Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy

Blood. 2005 Oct 15;106(8):2837-40. doi: 10.1182/blood-2005-04-1411. Epub 2005 Jun 23.

Abstract

Fluorescence in situ hybridization (FISH) is more sensitive than conventional cytogenetics for recognizing chromosomal changes. Several FISH-detected abnormalities have been associated with inferior prognosis, including deletion of chromosomes 17 and 13 (Delta13) and t(4;14)(p16.3;q32). We analyzed the prognostic value of FISH testing in 238 patients who received high-dose therapy between January 1990 and September 2001. All patients had pretransplantation cytoplasmic immunoglobulin FISH done on cytospin slides from bone marrow aspirates for t(11;14), t(4;14), and -17(p13.1) (TP53). Time to progression and overall survival were significantly shorter for patients with t(4;14) and those with -17(p13.1) but were not affected by t(11;14). Overall survival was significantly shorter for patients with both t(4;14) and Delta13 abnormalities than for those with Delta13 alone (26.8 vs 18.8 months). In a multivariable analysis of the effect of Delta13 and t(4;14), the risk ratio for t(4;14) was greater than for Delta13 (2.6 vs 1.5). For high-dose therapy patients, -17(p13) and t(4;14) have clinical importance for estimating time to progression and overall survival. The presence of t(4;14) identifies a subset of patients whose time to progression is only 8.2 months. These patients receive minimal benefit from autologous stem cell transplantation and are candidates for novel therapeutic approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Chromosomes, Human / genetics*
  • Disease Progression
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics*
  • Prognosis
  • Survival Rate
  • Translocation, Genetic / genetics*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53