title: Fludarabine/intermediate-dose cytarabine with or without allogeneic hematopoietic stem cell transplantation in poor-risk leukemia: a single center experience.
abstract: Disease recurrence has been and remains the leading cause of treatment failure in patients with high-risk leukemia. We retrospectively analyzed outcome in 61 patients with high-risk leukemia receiving a combination of fludarabine and intermediate-dose cytarabine as induction (n = 11) or salvage therapy (n = 35). Thirty-six patients having a suitable stem cell donor proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Ten patients received fludarabine-based salvage therapy without consecutive allogeneic transplantation and 15 patients received fludarabine/intermediate-dose cytarabine because of disease relapse following allogeneic stem cell transplantation. In patients without prior allogeneic HSCT (n = 46) the complete remission rate (CR) was 41% with a CR rate of 46 and 14% in patients with acute myeloid leukemia (AML) and with acute lymphoblastic leukemia (ALL), respectively. Overall survival for patients achieving a CR was 41 versus 0% for patients not achieving CR (P < 0.0001). The best outcome was observed in patients receiving an allogeneic HSCT in CR following fludarabine/ intermediate-dose cytarabine (47 vs. 0% for patients not in CR at the time of allografting, P = 0.01). All 10 patients receiving fludarabine/intermediate-dose cytarabine without subsequent allogeneic HSCT died within 3 years either of disease relapse/progression or infection. Only 1/15 (7%) patients receiving fludarabine/intermediate-dose cytarabine because of relapse following allogeneic HSCT became a long-term survivor. By multivariate analysis achieving CR, receiving an allogeneic HSCT, and being in first relapse or untreated were the only parameters that significantly determine the outcome. Although preliminary only high-risk AML patients having a stem cell donor are candidates for fludarabine/intermediate-dose cytarabine and only those achieving a CR should be referred to subsequent allogeneic HSCT. All other patients with high-risk leukemia are candidates for experimental therapies within controlled trials.
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria. jutta.auberger@i-med.ac.at.
authors.forename: Jutta
authors.initials: J
authors.lastname: Auberger
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Clausen
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Willenbacher
authors.affiliation: Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University, Innsbruck, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Erdel
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Gunsilius
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Petzer
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Gastl
authors.affiliation: Clinical Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Nachbaur
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine