title: Drug-resistance Profile in Multiple-relapsed Childhood Acute Lymphoblastic Leukemia.
abstract: OBJECTIVE
  To analyze the drug-resistance profile at first and subsequent relapse in children with acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  A total of 154 pediatric ALL samples were tested for ex vivo chemosensitivity for up to 19 drugs. Their combined drug resistance profile (PVA score) was analyzed.
  
  
  RESULTS
  The median relative resistance scores between patients with multiple relapse and those with first relapse considering all drugs was 2.0. The median PVA score at subsequent relapses was 8 vs. 6 at first relapse (p=0.004). Samples from multiple-relapsed ALL were more drug resistant to: prednisolone (>1.9-fold), dexamethasone (>1.5-fold), vincristine (3.1-fold), L-asparaginase (5-fold), mitoxantrone (2.4-fold), cytarabine (4.3-fold), mercaptopurine (2.2-fold), thioguanine (4.8-fold), etoposide (2.6-fold) and melphalan (2.7-fold). Lymphoblasts at multiple relapse were comparably resistant to: daunorubicin, doxorubicin, cyclophosphamide, ifosfamide, busulfan, treosulfan, fludarabine, clofarabine and bortezomib.
  
  
  CONCLUSIONS
  In comparison to first relapse, subsequent relapsed childhood ALL is more ex vivo-resistant to most tested drugs.
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pogorzala
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kubicka
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Rafinska
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland jstyczynski@cm.umk.pl.
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents
keywords: Ex vivo drug resistance; acute lymphoblastic leukemia; children; individualized tumor response testing; minimal residual disease; relapse