Available online at www.sciencedirect.com Leukemia Research 33 (2009) 46–53 In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual disease at end of induction therapy in childhood acute lymphoblastic leukemia Gudmar Lönnerholm a,∗ , Ingrid Thörn b , Christer Sundström b , Britt-Marie Frost a , Jonas Abrahamsson c , Mikael Behrendtz d , Jesper Heldrup e , Stefan Jacobsson f , AiHong Li g , Tor Olofsson h , Anna Porwit i , Stefan Söderhäll j , Rolf Larsson k , Erik Forestier l a Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden b Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden c Qween Silvias Children’s Hospital, Gothenburg, Sweden d Department of Pediatrics, University Hospital, Linköping, Sweden e Department of Pediatrics, Lund University Hospital, Lund, Sweden f Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden g Department of Biosciences, Clinical Genetics, University of Umeå, Sweden h Division of Hematology & Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden i Department of Pathology, Karolinska University Hospital, Stockholm, Sweden j Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden k Department of Medical Sciences, Section of Pharmacology, University Hospital, Uppsala, Sweden l Department of Clinical Sciences, Paediatrics, University of Umeå, Sweden Received 29 February 2008; received in revised form 3 June 2008; accepted 7 June 2008 Available online 17 July 2008 Abstract Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. There was a significant correlation between MRD day 29 and in vitro sensitivity to prednisolone (p < 0.001) and doxorubicin (p = 0.017), drugs administered during induction therapy. In patients with t(12;21) (n = 20), in vitro sensitivity to doxorubicin was an independent factor for MRD <0.1% (p = 0.031; R 2 = 0.66). Thus, data show that in vitro drug sensitivity at diagnosis is correlated to cell kill during induction therapy as measured by MRD day 29. © 2008 Elsevier Ltd. All rights reserved. Keywords: Acute lymphoblastic leukemia; Childhood; In vitro drug resistance; MRD; t(12 ;21); Prednisolone; Doxorubicin 1. Introduction Minimal residual disease (MRD) has evolved as an independent prognostic parameter in childhood acute lym- ∗ Corresponding author at: Department of Women’s and Children’s Health, University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel.: +46 18 6115896; fax: +46 18 6115853. E-mail address: gudmar.lonnerholm@kbh.uu.se (G. Lönnerholm). phoblastic leukemia (ALL) and is currently used in several clinical trials for treatment stratification [1–5]. In vitro mea- surement of drug resistance in leukemic cells obtained at diagnosis has also shown promise in the prediction of clin- ical outcome in selected groups of patients [6–9], but only two small retrospective studies have investigated the rela- tionship between in vitro drug resistance and MRD. In both studies a weak correlation was found between resistance to prednisolone and MRD during and after induction therapy 0145-2126/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2008.06.012