急性髓系白血病细胞异常免疫表型表达的研究

应用免疫酶标染色法检测了５９例急性髓系白血病患者的白血病细胞免疫表型，结果表明，ＣＤ２，ＣＤ５，ＣＤ７，ＣＤ１０，ＣＤ１９，ＣＤ２２淋系抗原的表达率分别为１６．９％，１１．９％，１６．９％，１５．３％，１０．２％和６．８％。进一步分析结果表明，在Ｍ３病例细胞中，ＣＥ２，ＣＤ１０和ＣＤ１９抗原表达阳性率明显高于Ｍ５组，而ＣＤ７抗原表达阳性率明显低于Ｍ５组。     

双表型急性白血病流式细胞术免疫分型检测结果

 目的　应用流式细胞术（FCM）检测双表型急性白血病（BAL）的免疫表型。方法　采用四色FCM检测23例BAL患者的免疫表型。结果　23例BAL患者中有10例（43.4 %）表达cCD3,16例（69.6 %）表达cCD79a,20例（87.0 %）表达cMPO,14例（60.9 %）表达TdT,19例（82.6 %）表达CD34,20例（87.0 %）表达CD117,同时表达髓系和B系抗原者13例（56.5 %）,均共同表达cCD79a和cMPO;同时表达髓系和T 系抗原者7 例（30.4 %）,均共同表达cCD3和cMPO;同时表达T系和B系抗原者3例（13.04 %）,均共同表达cCD3和cCD79a。结论　cCD3、cCD79a、cMPO为系列特异性抗原标志,对诊断及鉴别BAL具有重要意义,FCM是目前诊断BAL特异可靠的方法,在临床白血病治疗和预后方面有重要的指导意义。     

急性髓系白血病细胞异常免疫表型表达的研究

应用免疫酶标染色法检测了59例急性髓系白血病（AML）患者的白血病细胞免疫表型，结果表明CD2、CD5、CD7、CD10、CD19、CD22淋系抗原的表达率分别为16．9％（10／59）、119％（7／59）、16．9％（10／59）、15．3％（9／59）、102％（6／59）和6．8％（4／59）。进一步分析结果表明，在M3病例细胞中，CD2、CD10和CD19抗原表达阳性率明显高于M5组，而CD7抗原表达阳性率则明显低于M5组。结合临床，CD2、CD19阳性的AML病例对化疗治疗及应优于CD2、CD19阴性的AML病例；CD7阳性的AML病例的疗效与预后则比CD7阴性的AML病例差。提示部分AML病例的白血病细胞存在不同程度异常免疫表型的表达，且与疗效及预后有一定关系。     

成人急性双表型白血病的临床和生物学特征研究

目的：分析成人急性双表型白血病（BAL）的临床和生物学特征.方法：采用流式细胞术检测22例成人BAL患者治疗前骨髓细胞的免疫表型,染色体R显带技术对其中的16例进行核型分析.结果：在同期急性白血病496例患者中BAL发生率为4.4%（22/496）,16例（72.7%）为髓系和B系抗原共表达,5例（22.7%）为T系和髓系 抗原共表达,T系、B系和髓系均表达者1例 （4.5%）.BAL患者CD34阳性率为86.4%,高于同期ALL（60.3%）和AML（62.9%）（P＜0.05）.BAL患者中位年龄大于ALL患者（P＜0.05）.BAL组肝、脾、淋巴结肿大例数明显高于AML组（P＜0.01）.BAL组异常核型占56.3%,Ph染色体阳性率（25%）明显高于AML组（0%）（P＜0.01）.结论：成人BAL发病率低,以髓系和B淋巴系抗原共表达为主.BAL患者发病中位年龄高,高表达CD34,Ph染色体阳性者多见,肝、脾、淋巴结浸润发生率高.     

双表型急性白血病的临床与实验研究

目的研究双表型急性白血病(BAL)生物学特征和临床特征.方法对539例成人急性白血病(AL)进行MIC分型实验研究并对其中的7例进行临床治疗结果观察研究.结果①BAL有36例占总AL的6.7%.②36例BAL中B-髓系占63.9%、T-髓系22.2%和T-B-髓系13.9%.③36例BAL中CD34阳性率75.0%.④36例BAL中正常核型52.8%、异常核型47.2%,Ph染色体占总BAL的22.1%、异常染色体BAL的47.2%.⑤治疗结果:7例BAL中CR 4例、NR 3例,CR 4例中3例系t(8;21)、并且系CD19阳性的B-髓系BAL.结论BAL的发生率很低,以B-髓系最常见,高表达CD34.预后与染色体核型有关.     

