The Significance Of Fluorescence In Situ Hybridization&International Staging System On Clinical Treatment And Prognosis Of Multiple Myeloma

【Objective】To study the genetic changes in patients with multiple myeloma cells,FISH detection tests of molecular cytogenetics changes1q21amplification, loss of P53,RB1,13q14, IgH rearrangement probability and the ratio of the patients with multiplemyeloma, biology index relations with poor prognosis, the relationship betweenchromosome abnormality and survival period, the influence of different treatments of PFS,OS, as well as the ISS stage effect on PFS, OS, etc. The clinical treatment of multiplemyeloma selection and adverse prognostic factors were analyzed, and developed a set ofsuitable for clinical treatment.【Methods】Retrospective analysis, this study from January2008to February2008in ourhospital blood disease research center for treatment of109patients with multiple myelomaspecimens were studied. Using traditional chromosome detection and fluorescence in situhybridization (FISH) technology to detect109cases of patients with MM, the biologicalindicator and different treatment methods for statistical analysis, observe its chromosomes,FISH anomalies, ISS stage of PFS, OS, the chromosome and FISH test results for theeffect of clinical treatment and prognosis of multiple myeloma.【Results】The study of109cases, follow-up time until May31,2014, the medianfollow-up time14months (1~73months).1.Conventional cytogenetic chromosome abnormality109first time patients overalldetection rate was27.5%(30/109); Test positive for FISH (>10%，of which P53＞30%)of the total detection rate was47.7%(52/109), of which13q14lack, lack of Rb1, loss ofP53,1q21amplification, IgH rearrangement is respectively25.7%,26.6%,2.8%,30.3%and28.4%, respectively. According to FISH the detection positive rate is a traditional cell karyotype detection nearly2times.2.Based on109cases of age, gender, platelet, hemoglobin, serum calcium, serumcreatinine, plasma cells, bone marrow, blood beta2micro globulin, albumin, LDH,different parting a series of index on the basis of calculating the survival time of patients,after the single factor analysis found that serum calcium concentration or greater tendencyfor≥3mmol/L, blood beta2microglobulin acuity≥5.5mg/L, albumin <35g/L is the majoradverse prognostic factors affecting the prognosis of patients survival (P <0.05).3.After109cases of patients with normal karyotype analysis, normal karyotype groupmedian PFS, OS time42months, respectively,73months, abnormal karyotype group hasnot yet appeared in a time of PFS, the median OS32months, abnormal karyotype thannormal karyotype the median OS shorter time (P=0.083); Abnormal karyotype inhigh-risk karyotype group (including the diploid,13-17P/q-13and17-/-) cases in23cases, among them a PFS, OS time24months,32months, respectively, than normalkaryotype time significantly shortened (P values were0.110,0.017); Karyotype of showabnormal karyotype is particularly high risk associated with poor outcome. Chromosome13missing15cases, in which a PFS, OS time seven months,28months, respectively, thannormal karyotype time significantly shortened (P values were0.003,0.001), promptedchromosome13missing poor prognosis.4.FISH all negative57cases, the median PFS, OS time42months,73months,respectively; Contrast found that13q14lack positive28cases, the median PFS, OS timefor11months,28months respectively, the FISH negative time shorten (P values were0.023,0.001); RB1lack positive29cases, the median PFS, OS time for11months,28months respectively, the FISH negative time shorten (P values were0.049,0.003); Lack ofP53positive3cases, the median PFS, OS time7months,13months, respectively, theFISH negative time shorten (P values were0.144,0.019);1q21amplification positive33cases, the median PFS, OS and21months respectively,47months time, the FISH negativetime shorten (P values were0.125,0.084); IgH rearrangement positive31cases, themedian PFS, OS time24months,47months, respectively, the FISH negative time shorten(P values were0.285,0.174). FISH more positive, a total of33cases (two or higher), andthe median PFS time did not appear, the median OS time47months, respectively, the FISHnegative time shorten (P values were0.127,0.015).5.Chromosomal abnormalities30cases according to whether the use of boron for induction therapy for PFS, OS compared with m, the use of boron for m treatment of18cases,12cases of boron for Mr M treatment, the former median PFS, OS time did notappear, the latter the median PFS, OS time9months,32months, respectively, after boronthan patients who were not used for induction therapy with m obviously prolong themedian survival time (P values were0.142,0.462). Also will chromosomes of79cases ofnormal according to whether or not to use for boron with m induction therapy for PFS, OScomparison, the use of boron for m treatment of45cases, the boron for m treatment of34cases, the former median PFS21months, the median OS time has not yet appeared; Themedian PFS, OS time42months,73months, respectively; After boron for zc metersinduction therapy than patients who were not using the median survival time has noobvious extended (P values were0.075,0.053). After boron for zc meters after inductiontherapy, chromosome abnormality big benefit from the group of patients in the