title: 5-Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy.
abstract: Despite progress in the understanding of leukemia pathophysiology, the treatment of acute myeloid leukemia (AML) remains challenging. In patients with refractory or relapsed (R/R) AML, the prognosis is still poor and this group is targeted for new drug development. We reviewed the outcome of 47 patients, with R/R AML after at least one course of intensive chemotherapy, treated with 5-azacytidine in three different French institutions. The overall response rate was 38% including complete remission in 21%, partial remission in 11%, and hematological improvement in 6% of cases. Median time to relapse was 6 (range, 1-39) months. Median overall survival was 9 months (not reached by responders vs. 4.5 months for nonresponders patients, P = 0.0001). Univariate analysis identified the absence of peripheral blood blasts and <20% bone marrow blasts as prognostic factors for both overall response and survival, but not age, ECOG/PS, type of AML, cytogenetic, status of the disease, number of previous lines of therapy, previous hematological stem cell transplantation, or white blood cells count. Bone marrow blasts percentage <20% was the only independent prognostic factor identified by multivariate analysis for overall response (P = 0.0013) and survival (P = 0.0324). Six patients in remission could proceed to an allogenic hematological stem cell transplantation. The drug-related grade 3/4 adverse events were hematopoietic toxicities (38%) and infection (32%). In conclusion, this study suggests that a salvage therapy with 5-azacytidine is an interesting option for patients with R/R AML after intensive chemotherapy. Prospective randomized studies are needed to demonstrate a superiority of this approach over others strategies.
authors.affiliation: Service d'Hématologie Clinique, CHU Amiens, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ivanoff
authors.forename: Berengere
authors.initials: B
authors.lastname: Gruson
authors.forename: Sylvain P
authors.initials: SP
authors.lastname: Chantepie
authors.forename: Emilie
authors.initials: E
authors.lastname: Lemasle
authors.forename: Lavinia
authors.initials: L
authors.lastname: Merlusca
authors.forename: Veronique
authors.initials: V
authors.lastname: Harrivel
authors.forename: Amandine
authors.initials: A
authors.lastname: Charbonnier
authors.forename: Patrick
authors.initials: P
authors.lastname: Votte
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001374:Azacitidine / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D001374:Azacitidine