t(8;21)急性髓系白血病患者MICM分型及预后的回顾性分析

 目的　分析t(8;21)急性髓系白血病（AML）患者的细胞形态学、免疫表型、遗传学、分子生物学（MICM）分型及临床治疗疗效。方法　运用瑞特染色法、FAB细胞形态分类标准、流式细胞术（FCM）直接免疫荧光标记技术、遗传学染色体吉姆萨显带技术及RT-PCR技术对70例确认有t(8;21)与AML1-ETO融合基因双阳性的AML患者及70例正常染色体核型的AML患者进行分析和比较。结果　70例t(8;21)AML患者中M1 1例,M2 64例,M4 3例,无法分型的急性白血病（AL）2例;免疫表型分析发现CD13、CD33、CD34、CD117高表达,40 %表达CD19,11 %表达CD15,10 %表达CD11b,7 %表达CD7;遗传学显示50 %的t(8;21) AML患者有附加染色体异常,主要为性染色体丢失、9q-及超二倍体;RT-PCR检测AML1-ETO融合基因100 %阳性。CD+19 t(8;21) AML患者完全缓解（CR）率72 %,CD+19伴CD+7 t(8;21)AML患者CR率为0,正常核型CR率31 %。结论　t(8;21) AML患者主要在M2中集中出现,附加染色体异常较多见。CD19表达较高,而CD7表达极低,CD34、CD117高表达,这些抗原的表达可能与核型密切相关。CD+19 是预后良好的指标,但同时出现CD+7,则预后不良。     

伴4号染色体三体异常的t（8；21）急性髓系白血病c-kit基因突变的发生及患者预后

目的：探讨伴有4号染色体三体异常的t（8;21）急性髓系白血病（AML）c-kit基因突变的发生率及患者预后。方法回顾性分析2005年2月至2013年1月145例初治t（8;21）AML患者的实验室及临床资料。所有骨髓样本均采用R显带技术进行核型分析。采用PCR方法检测c-kit基因8号、17号外显子突变情况,并分析患者的临床预后。结果145例t（8;21）AML患者中,12例（8.3%）伴有4号染色体三体异常,其c-kit基因突变发生率为91.7%（11／12）,明显高于其他患者[26.3%（35／133）]（P＜0.01）。生存分析显示,伴有4号染色体三体异常的t（8;21）AML患者的3年总体生存（OS）率及无病生存（DFS）率（15%、0）均低于其他t（8;21）AML患者（56%、51%）（P＜0.01）。同时伴有4号染色体三体及c-kit基因突变的t（8;21） AML患者的OS率及DFS率均较不伴有或不同时伴有4号染色体三体及c-kit基因突变的患者低（均P＜0.05）。结论伴有4号染色体三体异常的t（8;21）AML患者c-kit基因突变发生率高,且预后不佳。4号染色体三体异常或联合c-kit基因突变是影响t（8;21）AML患者生存的主要因素。     

弥漫大B细胞淋巴瘤患者染色体改变及其与生存期的关系

 【摘要】 目的 明确弥漫性大B细胞淋巴瘤患者常见的染色体改变及其与生存期的关系。方法　采用改进的染色体制备方法,对30例经病理活组织检查确诊的弥漫性大B细胞淋巴瘤患者进行染色体分析,并予相应的化疗方案处理,统计各组患者的生存期。结果 28例获得满意的染色体分裂象,其中5例染色体核型正常,8例为多倍体,4例发生t（14;18）（q32;q21）,5例发生t（3;14）（q27;q32）,2例发生t（2;3）（p11;q27）,1例发生t（3;22）（q27;q11）,2例涉及7号染色体与其他染色体间异位,1例涉及17号染色体与其他染色体间异位。染色体核型正常以及发生t（14;18）（q32;q21）和3q+改变的患者,生存期分别为（71.4±2.0）、（67.9±1.6）和（69.1±1.7）个月,较多倍体、7号染色体异常、17号染色体异常患者明显延长（均P＜0.05）。Ⅰ+Ⅱ期患者中,正常染色体核型、t（14;18）（q32;q21）以及3q+患者生存期较发生多倍体改变患者以及7号染色体发生改变患者明显延长（P＜0.05）。Ⅲ+Ⅳ期患者中,发生多倍体改变患者生存期亦较发生t（14;18）（q32;q21）、3q+以及正常染色体核型患者缩短（P＜0.05）。且Ⅰ+Ⅱ期正常染色体核型、t（14;18）（q32;q21）、3q+以及多倍体患者与Ⅲ+Ⅳ期生存期比较,差异均有统计学意义（均P＜0.05）。结论 依据恶性淋巴瘤患者染色体改变及其与恶性淋巴瘤分期等的相关性研究,可以预测淋巴瘤患者的治疗效果、生存期等。     

美国西南肿瘤组/东部肿瘤协作组染色体核型分组法与急性髓系白血病预后关系的研究

 目的　探讨急性髓系白血病（AML）患者染色体核型异常发生率、分布以及美国西南肿瘤组与东部肿瘤协作组（SWOG／ECOG）染色体核型分组法在预后评价中的意义。方法　常规培养83例AML患者的骨髓细胞,吉姆萨显带分析染色体核型。根据SWOG／ECOG核型分类方法对核型进行分组,采用Kaplan-Meier方法观察不同危险组的生存情况。结果　83例AML患者中56例细胞核型检出异常（67.47 %）。AML伴t(15;17)易位与伴t(8;21)易位在异常核型患者中所占比例为53.57 %（30／56）,其余核型分布较分散。随访的74例患者中,42例死亡。预后良好、中等、不良3组生存期比较差异具有统计学意义（P＜0.001）。预后良好组完全缓解率高于预后中等及不良组（P＜0.05）,预后中等组与不良组差异无统计学意义（P＞0.05）。结论　细胞遗传学改变是影响白血病预后的主要因素之一,SWOG／ECOG核型分组能比较客观地反映AML的预后。     

以吡喃阿霉素为基础的联合化疗方案治疗急性髓系白血病的疗效及其预后因素分析

目的:分析采用以吡喃阿霉素(pirarubicin, THP)为基础的联合方案治疗急性髓系白血病(acute myeloid leukemia, AML)患者的完全缓解(complete remission, CR)率、无病生存(disease free survival, DFS)以及总生存(overall survival, OS)情况,探讨不同预后因素对于缓解率及其预后的影响.方法:采用以THP为基础的联合方案诱导治疗初治的原发AML患者29例,计算CR率、DFS期、OS期以及1、2年的DFS率和OS率.根据患者年龄、白细胞计数、FAB分型、染色体核型以及免疫表型进行分组,比较各组之间的CR率、总体有效率[部分缓解(partial remission, PR)+CR]和OS期(率).结果:经1个疗程的TA(THP+阿糖胞苷)方案诱导治疗后,19例(65.5%)患者达到CR,6例(20.7%)患者达到PR,4例(13.8%)患者未缓解(no response, NR),总体有效率(PR+CR)为86.2%.19例CR患者的中位DFS期为22.9(4.0～27.0)个月,1、2年的DFS率均为77.1%.患者的中位OS期为18.6(2.0～28.1)个月,1、2年的OS率分别为58.6%和52.8%.年龄<45岁、白细胞计数<20×109/L、FAB分型为M2、染色体核型为良好和中等组、CD9和CD56阴性者的总体有效率(PR+CR)较高.log-rank单因素分析结果显示,年龄<45岁和FAB分型为M2者的OS期较长.结论:采用TA方案诱导治疗AML具有较好的疗效,不良反应较少.患者年龄、白细胞计数、FAB分型、染色体核型以及CD9、CD56的表达是影响治疗有效率的预后相关因素.     

有助于t(8;21)急性髓细胞白血病的诊断和预后判断的免疫表型特征

 t(8;21)核型急性髓细胞白血病（AML）是临床常见类型白血病,更多见于FAB分型M2型。由于21号染色体上的AML1基因和8号染色体上的ETO基因发生融合,而产生AML1-ETO融合蛋白。t(8;21) AML具有独特的免疫表型,这些独特的免疫表型特征不仅有助于t(8;21) AML的诊断,而且决定了t(8;21) AML的预后     

