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In vitro cellular drug resistance adds prognostic information to other known risk-factors in childhood acute lymphoblastic leukemia |
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| Authors: | Lönnerholm Gudmar Thörn Ingrid Sundström Christer Frost Britt-Marie Flaegstad Trond Heyman Mats Jonsson Olafur Gisli Harila-Saari Arja Madsen Hans O Porwit Anna Schmiegelow Kjeld Söderhäll Stefan Wesenberg Finn Vettenranta Kim Larsson Rolf Forestier Erik |
| Affiliation: | a Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden b Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden c Departmnt of Pediatrics, University and University Hospital, Tromsoe, Norway d Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden e Department of Pediatrics, Landspitalinn, Reykjavik, Iceland f Department of Pediatrics and Adolescence, Oulu University Hospital, Oulu, Finland g Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark h Department of Pathology, Karolinska University Hospital, Stockholm, Sweden i Pediatric Clinic II, Rigshospitalet, Copenhagen, Denmark j Department of Pediatrics, National Hospital, Oslo, Norway k Department of Pediatrics, University of Tampere, Finland l Department of Medical Sciences, Section of Pharmacology, University Hospital, Uppsala, Sweden m Department of Clinical Sciences, Paediatrics, University of Umeå, Sweden |
| Abstract: | Leukemic cells from 230 children with newly diagnosed B-cell precursor ALL were tested for in vitro drug resistance to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. During follow-up, 24 relapses occurred in the 159 children with MRD <0.1% day 29. The risk of any relapse was correlated to vincristine and doxorubicin resistance, with a relative risk of 3.7 (95% CI 1.3-10.5; p = 0.016) for patients resistant to both drugs. There was a significant correlation also for the subgroup with extra-medullary relapses. Our findings indicate that analysis of drug resistance can add prognostic information to other known risk-factors including MRD. |
| Keywords: | acute lymphoblastic leukemia childhood in vitro drug resistance MRD prognostic factors |
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