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1.
 目的 探讨应用流式细胞术(FCM)检测急性白血病(AL)患者骨髓微小残留病(MRD)对预测复发及指导治疗的临床意义。方法 选择2005年7月至2008年6月于该院住院经MIC分型确诊的初治获完全缓解(CR)的43例AL患者,应用FCM和单克隆抗体直接荧光标记法检测骨髓MRD,并动态随访。结果 对初次受检MRD阳性患者动态观察骨髓形态学,平均1~3个月复查骨髓1次,所有复发患者均在MRD阳性后4~6个月出现形态学复发。MRD随访结果显示:43例AL患者CR时MRD阴性26例,6例复发,持续阴性20例。CR时MRD阳性17例,10例复发(58.82 %)。4例经加强化疗后MRD转阴达1年以上。43例患者CR时按MRD值水平分为三组,并观察1年复发率。<1×10-4组和5×10-3~1×10-4组1年复发率差异无统计学意义(P=0.37),5×10-3~1×10-4组和>5×10-3组1年复发率差异有统计学意义(P=0.02)。结论 应用FCM动态检测MRD对及时预测复发、指导治疗有重要的临床意义。  相似文献   

2.
 目的 观察前列腺凋亡反应因子4(Par-4)、WT1基因在急性白血病(AL)及非白血病患者骨髓细胞中的表达情况,探讨Par-4、WT1基因表达水平与完全缓解(CR)率的关系。方法 采用荧光定量RT-PCR方法检测78例AL患者及23例非白血病患者骨髓细胞中Par-4、WT1 mRNA的表达。结果 Par-4基因在78例AL患者与23例非白血病患者骨髓细胞中均有表达,在AL患者表达量明显下降(9.35×10-4±8.4×10-5)(P<0.05)。在缓解组表达增强(1.26×10-3±1.1×10-4),与初治组和复发组间差异有统计学意义,但仍低于对照组(3.25×10-3±2.9×10-4)。初治组和复发组间表达差异无统计学意义。Par-4基因表达水平与CR率无明显关系(P>0.05)。WT1基因在AL患者骨髓细胞中高表达(2.98×10-3±2.1×10-4),对照组WT1基因低表达(7.25×10-5±6.7×10-6)(P<0.05)。在缓解组WT1基因表达下降(6.86×10-4±5.2×10-5),与初治组和复发组间差异有统计学意义,但仍高于 对照组。初治组和复发组间表达差异无统计学意义。不同WT1基因表达水平与CR率 间差异有统计学意义(P<0.05)。结论 采用荧光定量RT-PCR的方法证实Par-4基因在AL低表达,而WT1基因高表达,二者呈相反的表达模式。Par-4基因表达水平与CR率无明显关系。  相似文献   

3.
 目的 探讨流式细胞术检测急性髓细胞性白血病(AML)微小残留病(MRD)的临床意义。方法 对21例生存24~128个月成年人AML完全缓解(CR)患者,采用双色直接免疫荧光标记及多参数流式细胞术每隔3~12个月检测一次外周血中MRD,同时检测骨髓细胞形态的变化。结果 21例动态检测MRD水平>10-4患者复发率为80.0 %,MRD水平≤10-4患者复发率为18.1 %。21例随访24 ~ 128个月,复发10例,其中有3例先髓外复发,未复发有11例。10例MRD水平>10-4患者24个月EFS率为30.0 %;11例MRD水平≤10-4患者为90.9 %。MRD水平≤10-4患者中复发的2例,分别在MRD水平升为10-2后3个月、7个月时出现骨髓复发。结论 MRD水平为10-3或以上的患者预后较差,易复发。MRD水平长时间波动在10-3~10-4间,即使骨髓无复发,也要警惕髓外复发。MRD水平≤10-4者生存期长,预后较好。但在生存期超过5年停化疗后,仍应动态监测MRD水平,尤其当MRD水平升至10-2水平时应警防复发,甚至考虑采用干预治疗。  相似文献   

