Clinical and prognostic investigations on M2/t(8;21) acute nonlymphocytic leukemia

Summary Clinical and prognostic investigations were conducted in 46 cases of M2/t (8;21) leukemia and 29 cases of M2/NN patients. Results showed that most patients with M2/t(8;21) were young males with higher incidence of extramedullary infiltrations. Complete remission rate was higher but with earlier relaps. The prognosis of patients with M2/t(8;21) with loss of one sexual chromosome was poor.     

t(8;21)急性髓性白血病预后分析

目的:研究伴t(8;21)的急性髓性白血病(AML)患者近期疗效。方法:30例伴t(8;21)的AML患者中M01例、M226例、M52例、CML-BPI例。26例伴有t(8;21)的M2患者中简单核型异常9例,复杂核型异常17例,取28例正常核型的M2患者为对照,观察染色体核型异常与化疗后完全缓解(CR)率的关系。结果:t(8;21)的非M2患者除1例M5经治疗为CR外,余3例均为NR;t(8;21)的M2患者的CR率(84.6％(22/26))高于正常核型的M2患者(64.3％(18/28))(P>0.05);简单核型异常的M2/t(8;21)患者化疗CR率(94.1％(16/17))高于伴复杂核型异常的M2/t(8;21)患者(66.7％(6/9))(P>0.05)。结论:t(8;21)的M2患者预后较好。而伴复杂核型M2/1(8;21)患者疗效相对较差。     

t(8;21)急性髓性白血病72例的特征分析

目的:探讨伴有t(8;21)染色体异常的急性髓性白血病(acute myeloid leukemia,AML)的实验室及临床特性,比较伴有附加染色体异常与单纯t(8;21)AML的差异.方法:回顾性分析72例t(8;21)AML患者,包括细胞形态学、血象、细胞遗传学G显带核型、免疫表型、AML1/ETO融合基因及临床特征,并按染色体核型分为单纯组(A组)及伴有附加异常组(B组)进行比较.结果:72例t(8;21)AML按FAB分型M2占65例(90%),M4占5例,2例为M5.单纯易位27例,伴附加染色体异常45例(62.5%),主要的附加异常类型为-Y, 4,del(9q).A,B两组在年龄分布、骨髓幼稚细胞数、骨髓Auer小体检出率、骨髓嗜酸细胞数、免疫表型分布、髓外白血病发生率及化疗诱导缓解率上差异无统计学意义,但B组初诊时外周血白细胞数略低,且男性患者比例明显高于A组.随访1～96月,A组3年预期生存率为(63.9±11.2)%,中位生存时间为65个月;而B组3年预期生存率为(20.9±9.2)%,中位生存时间12个月(P＜0.05),但B组各种主要附加异常之间生存时间差别无统计学意义.结论:附加染色体异常是t(8;21)AML预后不良的重要因素之一,伴有附加异常的t(8;21)AML生存时间明显短于单纯t(8;21)者.     

225例急性髓细胞白血病的细胞遗传学研究

目的 探讨急性髓细胞白血病(AML)的细胞遗传学改变及与诊断、治疗、预后的关系。方法 对225例初治AML的患者进行骨髓染色体分析，采用短期培养法制备骨髓细胞染色体G显带。结果 发现本组13l例(58．20%)有克隆性染色体异常。共有14种核型异常。t(15；17)、t(8；21)、t(9；22)为最常见的结构异常．且t(15；17)、t(8；21)、inv(16)分别仅见于M2、M2、M4B0。核型异常与临床完全缓解率，完全缓解持续时间及中位生存期等预后高度相关，t(15；17)、t(8；21)完全缓解率高．完全缓解期及中位生存期长，预后相对较好。而正常核型次之，其它核型异常预后较差。结论 染色体研究对AML的诊断，分型，治疗选择及预后估计均有重要意义。     

