Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial

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Authors

NĚMEC Pavel ZEMANOVA Zuzana KUGLÍK Petr MICHALOVÁ Kyra TAJTLOVA Jana KAISAROVÁ Petra OLTOVA Alexandra FILKOVÁ Hana HOLZEROVÁ Milena BALCÁRKOVÁ Jana JAROSOVA Marie BARABÁŠOVÁ Jana HRUBANOVÁ Martina SPICKA Ivan GREGORA Evzen ADAM Zdeněk ŠČUDLA Vlastimil MAISNAR Vladimír SCHUTZOVA Miroslava HÁJEK Roman

Year of publication 2012
Type Article in Periodical
Magazine / Source Leukemia & Lymphoma
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.3109/10428194.2011.634042
Field Neurology, neurosurgery, neurosciences
Keywords Multiple myeloma; chromosomal abnormalities; prognostic factors; stem cell transplantation; cytogenetics and molecular genetics
Description 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 beta(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.
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