4.
 【摘要】 目的 探讨急性白血病(AL)患者骨髓细胞中间隙连接蛋白43(Cx43)、P-糖蛋白(P-gp)及环氧合酶2(COX-2)基因表达水平及其与AL病程、预后和耐药的关系。方法 77例不同病期AL患者,其中初治36例,完全缓解20例,复发20例,同时以20例异体造血干细胞移植供体及非血液系统恶性病患者为对照。采用SYBR Green实时定量反转录聚合酶链反应(SYBR-RT-PCR)技术,检测骨髓单个核细胞中Cx43、P-gp、COX-2 mRNA的表达,并对37例初治患者进行动态随访。结果 AL初治组Cx43、P-gp、COX-2 mRNA的表达分别为0.52±0.57、1.42±1.06、1.14±0.95,复发组分别为0.20±0.40、2.29±1.11、1.69±0.81,完全缓解组分别为0.95±0.37、0.93±0.73、0.79±0.58,对照组分别为1.16±0.67、0.86±0.63、0.61±0.57。初治、复发AL患者Cx43 mRNA表达水平较对照组及完全缓解组低,差异均有统计学意义(初治组分别P=0.001、0.005;复发组均P<0.001);完全缓解组Cx43 mRNA表水平与对照组相比,差异无统计学意义(P=0.185)。AL患者骨髓细胞液中Cx43 mRNA与P-gp和COX-2 mRNA表达呈负相关,且初治组、完全缓解组及复发组表达均呈负相关(与P-gp r值分别为-0.471、-0.362、-0.526;与COX-2 r值分别为-0.479、-0.344、-0.471)。36例AL初治患者随访4个月,死亡8例,生存28例,死亡患者Cx43 mRNA表达低于生存患者,差异有统计学意义(t=2.16,P=0.042)。结论 初治、复发难治AL患者骨髓中Cx43 mRNA的表达下调,同时多药耐药基因P-gp、COX-2 mRNA的表达上调;Cx43过度表达是预后良好因素,Cx43与AL的疗效、预后及化疗耐药密切相关。  相似文献   

5.
目的 探讨流式细胞术(FCM)联合实时荧光定量聚合酶链反应(RQ-PCR)动态检测急性髓系白血病(AML)患者微小残留病(MRD)和WT1基因表达水平的临床意义.方法 采用FCM联合RQ-PCR检测42例AML住院患者(除外M3)化疗前后349份骨髓标本的MRD值及WT1基因表达量.结果 化疗前AML患者的WT1基因表达水平与疗效无关(x2=0.166 3,P>0.5),首次诱导化疗后形态学完全缓解(CR)患者34例,其中MRD高水平11例,复发率达63.6 %(7/11),低水平23例,复发率21.7%(5/23),两组之间复发率差异有统计学意义(x2=5.729,P< 0.025).WT1基因高水平表达8例,复发率达87.5 %(7/8),低水平26例,复发率23.1%(6/26),两组之间复发率差异有统计学意义(x2=10.749,P<0.005).WT1基因的表达水平在CR后下降(t=4.669,P<0.001).CR后WT1与MRD均为低水平表达者的复发率[15.0%(3/20)]明显低于其中有一项为高水平表达者的复发率[64.3%(9/14)],两组之间差异有统计学意义(P<0.05).且CR后WT1基因及MRD表达量呈正相关(r=0.835,P< 0.001).结论 FCM联合RQ-PCR动态检测AML患者的MRD及WT1基因的表达水平可以作为AML患者MRD的监测指标,同时提高了MRD检测的阳性率,为临床开展个体化治疗及分层治疗提供一定的实验室依据.  相似文献   

6.
 目的 观察FLAG方案在成年人复发难治性急性淋巴细胞白血病(ALL)诱导化疗中的疗效及安全性。方法 对2008年1月至2012年1月收治的复发难治性ALL患者(治疗组)20例,采用FLAG方案补救化疗;选择20例2002年1月至2008年1月住院的复发难治性ALL患者作为对照组,采用首次诱导方案和去甲氧柔红霉素(IDA)联合依托泊苷及大剂量甲基氢化泼尼松方案,比较两组的疗效及不良反应,应用流式细胞术(FCM)以白血病细胞特异分化抗原为标志监测两组微小残留病(MRD),并与传统骨髓形态学结果进行比较。结果 治疗组和对照组血液学不良反应相似(P=0.548),治疗组其他非血液系统不良反应包括肝损伤(4/20)、心脏毒性(1/20),较对照组(9/20 和4/20)轻;大多数不良反应均可耐受。治疗组CR 8例(40.0 %),CR患者平均无病生存期和总生存期分别为6个月(4~30个月)和11个月(9~30个月);对照组CR 7例(35.0 %),CR患者平均无病生存期和总生存期分别为4个月(3~30个月)和9个月(9~30个月),两组总生存期差异无统计学意义。治疗组早期复发率[5.0 %(1/20)]和髓外复发率(0)较对照组[20.0 %(4/20)和10.0 %(2/20)]低。结论 FLAG方案治疗成年人复发难治性ALL不良反应可耐受,为患者选择同种异基因移植争取了时间。  相似文献   

7.
 【摘要】目的 探讨流式细胞术(FCM)检测儿童急性淋巴细胞白血病ALL-B细胞系患儿骨髓微小残留病(MRD)的临床意义。方法 以多种四色荧光标记抗原采用FCM检测ALL-B残留肿瘤细胞对52例ALL-B初诊患儿骨髓细胞进行有效免疫表型组合,并用这些免疫表型组合对ALL-B患儿不同治疗时期的骨髓标本进行MRD监测。结果 52例ALL-B患儿诱导化疗33天,3个月,6个月分别行BM 及MRD监测。并进行长期随访。按照疾病危险度分组,标危组(SR)21例,中危组(IR)23例,高危组(HR)8例,化疗6个月时,MRD阳性数:SR组:21例阳性数4例(19%),IR组:23例阳性数8例(34%),HR组:8例阳性数5例(62%),B-All 52例9例复发,其中SR 21例 2例复发,IR 23例 4例复发 HR 8例 3例复发。结论MRD水平与疾病复发之间存在一定的关系,是具有重要指导意义的疾病预后因素。应用FCM技术对儿童B-ALL进行动态定时监测MRD,对实现白血病治疗个体化早期预测复发,选择合适的治疗方法如不同强度的化疗及骨髓移植具有重要的临床意义。 【关键词】:急性; B-ALL, 流式细胞仪,肿瘤 残留; 复发; 儿童  相似文献   

8.
目的 探讨WT 1基因表达水平与急性白血病 (AL)预后的关系及在微小残留病 (MRD )检测中的意义。方法 采用荧光定量RT PCR法 (FQ RT PCR ) ,测定 40例不同类型及处于不同疾病阶段 (2 6例初治、5例复发、9例CR >3年 )的AL患者WT1基因的表达。结果 对照组WT1基因均为阴性。 40例AL患者中有 2 6例WT 1基因表达阳性 ,阳性组与阴性组CR率分别为 3 4.6%和 78.5 % (P <0 .0 5 )。其中初治、复发与CR >3年的患者 ,WT 1阳性基因拷贝数的平均值分别为 4.14× 10 3 拷贝 /ml、8.5 8× 10 3 拷贝 /ml和 7.87× 10 1拷贝 /ml。CR后WT 1基因表达水平明显下降 ,复发后又显著升高。结论 FQ RT PCR实验方法客观准确 ,WT1基因的表达水平与AL患者的化疗效果及预后密切相关 ,可以作为检测MRD的标志  相似文献   

9.
目的探讨SHP-1和JAK1 mRNA在急性白血病(AL)患者的表达及其与AL复发及初次诱导缓解化疗疗效的关系。方法采用半定量反转录-聚合酶链反应(RT—PCR)的方法检测93例AL患者骨髓单个核细胞中SHP-1和JAK1 mRNA的表达,20例健康志愿者为健康对照。结果初治AL患者SHP-1 mRNA表达水平较健康对照组明显降低(P=0.000),治疗完全缓解(CR)后表达增高(P=0.032),复发时SHP-1 mRNA水平降低(P=0.015);初治AL患者JAK1 mRNA表达水平较NC组略增高,但差异无统计学意义(P=0.051),复发AL患者JAK1 mRNA表达水平较NC组增高,有统计学意义(P=0.047);初治AL患者SHP-1 mRNA阳性组的诱导化疗CR率为88.89%,阴性患者组CR率为60.38%,差异有统计学意义(P=0.018);SHP-1与JAK1 mRNA表达呈负相关(P=0.048)。结论AL患者中SHP-1 mRNA表达降低或缺如,SHP-1 mRNA阳性表达是初治AL患者预后良好的因素,并可作为判断疾病进展的预测指标。AL细胞中JAK1 mRNA丰度可能增高。  相似文献   

10.
目的探讨应用流式细胞术(FCM)检测急性淋巴细胞白血病(ALL)微小残留病(MRD)的临床意义。方法初发ALL患者48例按疾病危险度分为低危组、中危组及高危组。于诱导缓解第33天、3个月、6个月时检测骨髓MRD,进行长期随访。结果诱导缓解第33天和3个月时低危组、中危组及高危组患者的MRD阳性率差异有统计学意义(P=0.0199、P=0.0007)。MRD阴性患者第33天时的复发率为4.0%(1/25),3个月时为11.4%(4/35),两者差异有统计学意义(P=0.0023)。复发前每例患者均可观察到MRD水平呈逐渐升高的趋势。结论MRD水平与ALL的预后及复发关系密切,在治疗及随访过程中密切监测MRD水平可以为临床更加准确地评估早期治疗反应、调整危险度分组及预测复发提供依据。  相似文献   

