Elsevier

The Lancet

Volume 338, Issue 8764, 17 August 1991, Pages 399-403
The Lancet

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

https://doi.org/10.1016/0140-6736(91)91029-TGet rights and content

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.

References (31)

  • Jm Sargent et al.

    Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia

    Br J Cancer

    (1989)
  • Pr Twentyman et al.

    Chemosensitivity testing of fresh leukaemia cells using the MTT colorimetric assay

    Br J Haematol

    (1989)
  • R. Pieters et al.

    Comparison of a rapid automated tetrazolium based (MTT-)assay with a dye exclusion assay for chemosensitivity testing in childhood leukemia

    Br J Cancer

    (1989)
  • T. Hongo et al.

    An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia

    Cancer

    (1990)
  • R. Pieters

    Drug resistance in childhood leukemia

    (1991)
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