Haematologica (Jun 2019)

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

DOI
https://doi.org/10.3324/haematol.2018.204826
Journal volume & issue
Vol. 104, no. 6

Abstract

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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.