title: High-dose cytarabine as salvage therapy for relapsed or refractory acute myeloid leukemia--is more better or more of the same?
abstract: Cytarabine is the backbone of most chemotherapeutic regimens for acute myeloid leukemia (AML), yet the optimal dose for salvage therapy of refractory or relapsed AML (RR-AML) has not been established. Very high dose single-agent cytarabine at 36 g/m(2) (ARA-36) was previously shown to be effective and tolerable in RR-AML. In this retrospective analysis, we aim to describe the toxicity and efficacy of ARA-36 as salvage therapy for patients with AML who are primary refractory to intensive daunorubicin-containing induction or those relapsing after allogeneic stem cell transplant (alloSCT). Fifteen patients, median age 53 years, were included in the analysis. Six patients were treated for induction failure, one had resistant APL, and eight relapsed after alloSCT. Complete remission was achieved in 60% of patients. Surviving patients were followed for a median of 8.5 months. One-year overall survival was 54% (95% CI 30%-86%), and relapse rate from remission (n = 9) was 56%. Grade III/IV pulmonary, infectious, ocular and gastrointestinal toxicities occurred in 26%, 20%, 20% and 20% of patients respectively. Salvage therapy with ARA-36 regimen for RR-AML has considerable efficacy with manageable toxicity in patients with induction failure or post-transplant relapse. Overall survival in these high-risk patients still remains poor.
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofir
authors.initials: O
authors.lastname: Wolach
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Itchaki
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Bar-Natan
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Yeshurun
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Ram
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Corina
authors.initials: C
authors.lastname: Herscovici
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.affiliation: Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Douer
authors.affiliation: Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D007634:Keratitis / Q000139:chemically induced; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome; D014985:Xerophthalmia / Q000139:chemically induced; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine
keywords: high-dose cytarabine; refractory AML; relapsed AML