急性髓细胞白血病M2亚型细胞形态学及细胞遗传学分析

目的:了解急性粒细胞白血病AML-M2亚型的细胞形态学及细胞遗传学特征.方法:对23例以FAB分类标准确诊的AML-M2初发患者的细胞形态学及细胞遗传学资料进行回顾性分析;应用骨髓细胞短期培养法制备染色体标本,以R显带技术进行核型分析.结果:34%M2a、92%M2b患者白血病细胞内可见Auer小体,Auer小体在M2b患者细胞中检出率明显高于M2a患者;M2患者白血病细胞POX染色呈强阳性反应,在M2a细胞表达多为弥散细颗粒状,而在M2b呈局灶团块状.23例患者中18例有克隆性染色体异常,异常核型检出率78.3%(18/23).16例M2a患者无一致性的染色体异常.7例M2b患者均有特异性的t(8;21)异常,其中3例伴有y染色体丢失.结论:M2白血病组内异质性较大,M2a和M2b似乎具有各自独特的细胞形态学及细胞遗传学特性.     

间期荧光原位杂交检测核心结合因子相关急性白血病的初步研究

目的 应用间期荧光原位杂交技术(I-FISH)检测初诊急性白血病患者中核心结合因子(CBF)受累的染色体异常情况并对治疗后患者的微小残留病(MRD)进行监测，同时对I-FISH与常规染色体G显带的灵敏度进行比较。方法在骨髓形态学初筛的基础上，应用常规染色体G显带技术对15例急性髓系白血病(AML)进行核型分析，应用I-FISH对患者可能受累的CBF相关靶基因进行检测，其中7例患者治疗后进行了MRD监测。结果(1)正常对照组中，CYTOCELL公司提供的3种探针(AML1／ETO易位探针、MYH11基因断裂点双色探针和ETV6／AML1易位探针)的正常分界值分别为4．13％、1．95％和2．12％。(2)常规染色体G显带分析，15例患者中有6例伴有潜在累及CBF基因的染色体异常，其中8例AML-M2中5例伴t(18；21)，2例AML-M4EO中1例伴inv(16)，5例儿童B系急性淋巴细胞白血病(B—ALL)未检出相应的异常。I-FISH检测15例患者发现有12例累及CBF基因，其中8例AML-M2患者均为AML1/ETO融合基因( )，2例．AML-M4EO病人CBFμ／MYH11融合基因均为( )，5例儿童B-ALL，中2例ETV6／AML融合基因( )。(3)3例AML-M2患者中2例MRD阳性；2例M4EO患者治疗后MRD监测结果均阴性；2例B-ALL患者l例阴性m1例阳性。结论 I-FISH较常规染色体G显带技术能够更灵敏地检测出累及CBF的急性白血病。在初诊时联合应用这两种方法能使结果更趋全面和准确。     

儿童与少年急性非淋巴细胞白血病的细胞遗传学研究

对33例15岁以下急性非淋巴细胞白血病患者进行了细胞遗传学研究,21例(63.6％)有获得性染色体异常。15例为t(8;21),主要属M_2亚型。2例检出近四倍体克隆,皆属M_6.21三体,1q三体,t(15;17)和复杂异常各1例。前两者属M_2,皆由骨髓增生异常综合征演变而来,后两者分属M_3和M_5。     

Terminal deoxynucleotidyl transferase in various immunophenotypic cells in leukemia]

The staining results of terminal deoxynucleotidyl transferase (TdT) in leukemic cells of peripheral blood or bone marrow in 55 patients showed that 22 (40%) patients were found positive for TdT staining: 17 patients with acute lymphoblastic leukemia (ALL), 2 acute non-lymphocytic leukemia (ANLL) and 3 hybrid acute leukemia (HAL). The positive rate of ALL (17/21) was significantly higher than that of ANLL (2/21, P < 0.005). The leukemic cells of HLA-DR+CD19+TdT- were demonstrated to express some of myeloid restricted antigens (HI98, HIM 4, HIM 5) (3/3), which suggested that these cases were leukemias of myeloid origin. None of the 8 patients with M 0/M 1 ANLL was positively stained for the enzyme. Our results showed that TdT detection is of great value in the diagnosis and differentiation of both poorly differentiated and hybrid acute leukemia.     

