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1.
Clin Lymphoma Myeloma Leuk ; 13(2): 123-30, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23291040

ABSTRACT

UNLABELLED: Chromosomal aberrations are important prognostic factors in multiple myeloma diagnosis. We evaluated the effect common high-risk chromosomal aberrations in a cohort of 102 patients with relapsed disease treated with bortezomib or thalidomide. Our results showed that patients treated with thalidomide with a gain(1)(q21) had inferior survival compared with the bortezomib group. Therefore, bortezomib-based regiments are more effective for patients with relapsed multiple myeloma with an incidence of gain in the gain(1)(q21). BACKGROUND: Prognostic impact of specific chromosomal aberrations in patients with relapsed multiple myeloma (MM) treated with the novel agents is briefly described. PATIENTS AND METHODS: We analyzed the prognostic value of an extended panel of chromosomal aberrations [del(13)(q14), del(17)(p13), t(4;14)(p16;q32), gain(1)(q21), and hyperdiploidy] by using the technique of interphase fluorescence in situ hybridization in a cohort of 102 patients with relapsed MM treated with thalidomide- or bortezomib-based protocols. RESULTS: The gain(1)(q21) had a negative impact on overall survival for patients with MM treated with thalidomide (15.7 vs. 41.3 months; P = .004). Moreover, we confirmed the negative impact of the cumulative effect of 2 or more cytogenetic changes that occur simultaneously on the overall survival in the thalidomide group (20.3 months vs. not yet reached; P = .039). We did not find any significant impact of the aberrations studied on overall survival in the bortezomib cohort of patients. CONCLUSION: We conclude that bortezomib-based protocols are able to partially overcome the negative prognostic impact of the tested chromosomal abnormalities in patients with relapsed MM.


Subject(s)
Antineoplastic Agents/therapeutic use , Boronic Acids/therapeutic use , Chromosomes, Human, Pair 1 , Multiple Myeloma/drug therapy , Multiple Myeloma/genetics , Pyrazines/therapeutic use , Thalidomide/therapeutic use , Trisomy , Adult , Aged , Aged, 80 and over , Bortezomib , Chromosome Aberrations , Female , Humans , Incidence , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/pathology , Neoplasm Staging , Prognosis , Recurrence , Treatment Outcome
2.
Leuk Lymphoma ; 53(5): 920-7, 2012 May.
Article in English | MEDLINE | ID: mdl-22023516

ABSTRACT

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 ß(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.


Subject(s)
Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 4 , Karyotyping , Multiple Myeloma/genetics , Translocation, Genetic , Adult , Aged , Chromosome Aberrations , Cytogenetic Analysis , Female , Hematopoietic Stem Cell Transplantation , Humans , Incidence , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Prognosis , Survival Rate , Transplantation, Autologous
3.
Clin Lymphoma Myeloma Leuk ; 11(5): 414-20, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21859556

ABSTRACT

INTRODUCTION/BACKGROUND: Venous thromboembolism (VTE), with the subsequent risk of pulmonary embolism, is a common adverse effect of thalidomide treatment in patients with multiple myeloma (MM). In our retrospective study, we analyzed candidate single-nucleotide polymorphisms (SNP), CINP (rs7011), CETP (rs289747), ALDH1A1 (rs610529), CDKN1A (rs3829963), GAN (rs2608555), vascular endothelial growth factor (rs699947), and ALDH1A1 (rs168351), previously identified in a large association study based on the hypothesis-driven candidate gene approach nominated by the International Myeloma Foundation "Bank On A Cure" (3404 SNPs). In that study, the researchers built a classification tree that enables prediction of individual risk of VTE in patients with MM. PATIENTS AND METHODS: Genotypes of these SNPs were determined in an independent cohort of 111 patients with MM through TaqMan real-time polymerase chain reaction (PCR) allelic discrimination and were used for prediction of individual VTE risk. RESULTS: The results of this study did not confirm the ability of this classification tree to predict VTE risk in patients with MM from the Czech Republic; of these patients, 21 (19%) developed high-grade VTE. However, in patients with VTE, we found higher frequency of the AC genotype in the CDKN1A gene (42.9% vs. 16.7%; odds ratio 3.64) in comparison with the CC genotype (P = .015). SNPs of other genes as well as age and sex of the patients had no statistically significant influence on the risk of VTE. CONCLUSION: Further studies are needed to confirm the initial analysis that provided predictive information of genetic variations in patients with myeloma that may influence risk of VTE.


Subject(s)
Antineoplastic Agents/adverse effects , Multiple Myeloma/complications , Multiple Myeloma/genetics , Polymorphism, Single Nucleotide , Thalidomide/adverse effects , Venous Thromboembolism/etiology , Adult , Aged , Aged, 80 and over , Alleles , Antineoplastic Agents/administration & dosage , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Multiple Myeloma/drug therapy , Prognosis , Retrospective Studies , Risk , Thalidomide/administration & dosage , Venous Thromboembolism/diagnosis
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