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Comparison of prognostic impact of chromosome 1q21 gain in patients with multiple myeloma treated by Velcade, thalidomide and any conventional therapy

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Original title:Comparison of prognostic impact of chromosome 1q21 gain in patients with multiple myeloma treated by Velcade, thalidomide and any conventional therapy
Authors:Pavel Němec, Henrieta Grešliková, Romana Zaoralová, Hana Filková, Vladimíra Vranová, Renata Kupská, Jana Smejkalová, Alexandra Oltová, Petr Kuglík, Roman Hájek
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Original language:English
Field:Genetics and molecular biology
Type:Article in Proceedings
Keywords:multiple myeloma; 1q21 gain; Velcade; thalidomide; fluorescence in situ hybridisation

Background Amplification of chromosome band 1q21 as well as increased expression of CKS1B gene in this area is a frequently mentioned prognostic factor for patients with multiple myeloma (MM). Aims This study was aimed at comparison of prognostic impact of 1q21 gain in three selected groups of patients with diagnosed MM based on treatment regiment. Methods Plasma cells were identified by cytoplasmic light-chain fluorescence in situ hybridisation (cIg-FISH), 1q21 amplification (Amp1q21) utilizing the 1q21/1p36 DNA probe. Amp1q21 was taken such as detection of one or more additional signals of 1q21 DNA probe. Cut-off level for Amp1q21 was established to 20% of total amount of cells with additional signals detected. Patients with Amp1q21 and patients lacking Amp1q21 of each group were statistically correlated with clinical parameters. Up to date we have carried out analysis of 66 (n=66) patients. This group of patients with median of follow up 8,6 months (range: 0,3-30,4) was divided according to the undergone therapy into 3 groups: "C-group" comprises 17 samples of patients treated by any conventional therapy; "T-group" comprises 27 samples of patients treated by thalidomide; "V-group" comprises 22 samples of patients treated by Velcade. The response and other parameters such as time to progression (TTP) and overall survival (OS) were assigned by IMWG criteria. Results Amp1q21 was found in 62.1% of all 66 patients. Percentage of patients with Amp1q21 in C/T/V-groups were as follows: 64.7% / 40.7% / 86.4%, respectively. Clinical parameters valid for patients with Amp1q21 (listed in C/T/V order) were as follows: overall response rate (ORR) 42.8% / 83.3% / 50%; TTP 8.8 / 12.1 / 8.0 months; OS 16.1 / 6.6 / not yet reached for V-group. The same parameters valid for patients lacking Amp1q21: ORR 33.3% / 80% / 66.7%; TTP not yet reached for C-group / 8.2 / not yet reached for V-group; OS not yet reached for all groups. TTP median of patients with Amp1q21 vs. patients lacking 1q21 was: 8.2 vs. 12.1 months (p=0.269), OS 6.6 vs. not yet reached (p=0,072) in thalidomide group. We didn't find any other significant differences between patients with / without Amp1q21 and their parameters in V- and C-group. Summary / Conclusions Our results suggest that patients with Amp1q21 treated by thalidomide show a trend towards the worst prognosis based on overall survival. We are currently investigating whether or not our findings will be confirmed on a larger cohort of patients with longer follow-up. Supported by Monoclonal Gammopathy and Multiple Myeloma Basic Research Centre (LC 06027), Masaryk University, Czech republic.

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