All-trans retinoic acid as a single agent induces complete remission in a pat ient with acute leukemia of M2a subtype

Objective To present a special case with the karyotype and molecular marker of acute myelo id leukemia (AML)-M(2) who was induced to complete remission by all-trans reti noic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially d iagnosed as M(3) subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques an d RT-PCR were applied to further define the diagnosis. After primarily culture d bone marrow cells from the iliac aspiration were tested for in vitro induced d ifferentiation, the patient was treated with oral all-trans retinoic acid alone , 60 mg per day until complete remission was achieved. Peripheral blood and bo ne marrow changes were monitored over the whole treatment course. Results The characteristic chromosomal aberration for M(3) , the t(15;17) reciprocal tran slocation, was not found while a t(8;21) translocation was verified. Furthermor e, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα f usion gene was detected by RT-PCR and the diagnosis was corrected from M(3) to M(2) . Primary cultured bone marrow cells can be fully induced to terminal diffe rentiation after 4 days exposure to ATRA. A hematological complete remission wa s achieved after 40 days treatment with ATRA as a single therapeutic agent, sug gesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M(3) , such as M(2) in this case, ma y also be induced to complete remission by the mechanism of ATRA-induced termin al differentiation. This implies that there may be a pathway other than PML/RAR α fusion gene product which mediates ATRA-induced myeloid maturation in leukem ia cells.     

Correlation between growth pattern in vitro and karyotype of bone marrow cells and prognosis in adult acute nonlymphocytic leukemia

Summary Growth pattern in vitro and karyotype of cultured bone marrow cells were studied in 31 patients with acute nonlymphocytic leukemia. Two different growth patterns were identified: cluster growth (pattern I), and no growth (pattern ll). Patients with growth pattern I had a significantly higher complete remission (CR) rate clinically than those with growth pattern I. A serial study of 23 patients during induction treatment showed three different patterns: (1) colony growth, (2) persistence of clusters, and (3) persistence of no growth. The prognosis of the patients with the first pattern was most favourable, 11 of 13 patients achieved CR on an average of 24 days after first detection of colony formation. The data from 152 cultures showed that the colony forming ability had a negative correlation with the percentage of marrow blasts. Karyotype analysis with G-banding technique was successfully performed in 26 patients, in 14 of whom abnormal clones were detected. There was no difference in CR rates between groups NN, A A and AN, although CR was more easily achieved in patients with t(8; 2l). No relationship was seen between growth pattern and karyotype.     

t(8,21)易位急性髓细胞性白血病免疫学表型分析

用流式细胞仪检测21例t（8；21）易位急性髓细胞性白血病细胞的免疫学表型，并与无t（8；21）易位急性髓细胞白血病（M2）病人比较．结果：t（8；21） 组与t（8；21）-组CD1，阳性率分别为62％、9％（P＜0．01）．CD34阳性率分别为76.2％、36％（P＜0．05），t（8；21） 组中皆无表达CD7，而t（8；21）-组中CD7阳性率为27．2％（P＜0．05）；两组间CD15、CD13、CD33、CD10表达无显著差异．提示t（8；21）急性髓细胞白血病有独特的免疫学表型特点，对形态学分类法难以分类的急性白血病诊断有一定的价值．     

应用FISH检测儿童ALL TEL-AML1与E2A/PBX1融合基因

目的探讨TEL-AML1与E2A/PBX1融合基因在儿童急性淋巴细胞白血病（ALL）的检测方法及其临床应用价值。方法在形态学、免疫分型、细胞遗传学基础上,应用荧光原位杂交技术（FISH）检测63例ALL患儿TEL-AML1和E2A/PBX1融合基因阳性率。结果 FISH技术可以显著提高TEL-AML1和E2A/PBX1融合基因的检出率,TEL-AML1融合基因在初发ALL儿童中的阳性率为25.4%（16/63）,E2A/PBX1融合基因在初发ALL儿童中的阳性率4.8%（3/63）。结论 t（12;21）形成TEL-AML1融合基因和t（1;19）形成E2A/PBX1融合基因,是儿童ALL常见的染色体易位,常规染色体核型分析极难发现,需用FISH分子生物学检测方法加以证实。     

