Hyperleukocytosis is associated with distinct genetic alterations and is an independent poor-risk factor in de novo acute myeloid leukemia patients

Eur J Haematol. 2018 Jul;101(1):86-94. doi: 10.1111/ejh.13073. Epub 2018 May 22.

Abstract

Objectives: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited.

Methods: A total of 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications.

Results: Hyperleukocytosis, defined as initial white blood cell counts above 50 000/μL, occurred in 28.9% of AML patients. HL patients had higher incidences of FLT3-ITD, NPM1, DNMT3A, CEBPA, and TET2 mutations. Multivariate analysis demonstrated that HL was an independent poor prognostic factor for overall survival and disease-free survival in total patients, those with intermediate-risk cytogenetics and normal karyotype irrespective of genetic alterations. Intriguingly, HL predicted poor survival in CEBPA double mutated, NPM1 + /FLT3-ITD- and NPM1-/FLT3-ITD- patients. Further, HL patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR) had a significantly longer overall survival and disease-free survival than those without allo-HSCT.

Conclusions: Hyperleukocytosis is an independent poor prognostic factor irrespective of cytogenetics and mutation status. Allo-HSCT in first CR seems to ameliorate the poor prognostic impact of HL.

Keywords: acute myeloid leukemia; genetic alterations; hyperleukocytosis; prognosis; transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / immunology
  • Cohort Studies
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / immunology
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Dioxygenases
  • Female
  • Gene Expression Regulation, Leukemic*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Karyotyping
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Leukocytosis / diagnosis*
  • Leukocytosis / genetics
  • Leukocytosis / mortality
  • Leukocytosis / therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology
  • Nucleophosmin
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Remission Induction
  • Risk Factors
  • Survival Analysis
  • Transplantation, Homologous
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / immunology

Substances

  • Antineoplastic Agents
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • DNA-Binding Proteins
  • DNMT3A protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Nucleophosmin
  • Dioxygenases
  • TET2 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3