title: Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial.
abstract: Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pluta
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Wrzesien-Kus
authors.affiliation: Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Bozena
authors.initials: B
authors.lastname: Katarzyna Budziszewska
authors.affiliation: Department of Clinical Hematology, Military Medical Academy, Warsaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Sulek
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wawrzyniak
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Czemerska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zwolinska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Golos
authors.affiliation: Department of Oncology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Holowiecka-Goral
authors.affiliation: University Department of Hematology and BMT, Silesian Medical University, Katowice, Poland.
authors.forename: Slawomira
authors.initials: S
authors.lastname: Kyrcz-Krzemien
authors.affiliation: Department of Hematology, Bialystok Medical Academy, Bialystok, Poland.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Piszcz
authors.affiliation: Department of Hematology, Bialystok Medical Academy, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland and Lower Silesian Center for Cellular Transplantation & National Bone Marrow Donor Registry, Wrocław, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Mordak-Domagala
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland and Lower Silesian Center for Cellular Transplantation & National Bone Marrow Donor Registry, Wrocław, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
authors.affiliation: Hematology Department, Rydygier Memorial Hospital, Krakow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Razny
authors.affiliation: Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Madry
authors.affiliation: Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Wiktor-Jedrzejczak
authors.affiliation: Department of Cancer Prevention, Faculty of Public Health, Silesian Medical University, Katowice, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grosicki
authors.affiliation: Department of Physiology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Butrym
authors.affiliation: Department of Hematology and Proliferative Diseases, Wroclaw Medical Academy, Wroclaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
authors.affiliation: Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.affiliation: Department of Bone Marrow Transplantation, Comprehensive Cancer Center, M. Sklodowska-Curie Memorial Institute, Gliwice, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.affiliation: Department of Bone Marrow Transplantation, Comprehensive Cancer Center, M. Sklodowska-Curie Memorial Institute, Gliwice, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.affiliation: Hammersmith Hospital, Centre for Haematology, Imperial College London, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agnieszka
authors.identifier: http://orcid.org/0000-0001-7909-457X
authors.initials: A
authors.lastname: Wierzbowska
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017338:Cladribine / Q000008:administration & dosage* / Q000494:pharmacology; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011044:Poland; D012074:Remission Induction
chemical_list: D003561:Cytarabine; D017338:Cladribine; D003630:Daunorubicin