 - Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia
AU - Pieters, R.
AU - Huismans, D. R.
AU - Loonen, A. H.
AU - Veerman, A. J.P.
AU - Hahlen, K.
AU - van der Does-van den Berg, A.
AU - Wering, E. R.
N1 - Funding Information:
This study was supported by the Dutch Cancer Society (IKA 87-17). We thank the Dutch Childhood Leukemia Study Group for clinical data: board members of the Group are W. A. Kamps, K. Hiihien, F. A. E. Nabben, J. A. Rammeloo, G. A. M. de Vaan, P. J. van Dijken, A. J. P. Veerman, R. S. Weening, E. Th. van ’t Veer-Korthof, A. Postma, I. Risseeuw-Appel, J. P. M. Bokkerink, M. V. A. Bruin, F. C. de Waal, E. F. van Leeuwen, M. van Weel-Sipman.
PY - 1991/8/17
Y1 - 1991/8/17
N2 - The clinical relevance of cellular drug resistance in children with acute lymphoblastic leukaemia (ALL) is unknown. The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT assay was used to assess sensitivity to prednisolone, vincristine, colaspase (asparaginase), daunorubicin, and thioguanine (instead of mercaptopurine which is unstable in vitro). For vincristine and colaspase there was no difference in outcome (probability of continuous complete remission) between sensitive and resistant patients. However, the probability of continuous complete remission was significantly lower in patients with resistant cells than in those with sensitive cells for thioguanine (p<0·01), daunorubicin (p<0·02), and prednisolone (p<0·05). For prednisolone there was a significant worsening of the prognosis (p<0·05) from the extremely sensitive patients through an intermediate group to the most resistant group. The prognostic significance of cellular drug resistance was independent of white-blood-cell count, age, sex, and hepatosplenomegaly. Leukaemic cells from boys were more resistant to thioguanine than those from girls. Thus, the short-term highly efficient MTT assay can help to predict long-term response to chemotherapy in childhood ALL.
AB - The clinical relevance of cellular drug resistance in children with acute lymphoblastic leukaemia (ALL) is unknown. The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT assay was used to assess sensitivity to prednisolone, vincristine, colaspase (asparaginase), daunorubicin, and thioguanine (instead of mercaptopurine which is unstable in vitro). For vincristine and colaspase there was no difference in outcome (probability of continuous complete remission) between sensitive and resistant patients. However, the probability of continuous complete remission was significantly lower in patients with resistant cells than in those with sensitive cells for thioguanine (p<0·01), daunorubicin (p<0·02), and prednisolone (p<0·05). For prednisolone there was a significant worsening of the prognosis (p<0·05) from the extremely sensitive patients through an intermediate group to the most resistant group. The prognostic significance of cellular drug resistance was independent of white-blood-cell count, age, sex, and hepatosplenomegaly. Leukaemic cells from boys were more resistant to thioguanine than those from girls. Thus, the short-term highly efficient MTT assay can help to predict long-term response to chemotherapy in childhood ALL.
UR - http://www.scopus.com/inward/record.url?scp=0025870820&partnerID=8YFLogxK
U2 - 10.1016/0140-6736(91)91029-T
DO - 10.1016/0140-6736(91)91029-T
M3 - Article
C2 - 1678081
AN - SCOPUS:0025870820
SN - 0140-6736
VL - 338
SP - 399
EP - 403
JO - Lancet
JF - Lancet
IS - 8764
ER -