急性双表型白血病细胞遗传学分型特征的研究

背景与目的：自1995年白血病免疫分型欧洲协作组（EGIL）推荐了一套积分系统用于白血病免疫分型以来,关于急性双表型白血病（BAL）的细胞遗传学特征国内外均有报道,但病例数较少,本文研究了一组BAL的细胞遗传学分型特征。方法：56例BAL患者骨髓标本进行细胞形态学及细胞化学染色,确定其FAB亚型;运用一组系列相关单克隆抗体和流式细胞仪及直接免疫荧光标记技术进行免疫分型;采用热变性姬姆萨R显带法（reverse heating giemsa,RHG)进行核型分析。结果：本组资料揭示BAL患者细胞遗传学改变具有异质性,正常核型占44.4%,克隆性异常占55.6%。在克隆异常中Ph染色体改变占23.2%高于对照组AML组（0%）,且在B淋系、髓系共表达患者组中（39.3%)高于T淋系、髓系共表达患者组（0%）。其它相关性克隆性染色体异常有t(8;21)、t(15;17)、t(9;22)、inv(16)、非相关性染色体异常有t(12;17)、t(14;15)、t(3;6)、 21、复合异常等。结论：BAL患者Ph染色体改变具有普遍性,说明它起源于比较早期的造血干/祖细胞。     

成人急性双表型白血病的临床研究

目的 研究急性双表型白血病（BAL）的临床生物学特征和预后。方法 63例BAL患者骨髓标本分别进行细胞形态学及细胞化学染色,确定其FAB类型,运用一组系列相关单抗和流式细胞仪及直接免疫荧光标记技术 进行免疫分型,同时采用反转热变性姬姆萨（RHG）显带技术进行核型分析。运用针对急性髓性白血病（AML）,急性淋巴细胞白血病（ALL）或二者兼顾的方案治疗。结果 BAL患者的临床表现与AML和ALL患者差异无显著性。形态学上AML以M5、M1、M2亚型,ALL以L2、L1亚型居多,免疫分型显示,BAL患者中以髓系与B系抗原共表达为主,另外,CD34在BAL中高表达,提示BAL可能起源于较早期的造血干或（和）祖细胞,核型分析显示,BAL中Ph染色体较多见,占25.5%(13/51)。BAL患者对治疗反应差,生存期较短。结论 BAL具有独特的临床,生物学和预后特征。     

急性髓细胞白血病免疫表型特点及与预后的关系

对１１１例原发、初治的急性髓细胞白血病（ＡＭＬ）患者进行了免疫表型及ｐ１７０检测。同时对可判断疗效的８０例患者（不含Ｍ３）进行了免疫表型与预后关系分析，结果显示：Ｍ３患者ＣＤ１３、ＣＤ３３高表达、ＣＤ３４、ＨＬＡ－ＤＰ、ｐ１７０均为阴性，Ｍ２ａ患者ＣＤ７高表达而ＣＤ１４、ｐ１７０阳性率较低；Ｍ２ｂ患者ＣＤ７为阴性，Ｍ４、Ｍ５的特点相似，ＣＤ１４、ＣＤ１５、ＣＤ３８、ＣＤ３３、ＨＬＡ－ＤＰ均高表达，ＣＤ７弱表达，ｐ１７０阳性率较高。免疫表型与ＡＭＬ预后关系分析结果显示ＣＤ３４、ＣＤ１５与治疗反应显著相关。而ＣＤ１４、ＣＤ７、淋系相关抗原与预后的关系不明显。     

白血病髓外浸润相关微环境

白血病细胞的髓外组织浸润是导致白血病患者复发、死亡的重要原因之一,越来越多的研究显示髓外微环境在白血病进展和复发中发挥重要作用.白血病髓外浸润的发生是多因素、多步骤相互作用的结果,涉及肝、脾、中枢神经系统、胸腺等各组织器官.     

