Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype
Frédéric Baron,
Marian Stevens-Kroef,
Michal Kicinski,
Giovanna Meloni,
Petra Muus,
Jean-Pierre Marie,
Constantijn J.M. Halkes,
Xavier Thomas,
Radovan Vrhovac,
Francesco Albano,
François Lefrère,
Simona Sica,
Marco Mancini,
Adriano Venditti,
Anne Hagemeijer,
Joop H. Jansen,
Sergio Amadori,
Theo de Witte,
Roelof Willemze,
Stefan Suciu
Affiliations
Frédéric Baron
Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), Laboratory of Hematology, University of Liege, Belgium
Marian Stevens-Kroef
Radboud University Medical Center, Nijmegen, the Netherlands
Michal Kicinski
EORTC Headquarters, Brussels, Belgium
Giovanna Meloni
Department of Hematology, Sapienza University, Rome, Italy
Petra Muus
Radboud University Medical Center, Nijmegen, the Netherlands;King’s College Hospital, London, UK
Jean-Pierre Marie
Department of Hematology, Saint Antoine Hospital, Paris, France
Constantijn J.M. Halkes
Leiden University Medical Center, the Netherlands
Xavier Thomas
CHU Lyon, France
Radovan Vrhovac
University Hospital Center Zagreb, Croatia
Francesco Albano
University of Bari, Italy
François Lefrère
Necker Hospital, Paris, France
Simona Sica
Università Cattolica Sacro Cuore, Roma, Italy
Marco Mancini
Department of Hematology, Sapienza University, Rome, Italy
Adriano Venditti
University Tor Vergata, Roma, Italy
Anne Hagemeijer
University of Leuven, Belgium
Joop H. Jansen
Radboud University Medical Center, Nijmegen, the Netherlands
Sergio Amadori
University Tor Vergata, Roma, Italy
Theo de Witte
Radboud University Medical Center, Nijmegen, the Netherlands
Monosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were randomized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy. In the second trial patients were randomized to standard-dose cytarabine or high-dose cytarabine induction, both with daunorubicin and etoposide. In both trials, patients who achieved a complete remission with or without complete hematologic recovery underwent allogeneic hematopoietic stem cell transplantation if they had a donor; otherwise, they underwent autologous transplantation. In comparison to patients with intermediate-risk cytogenetics without a monosomal karyotype (n=1,584) and with adverse cytogenetics without a monosomal karyotype (n=218), patients with a monosomal karyotype (n=188) were more likely not to achieve a complete remission with or without count recovery [odds ratio=2.85, 95% confidence interval (95%, CI): 2.10-3.88] and had shorter overall survival [hazard ratio, (HR)=2.44, 95% CI: 2.08-2.88]. There was no impact of the type of anthracycline or of the dose of cytarabine on outcomes in patients with a monosomal karyotype. Among monosomal karyo type patients who achieved a complete remission with or without count recovery, HLA-identical related donor availability was associated with longer survival from complete remission with or without count recovery (HR=0.59, 95% CI: 0.37-0.95). ClinicalTrials.gov identifiers: AML-10: NCT00002549; AML-12: NCT00004128.