11.
Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant‐related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T‐cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High‐dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first‐line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high‐risk patients.  相似文献   

12.
Reactivation of latent herpesviruses results in outcomes ranging from asymptomatic shedding of viruses to severe diseases, depending on the immunological competence of the host. Severe and prolonged suppression of cellular and humoral immunity after hematopoietic stem cell transplantation is accompanied by a high incidence of symptomatic recurrent herpesvirus infections. Subclinical reactivation also occurs more frequently than previously expected in transplant recipients. An increasing viral load in the blood detected by an antigenemia assay or PCR and viral shedding in regional fluids have a predictive value for subsequent diseases. Monitoring of viral DNA in the peripheral blood after allogeneic bone marrow transplantation (allo-BMT) reveals unique temporal profiles of detection for each herpesvirus. Recent studies demonstrate that recovery of CD4+ T cells is enhanced within one month after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) compared to allo-BMT. To clarify whether this immunological advantage could affect the reactivation of human herpesvirus (HHV), we monitored the emergence of viral DNA by a nested-double polymerase chain reaction in peripheral blood leukocytes. Detection rates of HHV-6 DNAs which peak at 3-4 weeks post-transplant, were significantly reduced after allo-PBSCT compared to allo-BMT, while those of other herpesviruses which tend to be reactivated later than this period (Epstein-Barr virus and cytomegalovirus) were similar between the two types of transplants. Detection of HHV-6 DNA within the first month after the transplant was associated with delayed platelet engraftment. These results underscore the important role of CD4+ T reconstitution in inhibiting virus reactivation post-transplant.  相似文献   

13.
Previously, we had reviewed 43 cases of invasive cancers, adenosquamous cell carcinoma and adenocarcinoma for HPV type infections. With the same cases we extended the investigation to cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. Results show that the prevalence of CMV and HSV infections from these cases of cervical carcinoma was 67 and 76%, respectively, by polymerase chain reaction. The results of the analysis of the association of HPV, CMV and HSV with various clinical characteristics of cervical cancer patients indicated that the correlation between HSV infections and clinical stages of squamous carcinoma was marginally significant (P=0.068). HSV infections seemed to have a higher association with cell keratinization pattern as compared with the other two viral infections.  相似文献   

14.
目的 观察膦甲酸钠用于异基因造血干细胞移植(allo-HSCT)预防及抢先治疗巨细胞病毒(CMV)感染的疗效及安全性.方法 回顾性分析2014年10月至2016年12月96例接受allo-HSCT患者临床资料.采用实时荧光定量聚合酶链反应(RQ-PCR)监测患者血浆巨细胞病毒(CMV)-DNA情况至移植后6个月,预防及抢先治疗分别采用膦甲酸钠每天60 mg/kg和每天120 mg/kg.观察CMV血症、CMV病发生情况,分析CMV感染的影响因素,分析膦甲酸钠治疗效果和安全性,评估患者生存情况.结果96例患者中42例(43.8%)移植后发生CMV感染,中位感染时间42 d.膦甲酸钠治疗的42例CMV感染患者中,疗效显著36例(85.7%),进展为CMV病6例(14.3%),其中CMV转阴5例,因CMV间质性肺炎死亡1例.半相合移植及Ⅱ~Ⅳ度移植物抗宿主病(GVHD)患者CMV血症发病率升高(χ2=3.834,P<0.05;χ2=16.807,P<0.001).膦甲酸钠不良反应轻微,无明显中性粒细胞减少.发生CMV血症42例中,死亡12例(28.6%),未发生CMV血症54例中,死亡6例(11.1%),两组总生存率差异无统计学意义(χ2=3.546,P=0.06).结论 应用膦甲酸钠对allo-HSCT患者预防及抢先治疗CMV感染的疗效确切,耐受性良好,尤其适用于造血未完全恢复的患者.  相似文献   

