Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.
OBJECTIVE
Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations.


METHODS
Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed.


RESULTS
By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P =.006 and 40.0% v 73.2%, P =.008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P =. 008 and 16.2 v 51.3 months, P =.008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P =.02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P <.001, respectively).


CONCLUSIONS
For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.
Königsberg
R
R
First Department of Internal Medicine, Divisions of Clinical Oncology, University of Vienna, Vienna, Austria.
Zojer
N
N
Ackermann
J
J
Krömer
E
E
Kittler
H
H
Fritz
E
E
Kaufmann
H
H
Nösslinger
T
T
Riedl
L
L
Gisslinger
H
H
Jäger
U
U
Simonitsch
I
I
Heinz
R
R
Ludwig
H
H
Huber
H
H
Drach
J
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003582:Cytogenetics; D005260:Female; D005544:Forecasting; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D007399:Interphase / Q000235:genetics*; D008297:Male; D008677:Metaphase / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015999:Multivariate Analysis; D010950:Plasma Cells / Q000473:pathology; D011379:Prognosis; D012044:Regression Analysis; D012074:Remission Induction; D015996:Survival Rate; D014314:Trisomy / Q000235:genetics