title: Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT.
abstract: Despite the overall benefit from allogeneic hematopoietic stem cell transplantation observed in patients with poor cytogenetic risk acute myeloid leukemia in first complete remission, the precise effect of this procedure for different poor-risk subtypes has not been fully analyzed. This retrospective analysis was performed to investigate whether allogeneic hematopoietic stem cell transplantation performed in first complete remission in patients with monosomal karyotype can overcome the adverse prognosis associated with these patients. Of the 4635 patients included in the study, 189 (4%) harbored a monosomal karyotype. The presence of a monosomal karyotype was associated with a worse outcome, with an inferior leukemia-free survival and overall survival (5-year leukemia-free survival and overall survival: 24 ± 3% and 26 ± 3% vs. 53 ± 1% and 57 ± 1% in monosomal-karyotype and non-monosomal-karyotype, respectively; P<0.0001) and higher relapse risk after transplantation (cumulative incidence of relapse at 5 years: 56 ± 4% in monosomal-karyotype vs. 28 ± 1% in non-monosomal-karyotype; P<0.0001). The adverse negative impact of monosomal karyotype cytogenetics was confirmed in the entire cohort in a multivariate analysis [Hazard Ratio (HR): 1.88, 95% Confidence Interval (CI):1.29-2.73, P=0.001 for relapse incidence; HR:1.71, 95%CI:1.27-2.32, P<0.0001 for leukemia-free survival; HR:1.81, 95%CI:1.32-2.48, P=0.0002 for overall survival], and was independent of the presence of other poor-risk cytogenetic subtypes. In summary, monosomal karyotype arises as a strong negative prognostic feature in acute myeloid leukemia also in patients who undergo allogeneic hematopoietic stem cell transplantation in first complete remission, stressing the need to develop additional pre- and post-transplantation strategies aimed at improving overall results. Nonetheless, allogeneic hematopoietic stem cell transplantation in early phase is currently the best therapy for this very poor-risk acute myeloid leukemia subtype.
authors.affiliation: Catharina Ziekenhuis Eindhoven, Department of Internal Medicine, Division of Hematology, Eindhoven, the Netherlands.
authors.forename: Angelique V M
authors.initials: AV
authors.lastname: Brands-Nijenhuis
authors.affiliation: EBMT Data Office Paris, Hospital Saint Antoine, Department of Hematology, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Maastricht University Medical Center, the Netherlands.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.affiliation: Helsinki University Central Hospital, Department of Medicine, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Volin
authors.affiliation: Hospital St. Louis, Department of Hematology, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Erasmus Medical Center Rotterdam, the Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.affiliation: Hôpital de Purpan CHU Department Hematologie Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Karolinska University Hospital, Department of Hematology, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.affiliation: Hospital Saint Antoine, Department of Hematology, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.affiliation: Hospital Clínic, Department of Hematology, IDIBAPS, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.affiliation: Chaim Sheba Medical Center, Tel-Hashomer, Israel EBMT Data Office Paris, Hospital Saint Antoine, Department of Hematology, France.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Hospital Saint Antoine, Department of Hematology, Paris, France mohamad.mohty@inserm.fr.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009006:Monosomy / Q000473:pathology*; D015999:Multivariate Analysis; D011379:Prognosis; D012008:Recurrence; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents