title: Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure.
abstract: We evaluated the impact of salvage regimens and allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) with induction failure. Between 1993 and 2009, 3324 patients with newly diagnosed AML were enrolled in 5 prospective treatment trials of the German-Austrian AML Study Group. After first induction therapy with idarubicin, cytarabine and etoposide (ICE), 845 patients had refractory disease. In addition, 180 patients, although responding to first induction, relapsed after second induction therapy. Of the 1025 patients with induction failure, 875 (median age 55 years) received intensive salvage therapy: 7+3-based (n=59), high-dose cytarabine combined with mitoxantrone (HAM; n=150), with all-trans retinoic acid (A; A-HAM) (n=247), with gemtuzumab ozogamicin and A (GO; GO-A-HAM) (n=140), other intensive regimens (n=165), experimental treatment (n=27) and direct allo-HCT (n=87). In patients receiving intensive salvage chemotherapy (n=761), response (complete remission/complete remission with incomplete hematological recovery (CR/CRi)) was associated with GO-A-HAM treatment (odds ratio (OR), 1.93; P=0.002), high-risk cytogenetics (OR, 0.62; P=0.006) and age (OR for a 10-year difference, 0.75; P<0.0001). Better survival probabilities were seen in an extended Cox regression model with time-dependent covariables in patients responding to salvage therapy (P<0.0001) and having the possibility to perform an allo-HCT (P<0.0001). FLT3 internal tandem duplication, mutated IDH1 and adverse cytogenetics were unfavorable factors for survival.
authors.affiliation: Kliniken Essen Süd, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wattad
authors.affiliation: University Hospital of Ulm, Ulm, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Weber
authors.affiliation: University Hospital of Ulm, Ulm, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Döhner
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krauter
authors.affiliation: University Hospital of Ulm, Ulm, Germany.
authors.forename: V I
authors.initials: VI
authors.lastname: Gaidzik
authors.affiliation: University Hospital of Ulm, Ulm, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Paschka
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Heuser
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Thol
authors.affiliation: University Medical Center of Mainz, Mainz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kindler
authors.affiliation: University Hospital of Freiburg, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lübbert
authors.affiliation: University Hospital of Tübingen, Tübingen, Germany.
authors.forename: H R
authors.initials: HR
authors.lastname: Salih
authors.affiliation: University Hospital of Düsseldorf, Düsseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kündgen
authors.affiliation: University Hospital of Kiel, Kiel, Germany.
authors.forename: H-A
authors.initials: HA
authors.lastname: Horst
authors.affiliation: University Hospital of Bonn, Bonn, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Brossart
authors.affiliation: University Hospital of München, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Götze
authors.affiliation: University Hospital of Innsbruck, Innsbruck, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Nachbaur
authors.affiliation: Klinikum Oldenburg, Oldenburg, Germany.
authors.forename: C-H
authors.initials: CH
authors.lastname: Köhne
authors.affiliation: Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ringhoffer
authors.affiliation: University Hospital of Göttingen, Göttingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wulf
authors.affiliation: University Hospital of Saarland, Homburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Held
authors.affiliation: Asklepios Klinik Altona, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Salwender
authors.affiliation: Division of Biostatistics, German Cancer Research Center Heidelberg, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Benner
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ganser
authors.affiliation: University Hospital of Ulm, Ulm, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.affiliation: University Hospital of Ulm, Ulm, Germany.|NCT Trial Center, National Center for Tumor Diseases (NCT), Heidelberg, Gemany.
authors.forename: R F
authors.initials: RF
authors.lastname: Schlenk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult