Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS

Leuk Res. 2015 Oct;39(10):1079-87. doi: 10.1016/j.leukres.2015.06.011. Epub 2015 Jun 28.

Abstract

We genetically analyzed a group of high risk MDS/AML patients treated by a combination of azacitidine and lenalidomide. In our cohort, the extent of genetic rearrangements was associated with outcome and response to treatment. The size of total genomic aberrations as defined by molecular karyotyping (SNP-array analysis) was a predictive marker for overall survival. TP53 mutations were associated with therapy refractoriness only if accompanied by heavily rearranged chromosomes. This study suggests a potential value of molecular karyotyping as a method to objectivate comprehensively the extent of genetic alterations in high risk patients with complex karyotypes, especially if the clinical value of the size of total genomic aberrations and the fragmentation status of single chromosomes could be evaluated in larger therapy trials.

Keywords: AML; Cytogenetics; FISH; MDS; SNP arrays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / administration & dosage
  • Chromosome Aberrations
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Karyotyping / methods*
  • Lenalidomide
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / genetics
  • Oligonucleotide Array Sequence Analysis
  • Proportional Hazards Models
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53
  • Thalidomide
  • Lenalidomide
  • Azacitidine