title: The rate of in vitro fludarabine-induced peripheral blood and bone marrow cell apoptosis may predict the chemotherapy outcome in patients with chronic lymphocytic leukemia.
abstract: OBJECTIVE
  The problem of drug sensitivity and predicting the outcome of chemotherapy seems to be of great importance in hemato-oncological disorders. There are some factors that can help to predict effects of chemotherapy in chronic lymphocytic leukemia (CLL), such as presence of del17p, del11q, or TP53 gene mutations, which result in resistance to purine analogues and alkylating drugs. Despite the new therapeutic options introduced recently, purine analogues in combination with cyclophosphamide and the monoclonal antibody rituximab is still the gold standard for the first-line treatment of fit patients with CLL. The aim of this study was to assess whether the rate of apoptosis caused by one of purine analogues-fludarabine in cell cultures differs between patients who clinically respond to fludarabine-based chemotherapy and those who do not respond.
  
  
  METHODS
  CLL leukemic cells, obtained from peripheral blood and bone marrow of 23 patients, were cultured in the presence of fludarabine. After 24 h of incubation, the rate of apoptosis, indicated by the expression of active caspase-3, was assessed with flow cytometry and then analyzed regarding clinical response to fludarabine-based regimens.
  
  
  RESULTS
  The percentage of apoptotic cells induced by fludarabine was significantly higher in the group of patients who achieved remission in comparison to the group with no response to purine analogues therapy. Interestingly, we observed that among the patients who did not respond to chemotherapy, the presence of del17p and del11q was detected only once. Other non-responders had no detectable genetic abnormalities.
  
  
  CONCLUSIONS
  Based on these results, it can be presumed that in vitro drug sensitivity test, which is easy to perform, may predict the outcome of fludarabine-based chemotherapy in CLL patients.
authors.affiliation: Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Staszica 11, 20-081, Lublin, Poland, monika.podhorecka@onet.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Podhorecka
authors.forename: Piotr
authors.initials: P
authors.lastname: Klimek
authors.forename: Sylwia
authors.initials: S
authors.lastname: Chocholska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymczyk
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Macheta
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kowal
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Marek
authors.initials: M
authors.lastname: Hus
mesh_terms: D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018956:CD5 Antigens / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D012074:Remission Induction; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018941:Antigens, CD19; D000970:Antineoplastic Agents; D018956:CD5 Antigens; D053148:Caspase 3; D014740:Vidarabine; C024352:fludarabine