小剂量阿糖胞苷治疗17例急性非淋巴细胞白血病

Low dose Ara-C (LDAra-C, Ara-C 10-15 mg/12 h, i.m. x 14-21 days) was used in the treatment of 17 patients with ANLL, and from 14 patients blast cells were isolated before chemotherapy and cultured in the presence of Ara-C (10(-8) and 10(-7) mol/L), no definite induction of differentiation of leukemic cells was found. Of the 17 cases, 5 obtained CR, only one of them with M4 entered CR without pancytopenia or bone marrow aplasia during the LDAra-C treatment. For the rest, 4 with M2 obtained PR, and 8 did not respond. Toxic effects, including pancytopenia and bone marrow aplasia, were observed in most of the patients. Laboratory results showed that differentiation was not induced by Ara-C in low concentration in in vitro culture. LDAra-C is thought to be effective in the treatment of ANLL, and the mechanism may involve both the cytotoxicity and the induction of differentiation of leukemic cells, but the former is far more important.     

急性非淋巴细胞白血病26例的核型与临床和预后的关系

31例未治ANLL中26例的骨髓细胞染色体G显带成功。14例有核型异常(53.8％)。其中5例为t(8;21)。按核型正常或异常分组,其完全缓解率无显著差异,但t(8;21)异常的病例具有共同的血液学和临床特点,较易获得缓解。对16例病人作了动态观察,发现在诱导缓解期两例病人的核型较细胞形态学能更早反映或证实化疗效果。认为动态核型研究是判断疗效的较客观可靠的指标。     

42例慢性粒细胞白血病额外染色体异常的临床分析

目的探讨慢性粒细胞性白血病(CML)继发额外染色体异常临床经过与预后的关系。方法对42例CML患者从初诊到急变6个月至8年病程期间，采用短期培养法进行骨髓细胞染色体分析，并动态观察染色体变化。结果42例CML初诊时均出现pH染色体，11例在加速期和急变期出现均不相同的额外染色体异常，除 8、 21、i(17q)和2ph国内有报道外，r(2)、t(8；20)、t(3；11)、t(2；3)、t(10，18)及del(16)(q11)、 12等异常属少见。结论CML病程中继发额外染色体异常无克隆性特征，但可预示CML疾病的恶化，经过凶险，预后不良。     

骨髓增生异常综合征75例临床分析

目的　进一步认识骨髓增生异常综合征 (MDS)的临床、血液学和骨髓病态造血的特点。方法　对 1995年 1月～ 2 0 0 2年 1月确诊的 75例MDS患者的一般情况、临床和实验室检查特点进行总结分析。结果　 75例MDSFAB分型难治性贫血 (RA) 46例 ,难治性贫血伴环状铁粒幼细胞增多 (RAS) 4例 ;按WHO 1997新诊断标准真正RA(包括RAS 2例 )仅 8例 ,有 3 9例属于“难治性血细胞减少伴多系增生异常 (RCMD)”范畴。 72例 ( 96%)和 3 9例 ( 5 2 %)患者分别有贫血和全血细胞减少 ,2 2 .6%患者在外周血片可见到有核红细胞 ,16%见到幼稚粒细胞 ,2 .6%见到小巨核细胞 ;T细胞亚群显示明显异常 ,骨髓中红系祖细胞体外培养集落明显减或缺如。 2 5例患者染色体检查 12例检出异常核型 ,以5q 和t( 8;2 1)平衡易位较常见 ;复杂核型多见于MDS RAEB或RAEB t患者。骨髓中红、粒巨幼样变分别占 2 7.3 %和 2 4%,小巨核细胞检出率占 3 0 .7%,骨髓活检示幼红细胞岛和未成熟前体粒细胞位置异常 (ALIP)现象分别占 3 3 .3 %和 5 2 .8%。RA和RAS采用雄激素为主的治疗 ,62 %( 3 1/5 0 )血红蛋白有所提高 ,RAEB和RAEB t大多转化急性白血病。结论　应加强对WHO分型新标准的认识 ,骨髓病态造血特别是ALIP和小巨核的检出对诊断具有重要价值并可能反映     

