title: Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse.
abstract: Based on molecular aberrations, in particular the NPM1 mutation (NPM1(mut)) and the FLT3 internal tandem duplication (Flt3-ITD), prognostic subgroups have been defined among patients with acute myeloid leukemia with normal karyotype. Whereas these subgroups are known to play an important role in outcome in first complete remission, and also in the indication for allogeneic stem cell transplantation, data are limited on their role after transplantation in advanced disease. To evaluate the role of molecular subgroups of acute myeloid leukemia with normal karyotype after allogeneic stem cell transplantation beyond first complete remission, we analyzed the data from 141 consecutive adults (median age: 51.0 years, range 18.4-69.3 years) who had received an allogeneic transplant either in primary induction failure or beyond first complete remission. A sequential regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine) followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for conditioning. After a median follow up of three years, overall survival from transplantation was 64 ± 4%, 53 ± 4% and 44 ± 5% at one, two and four years, respectively. Forty patients transplanted in primary induction failure achieved an encouraging 2-year survival of 69%. Among 101 patients transplanted beyond first complete remission, 2-year survival was 81% among patients with the NPM1(mut)/FLT3(wt) genotype in contrast to 43% in other genotypes. Higher numbers of transfused CD34(+) cells (hazard ratio 2.155, 95% confidence interval 0.263-0.964, P=0.039) and favorable genotype (hazard ratio 0.142, 95% confidence interval: 0.19-0.898, P=0.048) were associated with superior overall survival in multivariate analysis. In conclusion, patients with acute myeloid leukemia with normal karyotype can frequently be rescued after primary induction failure by allogeneic transplantation following FLAMSA-RIC. The prognostic role of NPM1(mut)/FLT3-ITD based subgroups was carried through after allogeneic stem cell transplantation beyond first complete remission.
authors.affiliation: Department of Hematology and Oncology, Klinikum Augsburg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Pfeiffer
authors.forename: Michael
authors.initials: M
authors.lastname: Schleuning
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Haude
authors.forename: Johanna
authors.initials: J
authors.lastname: Tischer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Buchholz
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
authors.forename: Maximilian
authors.initials: M
authors.lastname: Christopeit
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Jan
authors.initials: J
authors.lastname: Braess
authors.forename: Günter
authors.initials: G
authors.lastname: Schlimok
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D059785:Karyotype; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3