急性髓系白血病细胞遗传学特征与诱导治疗反应的相关性分析

  目的　探讨急性髓系白血病（AML）细胞遗传学分布特征及其与诱导治疗反应的相关性。方法　对初诊为AML的395例患者的染色体核型进行分析,按照美国国立综合癌症网络（NCCN）白血病指南分为预后良好组、预后中等组和预后不良组。分析各组核型发生比及其1个疗程诱导治疗后的完全缓解（CR）率。结果　预后良好、中等及不良核型分别占50.56 %（180／356）、39.89 %（142／356）、9.55 %（34／356）。预后良好核型t（15;17） 113例中,接受并完成1个疗程诱导治疗的101例患者均达CR。单纯t（8;21）组与合并其他染色体异常的t（8;21）组CR率比较差异有统计学意义[92.00 %（23／25）比 50.00 %（11／22）]（χ2＝10.317,P＝0.001）。正常核型及-Y异常两组核型CR率比较差异无统计学意义[61.90 %（39／63） 比 58.82 %（10／17）]（χ2＝0.054,P＝0.817）。复杂核型中以单体核型最多见,经治疗的10例单体核型患者9例未达缓解。结论　初诊AML患者细胞遗传学分布特点与国际其他中心报道略有差异。AML患者细胞遗传学特征不仅与长期生存相关,而且与诱导治疗后CR率密切相关。     

42例急性非淋白血病的核型研究

本组用G显带法对42例急性非淋白血病(ANLL)核型进行研究。FAB分类:M_228例、M_311例、M_1、M_4、M_6各1例。正常核型16例,占38.1%,异常核型26例,占61.9%,其中t(8:21)7例,占总数16.7%,占M_2的25%;t(15:17)7例,亦占总数16.7%,占M_3的64%;乃外还发现少见核型t(7:11)2例,ph( )2例,3q21断裂2例,各占4.7%;—y6例,其中4例与t(8:21)同时存在。t(8:21)7例中4例有—y;超二倍体7例,多于亚二倍体,以 8 13多见,伴有t(8:21)、t(15:17)各1例。42例中35例经维甲酸(RA)诱导分化(M_3)或化疗(DA,HAT,HOAP)(其它FAB类型),16例完全缓解,总缓解率为45.7%,中位生存期在缓解病例为9~ 月,未缓解病例为3月(P<0.01)。所有缓解病例的核型都在正常核型、t(8:21)、t(15:17)、t(7:11)和—y范围内,而超二倍体、ph( )及3q21断裂核型中无1例达到完全缓解。本组研究除发现数例罕见核型外,显示ANLL核型检查对予后判断有明显价值。     

急性髓细胞性白血病核型与预后相关性分析

 目的　评价染色体核型在急性髓细胞性白血病（AML）预后评估中的意义。方法　对形态学及免疫分型诊断为AML的病例,取骨髓细胞行吉姆萨显带核型检测,进一步诊断、系统化疗,并回顾性分析核型与疗效的关系。结果　62例患者中,36例（58.06 ％）患者出现核型异常,具有t(8;21)、t(15;17)或del(16)的患者的总体完全缓解率（86.96 ％）显著高于其他异常核型 （46.15 %）和正常核型者（65.30 %）。结论　骨髓细胞核型可作为AML预后评估的指标,同时有助于AML的疗效判断及指导治疗。     

附加染色体异常的费城染色体阳性慢性粒细胞白血病患者临床特征及预后分析

目的:探讨附加染色体异常的费城染色体（Ph）阳性慢性粒细胞白血病（CML）患者的临床特征及预后。方法:回顾性分析2009年1月至2019年1月于青岛大学附属医院诊断的351例Ph + CML患者资料,患者均经R显带技术进行骨髓染色体核型分析。总结初诊时附加染色体异常Ph + CML患者临床特征及核型,采用Kaplan-Meier法分析不同核型患者总生存（OS）差异。 结果:351例Ph + CML患者中,32例（9.1%）为变异易位。初诊时附加染色体异常47例,包括慢性期29例、加速期3例和急变期15例,分别占全组慢性期的9.15%（29/317）、加速期的25.00%（3/12）和急变期的68.18%（15/22）,各期附加染色体异常发生率差异有统计学意义（ χ2=50.799, P<0.05）;47例附加染色体异常的Ph + CML患者中,13例为附加3种以上染色体异常的复杂核型,慢性期、加速期、急变期复杂核型比例分别为13.79%（4/29）、33.33%（1/3）、53.33%（8/15）,差异有统计学意义（ χ2=9.26, P<0.05）。慢性期患者中最常见的附加染色体异常为双Ph（48.28%,14/29）、-Y（10.34%,3/29）,急变期患者中最常见的为+8（26.67%,4/15）、双Ph（26.67%,4/15）。Kaplan-Meier生存分析显示,Ph + CML患者中,初诊时附加染色体异常者OS较非异常者差（ χ2=61.138, P<0.05）;初诊时附加染色体异常的Ph + CML患者中,复杂核型者OS较非复杂核型者差（ χ2=4.945, P<0.05）。 结论:附加染色体异常与CML疾病进展密切相关;附加染色体异常的Ph + CML患者的预后较只有Ph易位的患者差。附加染色体越复杂,CML急变的可能性越大,预后也越差;在CML治疗过程中出现附加染色体异常也可能导致急变的进展。     

