慢性中性粒细胞白血病五例临床分析

慢性中性粒细胞白血病(chronic neutrophi licleukemia，CNL)是一种罕见的白血病，最新的WHO国际血液肿瘤分类标准中已将CNL作为慢性骨髓增殖性疾病(MPD)的独立分型。随着对本病认识的不断提高，发病率有增高趋势，现对我院诊断的5例CNL作一分析，探讨其诊断、治疗及预后特点。     

慢性中性粒细胞白血病2例

例 1　男, 61 岁。因全身乏力,纳差,腹胀就诊。轻度贫血貌。体检: T 37.2℃,全身表浅淋巴结不大,巩膜无黄染,皮肤黏膜无出血点,胸骨无压痛,心肺检查无异常, X 线:胸片未见感染。B 超示:肝轻度肿大,巨脾。实验室检查:Hb 100 g/L,WBC 35.3×109/L, PLT 230×109/L;分类: N89%,L 11%,未见幼红、幼粒细胞,成熟红细胞无明显异常。尿、大便常规,乙肝(-)、肝功能、肾功能均正常,入院后检查未见感染,无发热,为清除潜隐感染,先后用青霉素、先锋霉素等抗生素治疗,WBC仍在(32.0 ~ 35.5)×109/L 之间,为明确病因故行骨髓穿刺检查。骨髓象:…     

慢性中性粒细胞白血病三例

慢性中性粒细胞白血病(CNL)是少见的一种慢性骨髓增生性疾病。随着人们对此病的认识水平的提高,近几年的报道已明显增多。我院近年收治3例,现报道如下。临床资料例1,女,58岁,因“疲乏无力4个月,发现腹部包块1个月”入院,患者于1个月前自觉腹部有一包块,遂行腹部B超示,脾脏重度肿大,查血常规示:Hb142g/L,Plt73×109/L,WBC13.0×109/L,N0.89。入院查体:浅表淋巴结未触及肿大,胸骨无压痛,心肺无异常,脾脏重度肿大,质硬,无压痛。骨髓检查:增生明显活跃,粒系占72.5%,以杆状及分叶核为主,占52.5%,全片见巨核细胞32只,产板巨2只,余为颗粒巨,…     

慢性中性粒细胞白血病1例

1 病例介绍 患者,女,62岁。因右侧肢体运动障碍、失语,经当地医院诊断脑血栓给予活血化瘀治疗15天无效,于1991年12月17日转入我院。既往无高血压、糖尿病、冠心病史。T36.5℃,P84次/分,BP13.3/8.0 kPa(100/60 mmHg)。神志清晰,无黄疸,全身浅淋巴结不大,扁桃体不大,心肺(一),肝脾肿大。胸片:老年性慢性支气管炎改变。EKG示完全性左前分支传导阻滞。B超:肝助下5cm,回声均质,脾厚5.5cm,肋下4cm。CT:左侧多发性脑梗塞。Hb171g/L,RBC5 800×10~9/L,WBC34.9×10~9/L,N 0.92,LO.08,BPC448×10~9/L,LDH249U/L(正常值60～130),肝功、肾功、血糖、血脂、尿常规均正常,大便未见虫卵,1:200O OT试验阴性。经用川芎嗪、脑复康等治疗20余天,神经功能有所恢复,可下地活动,但血象持续异常,先后11次结果为:WBC     

慢性中性粒细胞白血病1例

慢性中性粒细胞白血病（CNL）是一种罕见白血病,WHO的国际血液肿瘤分类标准已将其作为慢性骨髓增殖性疾病（MPD）的独立分型。1920年由Touhy首次报告,至2001年西方文献的报告不足100例,1977—2001年的25年间我国文献报告CNL76例。我院收治1例CNL患者,现报告如下。     

慢性中性粒细胞白血病分子诊断研究进展

慢性中性粒细胞白血病(chronic neutrophil leukemia,CNL)是一种极为少见的BCR-ABL阴性骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN),其特征是持续地外周血成熟中性粒细胞明显增多、骨髓粒系增生和肝脾肿大,无髓系细胞发育异常形态改变和BCR-ABL1、P...     

