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The Cytogenetic Abnormalities And Prognostic Analysis Of87Newly Diagnosed Multiple Myeloma

Posted on:2016-09-30Degree:MasterType:Thesis
Country:ChinaCandidate:J C ChenFull Text:PDF
GTID:2284330467999247Subject:Internal medicine
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Background and aim:Multiple myeloma (MM) is characterized by the clonal proliferation ofplasma cells and the subsequent accumulation of these cells within the bonemarrow. The prognosis of patients with MM is variable, with survival timesranging between a few months and>10years.Over the past few years, one ormore new agents have been incorporated into the treatment paradigm of patientswith MM, increasing survival rates of MM patients. Despite the recentapplication of novel drugs in clinical practice, MM remains incurable. Geneticabnormalities in patients with multiple myeloma (MM) are important riskfactors in terms of prognosis. FISH is the most useful current cytogeneticassessment.In the present study, the prognostic value of several common MM geneticabnormalities was investigated. We reviewed patients with MM in order toassess the incidence of genetic abnormalities and their associations with clinicalparameters, response of treatment, and prognosis. Methods:This was a retrospective study. A total of87newly diagnosed patients withMM who visited our Oncology Department, the First Hospital of Jilin Universityfrom November,2009to November,2014were enrolled. The incidences ofgenetic abnormalities were determined in all patients. FISH analysis wasperformed on four specific probes for the regions containing13q14(RB-1/D13S319),14q32(1GH),17p13(p53) and1q21.And the FlSHstudies with LSI lGH/CCNDl,LSI lGH/FGFR3,LSI IGH/MAF probes wereused to detect t(11;14)(q13;q32),t(4;14)(p16;q32) and t(14;16)(q32;q23) in partof patients with14q32rearrangement. The relationships of the geneticabnormalities and clinical parameters were investigated. In addition, a survivalanalysis was performed.Results:1. Of the87newly diagnosed patients investigated by FISH, molecularcytogenetic aberrations were found in67(76%) patients.IGH rearrangement,13q deletions,17p deletions, chromosome1q amplification were observed in42(48.3%),48(55.2%),12(13.8%) and45(51.7%) cases.2. High plasma cell burden was associated with13q deletions and IGHrearrangement (P=0.001vs P=0.012).3. Bortezomib could significantly improve the short-term effect of patientswith IGH rearrangement(P=0.046).The efficiency of13q deletions ofBortezomib is higher than traditional treatment(68.8%vs37.5%),while there was no statistical difference. Bortezomib can not imporve the short-term effectof17p delations and1q deletions.Compared with traditional chemotherapy,Bortezomib treatment could prolong the OS of IGH rearrangement,13qdeletions, chromosome1q amplification and the PFS of IGH rearrangement andchromosome1q amplification,while there were no statistical differences.4. In univariate analysis, the significant factors of OS were17pdelations,IGH rearrangement and high plasma cell burden(P=0.006vs P=0.003vs P=0.001). And the significant factors of PFS were13q deletions and highplasma cell burden (P=0.024vs P=0.004).With multivariate analysis, thesignificant factor of OS was17p delations (P=0.047).Conclusions:1. Genetic abnormalities of MM are often high incidence and complicated.2. Bortezomib can improve the short-term effect of patients with IGHrearrangement and1q amplication and the long-term effect of IGHrearrangement,13q deletions and1q amplication.3. In univariate analysis, the significant factors of OS are17pdelations,IGH rearrangement and high plasma cell burden.And the significantfactors of PFS are13q deletions and high plasma cell burden.With multivariateanalysis, the significant factor of OS is17p delations.4.When the patients are newly diagnosed, cytogenetic abnormalities shouldbe detected.Patients should be treated depending on the cytogenetic abnormalities results,which is responsible for a better prognosis.
Keywords/Search Tags:Multiple myeloma, FISH, cytogenetic, prognosis, Bortezomib
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