Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy.
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.
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. gertz.morie@mayo.edu
Morie A
MA
Gertz
Martha Q
MQ
Lacy
Angela
A
Dispenzieri
Philip R
PR
Greipp
Mark R
MR
Litzow
Kimberly J
KJ
Henderson
Scott A
SA
Van Wier
Greg J
GJ
Ahmann
Rafael
R
Fonseca
D000328:Adult; D000368:Aged; D002877:Chromosomes, Human / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53