Extramedullary sites of leukemia relapse after transplant

Recurrent or residual leukemia found in extramedullary sites after intensive treatments adversely affects prognosis. To summarize the sites and outcomes when extramedullary relapses have been reported after stem cell transplants, and to elucidate when long survival has been achieved, 207 cases were analysed. Authors were contacted for follow-up information. The most commonly reported sites are soft tissue in acute leukemias and bone in CML. Extramedullary relapse occurred typically within 2 years in ALL, but later in one-third of myeloid leukemias. Most testicular relapses reported in AML followed non-TBI conditioning. Marrow relapse was not inevitable if aggressive treatment was begun early. Local therapy alone was generally inadequate. Intensive therapy has produced lengthy remissions in cases of acute leukemias involving various sites, whereas CML cases, particularly involving bone, were most resistant to treatment. Heightened awareness and aggressive treatment should improve the prospect for cure after extramedullary relapse.     

Extramedullary lesions in non-lymphocytic leukemia: results of radiation therapy

Fifty-four courses of radiotherapy were given to 33 patients with symptomatic extramedullary involvement by non-lymphocytic leukemia. Among them were 23 cases of granulocytic sarcoma. Analysis of the treatment response showed that age, hematopathologic type and quality of irradiation did not influence the radiation response. However, a dose response relationship could be demonstrated with a statistically significant difference in response among the four groups of patients treated to total doses of less than 1000 rad, 1000-1999 rad, 2000-2999 rad, and greater than or equal to 3000 rad (p = 0.003). We suggest irradiating all extramedullary lesions to at least 1100 ret.     

Natural killer cell lymphoma/leukemia: pathology and treatment

Malignancies arising from cells of putative natural killer (NK) cell origin have increasingly been recognized as distinct clinicopathological entities. These malignancies are marked by tumour cells with NK cell characteristics, including the immunophenotype of CD2⁺, surface CD3⁻, cytoplasmic CD3ϵ+, CD7±, and CD56+, and the genotype of germline T cell receptor gene. A consistent association with monoclonal Epstein–Barr virus infection in the tumour cell has been observed. These tumours are now regarded as putative NK cell lymphoma/leukemia. Pathologically, tumour cells show variable cytological appearances, with frequent angiocentricity and angioinvasion, associated with zonal necrosis. Clinically, most cases occur in the nasal area and upper aerodigestive tract. However, occurrence in non-nasal sites such as the skin, gastrointestinal tract and testis is also observed. A particularly aggressive form of NK lymphoma/leukemia presents fulminantly as disseminated disease sometimes with a leukemic phase. All types of NK lymphoma/leukemia have an extremely poor prognosis with a median survival of less than a year. New modalities of treatment, including the use of high dose chemotherapy and stem cell rescue may be needed to improve treatment outcome. © 1997 John Wiley & Sons, Ltd.     

Malignant lymphomas in Japan: epidemiological analysis on adult T-cell leukemia/lymphoma

According to the Vital Statistics Japan Series in 1950-1981, the age-adjusted death rate for malignant lymphomas (ICDs, 200-202) in Japan has increased in recent years. A geographical clustering of malignant lymphomas in the Kyushu districts was observed both in the period 1969-1971 and more recently in 1979-1981. The excessive rate of malignant lymphomas in Kyushu was due to the high incidence of adult T-cell leukemia/lymphoma (ATLL). The distribution of healthy carriers of ATLV, a human retrovirus which is almost identical to HTLV, was closely related to that of patients with ATLL in Japan. Epidemiological features of the infectious mode of ATLV suggested two main routes of natural transmission, one from mother to child and the other from husband to wife. ATLV is considered to be a main causative agent of ATLL from virological and epidemiological evidence, but infection by this virus alone may not result in ATLL because the incidence of ATLL among ATLV carriers was apparently not very high even in endemic areas of ATLL. Thus, some risk factors other than ATLV, such as environmental and genetic factors, may contribute to the development of ATLL.     

