title: Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia.
abstract: To improve the efficacy of therapeutic options in chronic lymphocytic leukemia (CLL) an in vitro system to determine the response of mononuclear blood cells from blood of patients was elaborated. The study combines four approaches, i.e., cell viability, apoptosis rate, differential scanning calorimetry (DSC), and immunoblotting to develop personalized therapy protocols based on the cell sensitivity to drug exposure of individual CLL patients. The complementary analyses were performed on 28 peripheral blood samples from previously untreated CLL patients before therapy. The induction and progress of apoptosis in CLL cells exposed in vitro to purine analogs combined with mafosfamide, i.e., cladribine + mafosfamide (CM) and fludarabine + mafosfamide (FM) were assessed using the above approaches. The changes in thermal profiles (decrease/loss of transition at 95±5˚C) coincided with an accumulation of apoptotic cells, a decrease in the number of viable cells, and differences in the expression of the apoptosis‑related protein PARP‑1. No significant changes were observed in the thermal profiles of nuclei isolated from CLL cells resistant to the treatment. The complementary assays revealed a strong relationship between both the in vitro sensitivity of leukemia cells to drugs and the clinical response of the patients, determined usually after the sixth course of treatment (after ~6 months of therapy). As a summary of studies followed by complementary tests, our findings demonstrate the value of in vitro exposure of CLL cell samples to drugs intended to treat CLL patients, before their administration in order to recommend the most suitable and effective therapy for individual patients.
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rogalińska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Jerzy Z
authors.initials: JZ
authors.lastname: Błoński
authors.affiliation: Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Góralski
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wawrzyniak
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Hartman
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Rogalska
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Robak
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Koceva-Chyła
authors.affiliation: Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Piekarski
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors.forename: Zofia M
authors.initials: ZM
authors.lastname: Kiliańska
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017338:Cladribine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D017338:Cladribine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine