Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial.
The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11;14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and β(2)-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with ≤ 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation.
Department of Pathological Physiology, Masaryk University, Brno, Czech Republic.
Pavel
P
Nemec
Zuzana
Z
Zemanova
Petr
P
Kuglik
Kyra
K
Michalova
Jana
J
Tajtlova
Petra
P
Kaisarova
Alexandra
A
Oltova
Hana
H
Filkova
Milena
M
Holzerova
Jana
J
Balcarkova
Marie
M
Jarosova
Jana
J
Rabasova
Martina
M
Hruba
Ivan
I
Spicka
Evzen
E
Gregora
Zdenek
Z
Adam
Vlastimil
V
Scudla
Vladimir
V
Maisnar
Miroslava
M
Schutzova
Roman
R
Hajek
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D020732:Cytogenetic Analysis; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate; D014178:Translocation, Genetic; D014182:Transplantation, Autologous