荧光原位杂交检测骨髓增生异常综合征患者染色体复杂核型变化及临床意义的研究

目的:探讨骨髓增生异常综合征(MDS)患者复杂核型变化及其临床意义。方法:在常规细胞遗传学(CC)方法检测基础上,运用荧光原位杂交技术(FISH),采用多种位点特异性DNA探针(染色体全染、特殊位点、双色易位融合探针)对35例MDS患者进行染色体核型分析。结果:35例MDS患者中有24例出现染色体异常,包括染色体数目及结构的异常,阳性率占68.6%。其中6例出现5号染色体单体或5号染色体长臂丢失;4例出现7号染色体单体或7号染色体长臂丢失;1例出现等臂7号染色体;2例出现8号染色体三倍体;3例出现Y染色体丢失;2例出现16号染色体倒位;5例出现复杂的染色体易位,包括t(6;?),(t8;21)(q22;q22),(t7;?),der(19)(t19;?)(q13.3;?),der(9)(t9;?)(p11;?)(t6;9),(t8;14),(t1;8)。结论:FISH技术在MDS染色体核型分析上可作为重要技术补充手段弥补CC检查的不足,对MDS准确诊断分型、合理治疗方法的选择乃至对预后的评估都具有重要的临床意义。     

Granulocytic sarcoma causing cord compression in a pregnant woman with acute myeloid leukemia and t(8;21)

Chloroma or granulocytic sarcomas (GSs) are solid tumors originating from myeloid precursors. Most frequently they occur in acute myeloid leukemia (AML), myeloproliferative disorder, and myelodysplasia. It may involve any organ system, but mostly it affects the bone and soft tissue of the head and neck. Granulocytic sarcoma resulting in spinal cord compression is rare. The association between t(8;21), and GS has been reported. In spite of the fact that t(8;21) is considered to be associated with good prognosis, patients with GS and spinal cord compression had less favorable prognosis than other AML patients with t(8;21). Radiotherapy, chemotherapy, and surgical decompression are the accepted methods of therapy. However, aggressive therapy such as transplantation may be warranted early in the therapeutic strategy. Pregnancy associated with AML is rare. In our research, only one case of pregnancy with GS and AML has been previously reported. We are reporting a pregnant female diagnosed with AML/M2 with t(8;21) at the first trimester, who relapsed with GS, and cord compression at full term. She had a normal baby, and achieved second remission post-chemotherapy. Unfortunately, shortly after this she had a relapse, and died.     

中剂量阿糖胞苷对急性髓系白血病M2的疗效分析

目的:观察中剂量阿糖胞苷(ID-Ara-C)在急性髓性白血病(AML)M2缓解后巩固强化治疗中的疗效。方法:AML-M2在诱导缓解后,先予两个标准剂量巩固治疗,之后采用ID-Ara-C强化治疗,分别观察t(8;21)患者组与正常核型组的复发率、无病生存率以及总生存率。结果:t(8;21)患者组复发率为46.1%,低于正常核型组的复发率(61.9%);5年无病生存率为53.9%,高于正常核型组的38.0%,两组数据差异有显著性意义(P<0.05)。结论:对于AML-M2患者在第1次诱导缓解治疗后,应用4个周期含ID-Ara-C方案进行个体化巩固强化治疗,可以降低复发率,减少治疗相关死亡率。