Response to 5-azacytidine in patients with refractory acute nonlymphocytic leukemia and association with chromosome findings

Fifteen patients with acute nonlymphocytic leukemia (ANLL) who either had a relapse after a previous complete remission (nine patients) or progressive disease after initial induction attempts with combination chemotherapy (six patients) were treated with 5-azacytidine. Five patients (33%) achieved a complete remission (CR); of these, three had a relapse and died 30, 35, and 38 weeks after 5-azacytidine therapy was begun. Two patients are still alive at 39 and 138 weeks. Chromosomes were analyzed at the time of diagnosis; ten patients had a normal karyotype and five had an abnormal karyotype. Three of the five CR patients had an abnormal karyotype initially. Two of these individuals had a translocation of chromosomal material from a No. 8 chromosome to a No. 21 chromosome, t(8;21); this particular translocation has been associated with a better prognosis than have other types of chromosomal abnormalities in patients with ANLL. Even when abnormal chromosomes are present, 5-azacytidine can induce complete remission in patients with previously treated ANLL.     

Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21

Forty-three patients with acute myelogenous leukemia (AML) and a translocation 8;21 were reviewed. The patients' median age was 30 years, and 62% were men. Twenty-three patients (53%) had loss of a sex chromosome and ten (23%) had other chromosomal abnormalities in addition to the 8;21 translocation. Complete remission (CR) with induction chemotherapy was achieved in 40 patients (93%). The median CR duration was 18 months (range, 1 to 137+ months). Median survival time was 17 months (range, 0.5 to 138+ months) with a 3-year survival rate of 31%. Twenty-three patients (53%) relapsed between 1 and 58 months after entering remission with reinduction therapy resulting in 8 CRs (35%). Thirteen characteristics were examined for an effect on survival. The most striking finding was a significant association between elevated absolute granulocyte count and poor survival (P = .002). WBC count greater than 10,000/microL was also associated with shorter survival (P = .05). Patient age, albumin level, and platelet count showed trends for survival association. Although patients with AML and t(8;21) are regarded as a favorable group with respect to survival, we found a subset of patients who do very poorly. Intensive or more investigational approaches in first remission should be considered for these patients.     

急性髓系白血病细胞遗传学特征及不同剂量柔红霉素DA方案化疗效果分析

目的 分析急性髓系白血病(AML)(非M3型)染色体及相关融合基因的遗传学特征,评估其采用不同剂量柔红霉素及标准剂量阿糖胞苷组成的DA方案化疗的预后.方法 收集2013年1月至2015年1月确诊的56例初治AML(非M3型)患者,采用短期培养法处理骨髓样本,用R显带核型分析进行细胞遗传学检测,并应用反转录聚合酶链反应(RT-PCR)和10%聚丙烯酰胺凝胶电泳对标本进行31种融合基因分型检测.接受DA方案诱导治疗时按照不同柔红霉素剂量将患者分为3组(减低剂量组、标准剂量组、大剂量组),观察3组患者治疗后完全缓解(CR)率及生存期,并采用χ2检验分析细胞遗传学和分子生物学异常对3组患者化疗效果及总生存(OS)率的影响.结果 56例患者中染色体核型异常18例(32.1%),其中染色体数目异常6例(10.7%),结构异常16例(28.6%),同时有数目和结构异常4例(7.1%).最常见的结构异常为t(8;21),数目异常为+8、-Y.融合基因检出率为48.2%(27/56),其中AML1-ETO 13例,CBFβ-MYH114例,AML1-MDS13例.融合基因和染色体核型分析使AML患者的遗传学异常检出率提升至62.0%.采用DA方案诱导化疗的总CR率为73.2%,2年OS率为42.9%.标准剂量组中中危患者的化疗缓解率低于低危患者(χ2=8.976,P=0.002);低危患者中减低剂量组与标准剂量组的化疗缓解率差异无统计学意义(P>0.05),但标准剂量组2年OS率有优势(χ2=8.045,P=0.005).结论 成年人AML具有独特的细胞遗传学特征,可辅助指导临床诊断、分型及预后判断.中危患者的预后差于低危患者,低危患者采取减低剂量DA方案也可获得较好的化疗缓解率,但标准剂量DA方案在长期生存方面优势显著.     

Disease features in acute myeloid leukemia with t(8;21)(q22;q22). Influence of age, secondary karyotype abnormalities, CD19 status, and extramedullary leukemia on survival.

Over a period of 14 years, 50 patients (12 children and 38 adults) of whom 46 had acute myeloid leukemia (AML) and 4 had myelodysplastic syndrome characterized by the t(8;21)(q22;q22) translocation were referred to the Royal Marsden Hospital. The clinicopathological features of these cases were analyzed to determine the influence of age, secondary karyotype abnormalities, and expression of the lymphoid marker CD19 on event free survival, and presence of extramedullary leukemia on overall survival. They were treated with a variety of chemotherapy protocols and some had bone marrow transplantation. There appeared to be no difference in survival between children (age <17 years) and adults (age >16 years). Out of the 50 cases, 16 (32%) had the (8;21) translocation alone, 17 (34%) had additional loss of a sex chromosome and the remaining 17 (34%) had other karyotype abnormalities of which deletion or translocation of the long arms of a #9 was most common (observed in 8 of the 17 patients). The karyotype groups had a significant impact on survival, the group with loss of a sex chromosome having a poorer outcome and the group with abnormalities of chromosome 9 having a better outcome. CD19 positivity was seen in 21 of the 33 cases (63%) in whom it was measured compared to 11% observed in controls with AML without a t(8;21). CD19 status did not exert any influence on event free survival. Extramedullary leukemia (EML) occurred in 5 of the 50 cases (10%). In one patient it was observed at diagnosis but in the others it presented concurrent with bone marrow relapse. The overall survival of patients with EML was worse than that of the other patients but did not achieve statistical significance and was probably adversely affected by other factors.     

Cytogenetics and their prognostic value in childhood and adult acute lymphoblastic leukemia (ALL) excluding L3

Cytogenetic analysis was made at diagnosis in 174 cases of ALL (101 children less than 20 years and 73 adults), excluding Burkitt's ALL (L3). In 11 children (11 per cent) insufficient material was obtained. In the remaining 90, 50 (56 per cent) had a normal karyotype, 20 (22 per cent) a hyperdiploid karyotype, five (6 per cent) a hypodiploid karyotype, 12 (13 per cent) had a translocation (including seven cases of t(1;19)) and three had a pseudodiploid karyotype without translocation. Ninety-eight per cent of patients reached complete remission (CR). Median actuarial CR duration was not attained, was 50 months, 13 months and 11 months respectively in patients with hyperdiploid, normal, hypodiploid karyotype and in patients with a translocation, the difference between subgroups being significant. In a Cox model, cytogenetics were the strongest factor predicting CR duration (p = 0.03) followed by leukocytes (p = 0.04), whereas the presence of ‘bulky disease’ had a borderline value (p = 0.077). Of note was that 9/17 (53 per cent) patients with a hypodiploid karyotype or a translocation had no ‘risk factors’ before cytogenetic analysis. In adults, cytogenetic analysis was unsuccessful in 15 (20 per cent) of patients. In the remaining 58 cases, 19 (33 per cent) had a normal karyotype, 15 (26 per cent) had a hyperdiploid, one (2 per cent) had a hypodiploid karyotype, 19 (33 per cent) had a translocation (including 12 t(9;22)), and four (7 per cent) had a pseudodiploid without translocation. 73 per cent patients reached CR. Median actuarial DFS was 12.5 months. No significant differences in CR rate and CR duration were seen between cytogenetic groups, but median CR duration was slightly longer in patients with a normal karyotype (17 months) and shorter in patients with t(9; 22) (8.5 months). Only 3/12 of the latter had major risk factors before cytogenetic analysis. Cytogenetic analysis is important in ALL, especially in patients with otherwise standard risk factors, as it may reveal unexpected translocations or hypodiploidy, which may require a therapeutic reinforcement.     