T淋巴母细胞白血病／淋巴瘤分子遗传学研究进展

T淋巴母细胞白血病／淋巴瘤（T-ALL／LBL）是一种定向于T细胞系的淋巴母细胞恶性肿瘤,临床治疗效果差。其分子遗传学主要与抗原受体基因异常、染色体异常、癌基因激活、抑癌基因失活和分子通路改变等多方面因素有关。文章就T-ALL／LBL的最新分子遗传学研究进展进行阐述,旨在探索与其预后的相关指标及可能的治疗靶点。     

Different prognostic factors for survival in acute and lymphomatous adult T-cell leukemia/lymphoma

Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a clinically aggressive and heterogeneous entity; hence it is likely that different variants of ATLL have different prognostic factors. Methods: 95 patients with ATLL seen at our institution between 1987 and 2008 were included. Clinical data were compared, according to ATLL variant, using the Mann-Whitney and the Chi-square tests for continuous and categorical variables, respectively. Kaplan-Meier estimates compared using the log-rank test and Cox proportional-hazard test were used for the univariate and multivariate analysis, respectively. Results: Median age was 61 years with male-to-female ratio of 1.07:1. Patients with acute ATLL were more likely to present with bone marrow, liver and spleen involvement, higher β2-microglobulin and lower albumin levels. Poor performance status, high IPI score, presence of B symptoms, high LDH and low albumin levels were associated with a worse survival in lymphomatous ATLL. High LDH, high β2-microglobulin and high PIT score were associated with worse survival in acute ATLL. In the multivariate analysis, low albumin level and presence of B symptoms were independent factors for worse survival in lymphomatous ATLL, and high β2-microglobulin level was independent factor for worse survival in acute ATLL. Conclusions: Aggressive ATLL variants have a distinct, almost mutually exclusive profile of prognostic factors.     

Prognostic Impact of Extramedullary Infiltration in Pediatric Low-risk Acute Myeloid Leukemia: A Retrospective Single-center Study Over 10 Years

BackgroundThe impact of extramedullary infiltration (EMI) on the clinical outcomes of pediatric patients with acute myeloid leukemia (AML) are controversial.Patients and MethodsA total of 214 pediatric patients with low-risk AML were classified as having EMI (central nervous leukemia [CNSL] and/or myeloid sarcoma [MS]) and not having EMI. Patients with isolated MS before AML diagnosis by bone marrow examination were confirmed with histopathologic examination. For patients diagnosed with AML by bone marrow examination, a thorough physical examination and radiologic imaging were used to confirm MS.ResultsMale gender, a high white blood cell count, the FAB-M5 subtype, t(8;21) and t(1;11) abnormalities, and c-KIT mutations were associated with EMI. The presence of MS was associated with a low complete remission rate (63.6% vs. 79.4%; P = .000) and poor 3-year relapse-free survival (RFS) (62.6% ± 7.5% vs. 87.0% ± 2.8%; P = .000) and 3-year overall survival (73.5% ± 7% vs. 88.8% ± 2.6%; P = .011). Multivariate analysis revealed that MS was a poor prognostic factor for RFS and overall survival. Bone infiltration was an independent risk factor for inferior RFS with MS. Patients with CNSL had a low complete remission rate (58.3% vs. 77.2%; P = .045); however, CNSL did not significantly affect the survival of low-risk patients with AML.ConclusionMS should be considered an independent risk factor to guide stratified treatment.     

Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases

We analysed the clinical and pathologic features of 42 patients with immunologically confirmed peripheral T-cell lymphoma. The median age was 60 years and the male to female ratio was 1:1. A prior lymphoproliferative or autoimmune disorder was present in 14 per cent of the patients. Signs of advanced disease were usually present from the onset, such as B symptoms (55 per cent), generalized lymphadenopathy (57 per cent), stage III/IV disease (62 per cent), and elevated levels of serum lactate dehydrogenase (68 per cent). Primary extranodal disease (14 per cent), hepatomegaly (12 per cent), splenomegaly (12 per cent), lung/pleural involvement (12 per cent), skin involvement (21 per cent), and bone marrow involvement (28 per cent) were uncommon. Lymphocytopenia was present in 64 per cent of the patients, and none of nine patients tested were serologically positive for human T-cell leukemia/lymphoma virus (HTLV-I) infection. Among 38 patients receiving combination chemotherapy, 20 (53 per cent) achieved a complete remission. The actuarial median survival of all patients was 17 months. Age greater than 60 years and stage III/IV disease predicted a poor clinical outcome, whereas the large cell histological subtype predicted a favourable outcome. Prospective clinical studies using uniform treatments and a uniform histologic classification scheme are needed to confirm these findings.     

Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas,including mantle cell lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis.