Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia

R Pieters, DR Huismans, AH Loonen, AJP Veerman… - The Lancet, 1991 - Elsevier
R Pieters, DR Huismans, AH Loonen, AJP Veerman, K Hahlen, ER Wering
The Lancet, 1991Elsevier
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 …
Abstract
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.
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