Prognostic value of selected chromosomal abnormalities in multiple myeloma patients treated by thalidomide

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Authors

ZAORALOVÁ Romana GREŠLIKOVÁ Henrieta FILKOVÁ Hana NĚMEC Pavel KUGLÍK Petr OLTOVÁ Alexandra POUR Luděk ADAM Zdeněk KŘIVANOVÁ Andrea KREJČÍ Marta HÁJEK Roman

Year of publication 2007
Type Article in Proceedings
Conference Haematologica
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords Multiple myeloma; thalidomide; cIg FISH
Description The aim of this prospective study is to investigate if Thalidomide is able to antagonize the impact of cytogenetic negative prognostic markers. We have focused on four chromosomal aberrations known as negative prognostic factors in multiple myeloma (MM) treated by conventional or myeloablastive treatment: deletion of 13q14 (RB), deletion of 17p13 (p53), amplification of CKS1B gene (1q21) and translocation t(4;14). Material and Methods: For identification of malignant plasma cells in bone marrow samples, we use cytoplasmic immunoglobulin (cIg) labelling methodology. This method allows us to identify simultaneously monotypic plasma cells by monoclonal antibody fluorescence (anti-k or anti-l) and to detect chromosomal abnormalities by fluorescence in situ hybridization (cIg-FISH). Overall characteristics of up-to-date set of 24 patients (pts.): median age 65,0 years (range 48,3-83,3). 66% (16/24 pts.) in stage IIIA, 29% (7/24 pts.) in stage IIA and 1 patient in IIIB. 75% (16/24 pts.) were in first relapse; the others were in second relapse. Preliminary Results: Cytogenetic findings: Deletion of 13q14 was detected in 62% (13/21) pts., t(4;14) in 66% (14/21) pts., deletion of 17p13 in 41% (7/17) pts. and amplification of CKS1B gene in 63% (12/19) pts. Overall response (OR) was 83% (0% CR, 29% VGPR, 54% PR). OR was not significantly higher in pts. with or without cytogenetic findings for all aberration types. There were no difference when compared OS, TTP, PFS and DOR for groups with or without each aberration except deletion of RB gene or amplification of CKS1B: average OS was 10,2 (SD=3,4) months vs. 6,6 (SD=2,2) months in patients with vs. without the RB deletion and 7,1 (SD=3,1) vs. 10,0(SD=3,8) months for amplification of CKS1B. Conclusion: Despite of the observed trends in patients with CKS1B amplification or deletion of RB gene, we have found no significant difference when compared groups with or without of each aberration for TTP, DOR, PFS, OS and response rate. This should have been caused by small size of our sample. It is still possible that Thalidomide antagonizes the negative prognostic value of some cytogenetic findings in MM.
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