Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial
| Authors | |
|---|---|
| Year of publication | 2012 |
| Type | Article in Periodical |
| Magazine / Source | Leukemia & Lymphoma |
| MU Faculty or unit | |
| 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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