Cytogenetic and clinical assessment of six patients with erythroleukemia

We report the detailed karyotypic analysis and clinical features of six patients with erythroleukemia (EL). Five of six patients studied displayed substantial numeric and structural chromosome abnormalities. The most common alterations in these patients were monosomy for chromosome 7 and 16. All five patients displaying chromosomal abnormalities presented with 100 percent abnormal metaphases in their bone marrow at the time of initial diagnosis. The remaining patient was studied only during remission and had a normal diploid karyotype in all marrow cells analyzed. No patient in this study had either a Ph1 -chromosome (characteristic of CML), or translocations of chromosome #8-#21 (characteristic of AML-M2). Clinically, all but one patient had a brief history; the exception having had polycythemia rubra vera for 18 years prior to the onset of EL. All patients were treated with current Southwest Oncology Group (SWOG) protocols using cytosine arabinoside and anthracycline combinations. Three of five patients entered complete remission. However, remission durations were short (approximately six months) and median survival just over one year. Cytogenetic analysis of three patients in hematologic remission revealed persistence of chromosomal alterations. It is suggested that such remissions be reclassified as partial rather than complete based upon the cytogenetic information.     

T(1;21;8)(p34;q22;q22): a novel variant of t(8;21) in acute myeloblastic leukemia with maturation

The complex variants of t(8;21) involving chromosomes 8 and 21 as well as another chromosome account for approximately 3% of acute myeloid leukemia patients. We report here a 30-year-old male patient with AML-M2. Fluorescence in situ hybridization analysis using dual-color fluorescence ETO and AML1 probes located at 8q22 and 21q22 respectively showed an AML1/ETO fusion signal on the derivative chromosome 8. Whole chromosome painting probes were used for chromosome 1, 8 and 21 and revealed a three-way translocation (1;21;8)(p34 ~ p35;q22;q22). Involvement of chromosome region 1p34 has never been reported earlier, although region 1p35 as a variant in AML with t(8;21) has been reported with an AML1/ETO fusion signal on the 1p35 rather than der(8). In conclusion, combining conventional karyotype, FISH or RT-PCR analyses are a rational strategy for the identification of the complex variants of t(8;21) translocation which could be critical events responsible for leukemogenesis.     

Prognosis of patients with a second relapse of acute myeloid leukemia.

Recurrence of the disease is the major problem in the treatment of acute myeloid leukemia (AML). The majority of patients who achieve a second remission will ultimately relapse. In this retrospective single-center study, we have analyzed the outcome of patients with a second relapse and tried to define the prognostic factors in intensively treated patients. Of 534 patients with AML, 62 had a second relapse. Thirty-three received further intensive chemotherapy (CT). Eighteen patients (55%) achieved a third complete remission (CR). The early death (ED) rate was only 9%. The overall survival (OS) of treated vs untreated patients was 6.9 vs 1.3 months, respectively (P = 0.01). The major selection criteria for a third CT were a favourable (t(15;17),t(8;21),inv(16)) or normal karyotype, long (>11 months) second CR (P < or = 0.005) and no previous bone marrow transplantation (BMT)(P < 0.01). Favorable or normal karyotype, second CR >11 months, as well as no previous BMT (P < 0.01) were associated with the achievement of a third CR. Favorable (P < 0.005) or normal karyotype (P < 0.01), as well as a second CR >11 months (P < 0.005) were associated with prolonged survival after CT. The median OS for patients receiving CT with favorable or normal cytogenetics, a second CR > 11 months, but no previous BMT was 26.5 months. Five patients with favorable or normal karyotype achieved a fourth or fifth remission. We conclude that intensive CT is associated with a survival benefit and good quality of life if patients are properly selected.