15.
BACKGROUND: The association between oral squamous cell carcinoma (OSCC) and viral and chemical factors is uncertain. Therefore the correlation of viral and chemical factors with oral cancer in Taiwan was investigated. METHODS: Thirty-seven paraffin-embedded oral cancer biopsies and 36 normal oral tissue specimens were examined by the polymerase chain reaction method for six viruses: HPV, CMV, EBV, HSV-1, HSV-2 and HHV-8. To elucidate the role of arecoline in the oncogenesis of oral cancer, human buccal fibroblasts, oral submucosal fibroblasts and three cancer cell lines KB, GNM and TSCCa were used for MTT cytotoxity assay and flow cytometry DNA content analysis. RESULTS: Two (5.4%) HSV-1-positive and four (10.8%) HPV-positive cases were recognized in oral cancer biopsies. Among the four HPV-positive tissues, two were further typed as HPV-16, one was identified as HPV-18- and HSV-1-positive; and one contained both HPV-16 and HPV-18. One sample presented HSV-1 only. Arecoline, at a concentration lower than 0.8 micro g/ml, increased cell growth (all cell types); at higher concentrations (25-400 micro g/ml) it was cytotoxic. The cell cycle was demonstrated to be altered either by low or high concentrations of arecoline treatment, depending on the cells treated. CONCLUSIONS: The data demonstrated that HPV, HSV-1 and betel quid chewing were significantly associated with OSCC, but HSV-2, CMV, EBV and HHV-8 were not. We suggest that the most determinative factor for oral cancer may be chemical in nature rather than viral infection.  相似文献   

16.
We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.  相似文献   

17.
We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.  相似文献   

18.
Antibody persistence several months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in allogeneic stem cell transplantation recipients remains largely unknown. We sequentially evaluated the humoral response to two doses of mRNA vaccines in 128 adult recipients and identified the risk factors involved in a poor response. The median interval between stem cell transplantation and vaccination was 2.7 years. The SARS-CoV-2 S1 Ab became positive after the second vaccination dose in 87.6% of the recipients, and the median titer was 1235.4 arbitrary units (AU)/ml. In patients on corticosteroid treatment, the corticosteroid dose inversely correlated with Ab titer. Multivariate analysis identified risk factors for poor peak response such as an interval from stem cell transplantation ≤1 year, history of clinically significant CMV infection, and use of >5 mg/day prednisolone at vaccination. Six months after vaccination, the median titer decreased to 185.15 AU/ml, and use of >5 mg/day prednisolone at vaccination was significantly associated with a poor response. These results indicate that early vaccination after stem cell transplantation (<12 months) and CMV infection are risk factors for poor peak response, while steroid use is important for a peak as well as a persistent response. In conclusion, although humoral response is observed in many stem cell transplantation recipients after two doses of vaccination, Ab titers diminish with time, and factors associated with persistence and a peak immunity should be considered separately.  相似文献   

19.
Aim of the study was to correlate the clinical outcome of eighteen patients who have undergone an allogeneic stem cell transplant (SCT) with the concentration in the peripheral blood (PB) of lymphocyte subpopulations evaluated at 1 year from transplant. The occurrence of acute GVHD and CMV infection correlated with the concentration of Tregs in the PB; CMV infection also correlated with the content of NK cells. The obtained results document that the concentration of Tregs in the PB after an allogeneic SCT may protect from GVHD and from CMV infection; the potential anti-viral role of NK cells is confirmed.  相似文献   

20.
目的:分析儿童异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后患者巨细胞病毒(cytomegalovirus,CMV)感染的发生率及其危险因素,为 CMV 感染的监测及治疗提供参考。方法:通过回顾性分析 2018年01月至 2020 年01月在郑州大学附属儿童医院血液肿瘤科、广州市妇女儿童医疗中心血液肿瘤科行异基因造血干细胞移植患者81例,应用χ2 检验及 Logistics 回归模型,分析 CMV 感染的发生率及其发生的危险因素。结果:81例患者中49例发生 CMV 感染,累计发生率为 60.4%,首次发生CMV感染的时间为移植后 37天(13~135天),所有患者经抗病毒后转为阴性,转阴中位时间为14天(7~51天)。单因素分析提示,CMV感染的发生与性别、疾病类型、供体来源、Ⅰ-Ⅱ度急性移植物抗宿主病(acute graft versus host disease,aGVHD)无明显相关性(P>0.05),与Ⅲ-Ⅳ度aGVHD的发生呈明显相关性(P<0.05);多因素分析提示aGVHD的发生是CMV感染的危险因素。结论:Allo-HSCT后aGVHD的发生增加了CMV感染的发生率,是CMV感染的危险因素。  相似文献   

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