骨髓增生异常综合征的免疫表型特征分析

 【摘要】　目的　评价免疫表型在骨髓增生异常综合征（MDS）诊断中的价值。方法　采用流式细胞术对27例MDS患者的骨髓细胞进行免疫表型检测。结果　随着MDS疾病的进展,CD+34细胞比例逐渐升高,分别为：难治性贫血／环形铁粒幼细胞性难治性贫血（RA／RAS）7.43 %,难治性贫血伴原始细胞增多（RAEB）36.81 %,难治性贫血伴原始细胞增多转化型（RAEB-T）56.45 %,3组差异有统计学意义（F＝51.197,P＝0.000）,且各组间差异均有统计学意义（P＜0.05）;髓系抗原CD33、CD13、HLA-DR表达逐渐增高,CD14、CD15抗原表达随着疾病的进展逐渐降低,3组间差异有统计学意义（P＜0.05）;B淋巴细胞表面抗原CD19、CD10的表达随着疾病进展而降低;T淋巴细胞表面抗原CD7表达随着疾病进展而增高,分别为RA／RAS 2.63 %、RAEB 10.79 % 和RAEB-T 11.00 %,3组间差异有统计学意义（F＝10.439,P＝0.001）,其中RA／RAS组与RAEB组、RAEB-T组之间差异有统计学意义（P＝0.000,P＝0.001）。结论　检测MDS患者骨髓细胞的免疫表型有助于MDS的诊断、分型和判断预后,从而为治疗提供依据。     

骨髓增生异常综合征的免疫表型特征分析

Objective To evaluate the value of immunophenotype in diagnosis of myelodysplastic syndrome (MDS).Methods The immunophenotype of bone marrow cells in 27 patients with MDS were detected by monoclonal antibody by flow cytometry.Results As the progression of the disease,CD34 positive cells gradually increased:refractory anemia/ring sideroblasts refractory anemia (RA/ AS) 7.43 %,refractory anemia with excess of blasts (RAEB) 36.81%,refractory anemia with excess of blasts transformed (RAEB-T)56.45 %,and the differences were statistically significant (P ＜0.05); the expressions of CD33+,CD13 and HLA-DR increased gradually,the expressions of CD14 and CD15 antigens gradually decreased,the difference of three groups was statistically significant (P ＜0.05),the differences between RA/RAS and RAEB-T,RAEB and RAEB-T were statistically significant (P ＜0.05); the expression of CD19 and CD10 decreased and the expression of CD7 increased (RA/RAS 2.63 %,RAEB 10.79 % and RAEB-T 11.00 %) with the progression of the disease,the difference of three groups was statistically significant (F =10.439,P ＜0.05),the differences between RA/RAS and RAEB,RA/RAS and RAEB-T were statistically significant (P ＜0.05).Conclusion The detection of immunophenotype of bone marrow cella in patients with MDS contributes to the diagnosis,classification and prognosis of MDS.     

骨髓增生异常综合征的免疫表型特征分析

Objective To evaluate the value of immunophenotype in diagnosis of myelodysplastic syndrome (MDS).Methods The immunophenotype of bone marrow cells in 27 patients with MDS were detected by monoclonal antibody by flow cytometry.Results As the progression of the disease,CD34 positive cells gradually increased:refractory anemia/ring sideroblasts refractory anemia (RA/ AS) 7.43 %,refractory anemia with excess of blasts (RAEB) 36.81%,refractory anemia with excess of blasts transformed (RAEB-T)56.45 %,and the differences were statistically significant (P ＜0.05); the expressions of CD33+,CD13 and HLA-DR increased gradually,the expressions of CD14 and CD15 antigens gradually decreased,the difference of three groups was statistically significant (P ＜0.05),the differences between RA/RAS and RAEB-T,RAEB and RAEB-T were statistically significant (P ＜0.05); the expression of CD19 and CD10 decreased and the expression of CD7 increased (RA/RAS 2.63 %,RAEB 10.79 % and RAEB-T 11.00 %) with the progression of the disease,the difference of three groups was statistically significant (F =10.439,P ＜0.05),the differences between RA/RAS and RAEB,RA/RAS and RAEB-T were statistically significant (P ＜0.05).Conclusion The detection of immunophenotype of bone marrow cella in patients with MDS contributes to the diagnosis,classification and prognosis of MDS.     

骨髓增生异常综合征免疫表型特征及其临床意义

 骨髓增生异常综合征（MDS）患者骨髓细胞免疫表型在整个疾病过程中呈现出紊乱及异常表达,其中一些改变对其诊断、分型、预后和治疗等方面有一定的价值。就此方面的进展作一综述。     

骨髓增生异常综合征免疫表型的研究

目的：评价免疫表型测定在骨髓增生异常综合征(MDS)诊断及分型中的价值。方法：应用单克隆抗体方法对55例MDS患者进行免疫表型检测。结果：MDS患者髓系抗原表达明显增高,FAB亚型的抗原表达呈现规律性改变,随着RA向RAEB／RAEB-t转化,较早期的髓系抗原(CD33)逐渐增加,较成熟的CD15抗原和T-淋巴细胞抗原逐渐减少;同时在RAEB/RAEB—t阶段CD34^ 细胞数明显增高;较早期的骨髓细胞表面抗原(CD38、HLA-DR)在MDS表达明显增加。结论：免疫表型的检测对MDS更精确的诊断和分型有重要意义。     

流式细胞学评分系统的建立及其在骨髓增生异常综合征诊断中的应用

 目的　建立适用于中国人群的MDS诊断流式细胞学评分系统,以提高MDS早期诊断的准确性。方法　运用多色流式细胞术检测确诊MDS组和对照组CD+34细胞和各分化阶段细胞免疫表型的异常,建立MDS诊断的流式细胞学评分系统;应用该评分系统对37例临床疑似MDS患者进行评分。结果　筛选出12个对MDS诊断有贡献的干细胞或分化阶段细胞抗原表达异常作为MDS流式细胞学诊断的积分指标,根据其在MDS中出现的特异性分别给予1分和0.5分,建立了MDS诊断的流式细胞学评分系统;37例试验组中确诊为MDS的患者评分均＞2分,确诊为非MDS的患者评分均＜5分,当以积3分为截断值时,诊断MDS的敏感度和特异度可分别达到94.1%和80.1%。结论　建立流式细胞学评分系统能有效地辅助MDS的早期诊断和准确诊断。     

维吾尔族和汉族骨髓增生异常综合征患者细胞形态学及免疫表型的对比分析

 【摘要】　目的　探讨新疆地区维吾尔族和汉族骨髓增生异常综合征（MDS）患者的细胞形态学和免疫表型特征。方法　对已确诊的67例MDS患者骨髓涂片进行系统观察分型,记录各系病态造血细胞,并进行流式细胞术（FCM）免疫表型检测。结果　67例MDS患者骨髓细胞的粒、红、巨核三系有不同程度的病态造血,依次为粒系[52例（77.6 %）]、巨核系[44例（65.7 %）]、红系[36例（53.7 %）],维吾尔族和汉族患者骨髓三系中出现病态造血表现的比例相近,两组差异无统计学意义（χ2值分别为1.02、0.30、0.02,均P＞0.05）。67例骨髓细胞病态造血改变类型的发生率依次为单圆核巨核细胞 [36例（53.7 %）]、假Pelger核异常粒细胞 [36例（53.7 %）]、红系巨幼样变[33例（49.3 %）]、粒细胞颗粒减少或缺失[27例（40.3 %）]等,维吾尔族和汉族患者发生率相似。67例MDS患者FCM免疫表型检测结果显示,随着MDS的难治性贫血／难治性贫血伴环形铁粒幼细胞向难治性贫血伴原始细胞过多（RAEB）／转化中的RAEB的进展变化,较成熟的CD15表达率逐渐降低,而较早期的CD34、CD117表达率逐渐升高（χ2值分别为6.23、12.06,8.95、7.37,8.95、8.08,均P＜0.05）,维吾尔族和汉族患者差异无统计学意义（χ2值分别为0.715、0.024、0.146,均P＞0.05）;同时维吾尔族患者CD56表达增高,汉族MDS患者HLA-DR增高,两组比较差异有统计学意义（χ2值分别为3.91、3.90,均P＜0.05）。结论　维吾尔族和汉族MDS患者骨髓细胞形态学病态造血改变相同,多数MDS有两系以上的病态造血。维吾尔族和汉族MDS患者免疫表型抗原表达部分不同,免疫表型的检测对MDS的诊断、分型及预后具有重要意义。     

骨髓增生异常综合征红细胞免疫功能变化及其意义

对２８例骨髓增生异常综合征（ＭＤＳ）患者红细胞免疫功能进行研究，结果表明：红细胞Ｃ３ｄ受体花环率明显降低，红细胞免疫粘抑制因子活性升高，而增强因子则下降，上述指标与正常组比较，差异极显著（Ｐ〈０．０１），同时发现红细胞循环免疫复合物花环率正常，提示ＭＤＳ患者红细胞免疫功能紊乱，并非由于红细胞粘连过多免疫复合物所致，而是由于红细胞膜表面Ｃ３ｂ受体数量减低及免疫调控失效所致，红细胞免疫功能下可能是患者     

骨髓增生异常综合征红细胞免疫功能变化及其意义

对２８例骨髓增生异常综合征（ＭＤＳ）患者红细胞免疫功能进行研究，结果表明，红细胞Ｃ３ｂ受体花环率明显降低，红细胞免疫粘附抑制因子活性升高，而增强因子则下降，上述指标与正常组比较，差异极显著（Ｐ＜０．０１）。同时发现红细胞循环免疫复合物花环率正常。提示ＭＤＳ患者红细胞免疫功能紊乱，并非由于红细胞粘附过多免疫复合物所致，而是由于红细胞膜表面Ｃ３ｂ受体数量减低及免疫调控失调所致，红细胞免疫功能低下可能是患者易感染的因素之一。     

骨髓增生异常综合征原癌基因Bmi-1表达的检测

目的：检测原癌基因Bmil在骨髓增生异常综合征（myelodysplastic syndrome,MDS）患者中的表达,探讨其在MDS中的临床意义。方法：选择201009—04—2013—01-10在泰山医学院附属医院就诊的69例MDS患者及30例非恶性血液病患者骨髓标本,应用SYBRGreen相对定量RT—PCR方法,进行Bmi-1基因的检测。结果：Bmi—1基因在非恶性血液病患者中无表达。在69倒MDS患者中均有表达（2．28±0．84）,且表达水平明显高于非恶性血液病患者组,t=14．787,P〈0．001。其中,RA组明显高于对照组（P〈0．001）,RAEB组明显高于RA组,P=0．001。Bmil基因高表达组CD34＋CD38-CD123＋／CD34＋为（10．77±5．51）％,低表达组为（4．65±3．36）％,差异有统计学意义,t=5．741,P=0．037。Bmi-1基因高表达组,骨髓原始细胞≥5％的病例数（17例）高于低表达组（14例）,χ2=7．057,P=0．012;Bmi1基因高表达组具有预后不良染色体核型的有6例,Bmi-1低表达组仅有3例,但两组间差异无统计学意义,χ2=2．794,P=0．144。结论：MDS患者的骨髓单个核细胞中均存在Bmi-1基因不同程度的表达升高,为MDS的诊断及预后的评价提供了新的方向。     

Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome

BACKGROUND:

Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low‐risk patients remains controversial.

METHODS:

The authors analyzed the incidence and prognostic significance of thrombocytopenia at diagnosis in 2565 de novo MDS patients included in the Spanish MDS Registry.

RESULTS:

Thrombocytopenia (platelet count <100 × 10⁹/L) was identified in 842 patients (32.8%). Severe thrombocytopenia (platelet count <30 × 10⁹/L) was observed in 7.1% of patients and was significantly associated with a higher‐risk World Health Organization subtype (P = .026) and intermediate‐2/high‐risk International Prognostic Scoring System (IPSS) score (P = .046). Severe thrombocytopenia was the most important prognostic factor and had negative effects on the low/intermediate‐1 risk group. Median overall survival of patients with a platelet count <30 and ≥30 × 10⁹/L was 16 months and 71 months, respectively (hazard ratio, 4.66; 95% confidence interval, 2.74‐7.90; P < .0001). The negative effect of severe thrombocytopenia in low/intermediate‐1 risk patients was caused by increased risk of bleeding.

CONCLUSIONS:

MDS patients with low/intermediate‐1 IPSS risk score and severe thrombocytopenia should no longer be regarded as low risk, and must be considered for disease‐altering approaches at diagnosis. Cancer 2011;. © 2011 American Cancer Society.     

