Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

Haematologica. 2013 Apr;98(4):649-54. doi: 10.3324/haematol.2012.070458. Epub 2012 Oct 12.

Abstract

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.

Trial registration: ClinicalTrials.gov NCT00566332 NCT00608374.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Chlorambucil / therapeutic use
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 4 / genetics
  • Chromosomes, Human, Pair 6 / genetics
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Karyotype
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Trisomy
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Waldenstrom Macroglobulinemia / drug therapy
  • Waldenstrom Macroglobulinemia / genetics*
  • Waldenstrom Macroglobulinemia / pathology

Substances

  • Antineoplastic Agents
  • Chlorambucil
  • Vidarabine
  • fludarabine

Associated data

  • ClinicalTrials.gov/NCT00566332
  • ClinicalTrials.gov/NCT00608374