Increased in vitro cellular drug resistance is related to poor outcome in high-risk childhood acute lymphoblastic leukaemia
Britt-Marie Frost
Department of Women's and Children's Health, University Children's Hospital,
Search for more papers by this authorPeter Nygren
Department of Oncology, Radiology and Clinical Immunology, University Hospital, Uppsala,
Search for more papers by this authorGöran Gustafsson
Department of Paediatric Oncology, Karolinska Institute, Stockholm,
Search for more papers by this authorErik Forestier
Department of Clinical Sciences, Paediatrics, University of Umeå, Sweden,
Search for more papers by this authorOlafur G. Jonsson
Department of Paediatrics, Landspitali, Reykjavik, Iceland,
Search for more papers by this authorJukka Kanerva
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland,
Search for more papers by this authorRandi Nygaard
Department of Paediatrics, St Olav University Hospital, Trondheim, Norway,
Search for more papers by this authorKjeld Schmiegelow
Paediatric Clinic II, Rigshospitalet, Copenhagen, Denmark, and
Search for more papers by this authorRolf Larsson
Department of Medical Sciences, Section of Pharmacology, University Hospital, Uppsala, Sweden
Search for more papers by this authorGudmar Lönnerholm
Department of Women's and Children's Health, University Children's Hospital,
Search for more papers by this authorOn behalf of the Nordic Society for Paediatric Haematology and Oncology
Search for more papers by this authorBritt-Marie Frost
Department of Women's and Children's Health, University Children's Hospital,
Search for more papers by this authorPeter Nygren
Department of Oncology, Radiology and Clinical Immunology, University Hospital, Uppsala,
Search for more papers by this authorGöran Gustafsson
Department of Paediatric Oncology, Karolinska Institute, Stockholm,
Search for more papers by this authorErik Forestier
Department of Clinical Sciences, Paediatrics, University of Umeå, Sweden,
Search for more papers by this authorOlafur G. Jonsson
Department of Paediatrics, Landspitali, Reykjavik, Iceland,
Search for more papers by this authorJukka Kanerva
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland,
Search for more papers by this authorRandi Nygaard
Department of Paediatrics, St Olav University Hospital, Trondheim, Norway,
Search for more papers by this authorKjeld Schmiegelow
Paediatric Clinic II, Rigshospitalet, Copenhagen, Denmark, and
Search for more papers by this authorRolf Larsson
Department of Medical Sciences, Section of Pharmacology, University Hospital, Uppsala, Sweden
Search for more papers by this authorGudmar Lönnerholm
Department of Women's and Children's Health, University Children's Hospital,
Search for more papers by this authorOn behalf of the Nordic Society for Paediatric Haematology and Oncology
Search for more papers by this authorAbstract
Summary. We determined the in vitro cellular drug resistance in 370 children with newly diagnosed acute lymphoblastic leukaemia (ALL). The resistance to each of 10 drugs was measured by the fluorometric microculture cytotoxicity assay (FMCA) and was related to clinical outcome. The median follow-up time was 41 months. Risk-group stratified analyses indicated that in vitro resistance to dexamethasone, doxorubicin and amsacrine were each significantly related to the probability of disease-free survival. In the high-risk (HR) group, increased in vitro resistance to dexamethasone (P = 0·014), etoposide (P = 0·025) and doxorubicin (P = 0·05) was associated with a worse clinical outcome. Combining the results for these drugs provided a drug resistance score with an independent prognostic significance superior to that of any other factor studied, with a relative risk of relapse in the most resistant group 9·8 times that in the most sensitive group (P = 0·007). The results in the intermediate-risk (IR) and standard-risk (SR) groups were less clear cut. In conclusion, our data indicate that in vitro testing of cellular drug resistance can be used to predict the clinical outcome in HR ALL, while the final evaluation of the results in IR and SR patients must await longer follow-up.
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