Platelet response during the second cycle of decitabine treatment predicts response and survival for myelodysplastic syndrome patients

Despite the efficacy of decitabine to myelodysplastic syndrome (MDS), there is a wide range of responses, and no definite predictive marker has been identified. This study aimed to describe the efficacy of decitabine and to identify potential predictors of response and survival in patients with MDS. We retrospectively analyzed clinical data of MDS patients at Samsung Medical Center between August 2008 and August 2011. The response assessment was conducted using the International Working Group (IWG) response criteria for MDS. We analyzed 101 MDS patients (total 613 cycles) who received decitabine for a median of four cycles. The overall response was 52.5% (n = 53/101). The median time to any response was two cycles with the median overall survival of 16.7 months. Patients who showed hematologic improvement had significantly longer survival than those who did not (9.8 vs. 22.9 months, p = 0.004). The difference in OS was evident in the Intermediate-2/High risk group (p = 0.002) but not in the Intermediate-1 risk group (p = 0.145). Multivariate analysis confirmed that platelet response (no platelet transfusions for at least 3 days) during the second cycle of treatment was an independent predictor for response, OS and Leukemia free survival. Based on the results of this study, for patients with hematological improvement, recovery of platelet count by the second cycle of therapy can be used as an early predictive marker of improved survival and an increased response rate.     

低增生性骨髓增生异常综合征临床分析

 目的 探讨低增生性骨髓增生异常综合征（hypo-MDS）的临床特征、实验室指标及治疗。方法 对8例hypo-MDS患者的临床特点、骨髓涂片及骨髓活检结果进行分析，用流式细胞仪测定T细胞亚群，采取个体化治疗方案，随访观察疗效。结果 8例患者均有2个以上部位骨髓增生低下、骨髓低细胞容积和不同程度病态造血。T细胞亚群分析结果显示5例有T细胞数目、CD+4／CD+8比例异常。治疗后2例基本缓解，3例部分缓解，2例进步，1例无效。结论 hypo-MDS以骨髓低细胞容积和病态造血为共同特征，表现为细胞免疫异常，采取个体化治疗原则可延长患者生存期。     

Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade glioma

In patients with recurrent malignant glioma, treatment-related myelodysplastic syndrome (t-MDS) and acute leukemia are rare adverse effects because the median survival after relapse is limited. We report a 44-year-old woman with t-MDS (refractory anemia with excess blasts) following treatment of recurrent anaplastic astrocytoma with temozolomide (TMZ). A cytogenetic study showed del (3)(q11.1). MDS was diagnosed 8.4 months after beginning TMZ. The disease rapidly evolved into acute leukemia within 1 month after the onset of MDS, and the patient died 1 month later during induction chemotherapy. The prognosis of t-MDS is generally poor. Considering the increasing use of TMZ, which is regarded as a drug with moderate toxicity, careful follow-up with routine blood testing is vital.     

Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy

BACKGROUND:

The prognosis of patients with myelodysplastic syndrome (MDS) after decitabine failure is not known.

METHODS:

Data from 87 patients with MDS (n = 67) and chronic myelomonocytic leukemia (n = .20) after failure of decitabine regimens were reviewed.

RESULTS:

After a median follow‐up of 21 months from decitabine failure, 13 (15%) patients remained alive; the median survival was 4.3 months, and the estimated 12‐month survival rate was 28%. The estimated 12‐month survival rates were 27%, 33%, and 33%, respectively, for patients with high‐risk, intermediate‐2‐risk, and intermediate‐1‐risk disease (P = .99) by the International Prognostic Scoring System. The estimated 12‐month survival rates were 100%, 54%, 41%, and 18%, respectively, for patients with low‐risk, intermediate‐1‐risk, intermediate‐2‐risk, and high‐risk disease according to The University of Texas M. D. Anderson Cancer Center risk model (P = .01).

CONCLUSIONS:

The outcome of patients after decitabine failure is poor and appears to be predictable after decitabine failure. Cancer 2010. © 2010 American Cancer Society.     

Phase II study of doxercalciferol for the treatment of myelodysplastic syndrome

We conducted a phase II trial of doxercalciferol, a vitamin D₂ analogue, in 15 patients with MDS. Each received doxercalciferol 12.5 µg orally daily for 12 weeks. Nine of 15 patients completed the prescribed course and of these, six had stable disease. No patient had a response (IWG criteria) and overall eight patients experienced progressive disease while on therapy. Two patients with chronic myelomonocytic leukemia (CMML) had a marked rise in monocytes on study. Overall the treatment was well tolerated. One patient was removed from study due to hypercalcemia. We conclude that short-term treatment with doxercalciferol has limited activity in patients with MDS.     

Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy

Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.