normalgroup, significantly prolong the median survival time, prove that boron for zc meters in thepoor prognosis of chromosomal abnormalities of the MM treatment has obviousadvantages.6.Chromosomal abnormalities30cases according to whether the PFS, OS comparisonof transplantation, the transplant the treatment of11cases of not using transplantation of19cases, the former median PFS, OS time did not appear, the latter the median PFS, OStime also does not appear, chromosome abnormality case for using transplantation therapyfor patients with a median survival time has no obvious influence (P values were0.829,0.608). Also will chromosomes of79cases of normal according to whether transplantationPFS, OS comparison, using transplantation of29cases, not the transplantation of thetreatment of50cases of median PFS, OS time did not appear, the latter the median PFS,OS time of19months,73months, respectively, using transplantation after treatment thanpatients who were not used significantly prolong the median survival time (P values were0.024,0.021). Use after transplantation, normal chromosome group a chromosomeabnormality patients benefit, significantly prolong the median survival time. Provetransplantation treatment on chromosome normal prognosis is good in MM treatment hasobvious advantages.7.According to the ISS staging criteria classification, stage I22cases,40cases instage II, III47cases;109cases CR69, PR1, VGPR15example, SD24example, the totaleffective rate was77.98%. According to the ISS stage different survival curve drawing, I in the mid-term PFS, OS time does not appear; II the mid-term PFS24months, the medianOS time has not yet appeared; III the mid-term PFS, OS time17months,37months,respectively, in installment level, the higher the curative effect is poorer, the lower survivalrate (P values were0.022,0.010).8.Risk stratification in FISH test results combined with ISS in installment.Groupstandard: Riskgroup: All cases besides high-risk group; High-risk group: All FISH-IIIstage cases, ISS-II stage cases with at least2project of FISH(+) or P53-lack(+)[13q14-lack(+) and Rb1-lack(+) was defined as one positive project]. Divided into the riskgroup of47cases and high-risk group of62cases, the former median PFS, OS time doesnot appear; The median PFS, OS time17months,47months, respectively, the crisisrelatively high-risk group significantly prolong the median survival time (P values were0.001,0.001).Transplantation cases in40cases, transplantation cases69cases; The former markwei group (19cases), high-risk group of21cases; The latter dangerous group of28cases,high-risk group of41cases. Compared to the non-transplanted group, two groups oftreatment group, the crisis in the group, the median PFS, OS time did not appear, the latteralso does not appear, whether to adopt the intermediate risk category had a transplanttreatment of the median survival time did not see obvious difference; High-risk groups, theformer median PFS, OS time did not appear, the latter the median PFS, OS time17months,47months, respectively, the high-risk group treatment is not to transplant the median PFS,OS obviously prolonged (P values were0.001,0.002), transplantation might be of benefitin high-risk group of patients.The transplantation cases69cases,39cases with boron for m treatment, other30cases are using normal chemotherapy treatment. The former label dangerous group of15cases, high-risk group of24cases; The latter dangerous group of13cases of high riskgroup of17cases. Comparing boron for Mr M group and common chemotherapy treatmentin both groups, the crisis group, the former median PFS, OS time did not appear, the latteralso does not appear, the dangerous groups choose different treatment median PFS, OS didnot see obvious difference; High-risk groups, the former median PFS, OS time and21months respectively,47months; The median PFS, OS time for five months and21monthsrespectively, high-risk groups treated relatively common choice for boron with m aneffective chemotherapy median PFS, OS (P values were0.000,0.014), boron for rice might be of benefit in high-risk group of patients is larger.Accordingly to the Fish ISS stage of risk stratification for prognosis and treatmentoptions.【conclusion】The study of109cases, follow-up time until May31,2014, the medianfollow-up time14months (1~73months).1. For patients with multiple myeloma, using conventional karyotype analysis and FISHtechnology to detect cell genetics, chromosome abnormality as the main characteristicsof abnormal karyotype karyotype of high risk associated with poor outcome, especiallylack of chromosome13prognosis.2. FISH more positive than FISH all negative the median survival time were shortened,are associated with poor outcome.3. After boron for induction therapy with bortezomib, chromosome abnormality thannormal group of patients benefit from greater; Adopt transplantation therapy, normalchromosome group is abnormal patients benefit more.4. ISS stage, according to the results of stage level, the higher the worse curative effect,the lower the survival rate. Risk stratification in FISH test results combined with ISS ininstallment, the risk in the high-risk group obviously prolong surial time; In thetreatment of choice, for transplantation therapy and boron with m helps to high-riskgroup of patients have more chances of survival.