慢性中性粒细胞白血病诊治进展

慢性中性粒细胞白血病(CNL) 是一种罕见但可致命的慢性骨髓增殖性肿瘤。其临床特征主要包括以中性 粒细胞为主的白细胞升高超过25×109/L,且不伴有病态造血或其他骨髓增殖性肿瘤及生理性中性粒细胞升高。 CSF3R T618I 突变是CSF3R 的激活突变。近期的研究揭示了该突变在CNL 发病中的重要作用。目前,CSF3R 突 变已经被纳入CNL 诊断标准。其他突变包括SETBP1 及ASXL1 ,也在疾病发病及进展中发挥着重要作用,且对药 物治疗的反应有关。个体化治疗时代,CNL 的目标是基于疾病临床特征及分子生物学特征的诊断和治疗。     

以血尿为首发表现的慢性中性粒细胞白血病一例

患者,男,78岁,退休教师。因“排尿困难、尿血1天”于2009年9月就诊,门诊行耻骨上穿刺尿液抽吸后收住泌尿外科。既往有“前列腺增生、尿道狭窄”行“前列腺部分电切、尿道扩张术”多年。有高血压、冠心病病史。     

慢性中性粒细胞白血病急性变一例

慢性中性粒细胞白血病急性变一例陶天文汪声恒患者女，６４岁。１９８９年２月２９日，因鼻出血就医。发现血象ＷＢＣ２８×１０９／Ｌ，多次复查，均＞２０×１０９／Ｌ。于４月１２日第１次入院。其他病史无特殊。入院查体：血象Ｈｂ１００～１３６ｇ／Ｌ，ＷＢＣ（１５...     

慢性粒细胞白血病353例的染色体核型分析

染色体核型分析对于慢性粒细胞白血病 (慢粒 )的诊断、鉴别诊断以及疗效观察具有重要意义。我院 1995年以来收治的 35 3例慢粒的染色体核型资料作一回顾性总结 ,以探讨其细胞遗传学特点和意义。一、资料与方法1 对象 :35 3例慢粒病例为 1995年 1月～ 2 0 0 1年 2月的门诊或住院患者 ,其中男 2 38例 ,女 115例 ,男女比为 2 0 7∶1,年龄 12～ 78岁。临床分期 :慢性期 (ＣＰ) 310例 ,加速期 (ＡＰ) 3例 ,急变期 (ＢＣ) 4 0例 ,后者中有 9例初诊时为慢性期 ,分别于 2个月至 5年后发生急变。慢粒的诊断和分期参照文献 [1]。2 染色体分析 :染色…     

Chronic neutrophilic leukemia

Summary Chronic neutrophilic leukemia (CNL) is a very rare entity, which has to be included among the chronic myeloid leukemias. Once an underlying cause of neutrophilia is excluded, the diagnosis of CNL is based on exclusion of chronic granulocytic and other types of chronic myeloid leukemias. The classification proposed by Sheperd et al. has proven to be helpful, but it must be completed by cytogenetic analysis and the search for bcr rearrangement by molecular biology methods, in order to confirm the absence of Philadelphia chromosome and of bcr-abl hybrid gene. We report here four cases of CNL, with confirmed absence of bcr rearrangement in two cases. Two patients died, 12 and 8 years after diagnosis, the second one following transformation into myelofibrosis with myeloid metaplasia. The other two died of acute myelogenous leukemia, the first one, 25 years after diagnosis of CNL, following a 3-year phase of acceleration. The last patient presented combined features of CNL and refractory anemia with excess of blasts, and was characterized by both progressive leukocytosis and severe thrombocytopenia; acute transformation into acute myelogenous leukemia occurred 6 months after diagnosis and death 1 month later. Among the 30 cases reported so far, plus the four presented here, combined myelodysplastic features were observed in five cases and transformation into acute myelogenous leukemia in six. Chronic neutrophilic leukemias should be reported regularity, in view of the uncertain and low frequency of this hematological disease.     

Deletion of the long arm of chromosome 20 in a patient with chronic neutrophilic leukemia: Cytogenetic findings in chronic neutrophilic leukemia

We encountered a 67-year-old female with chronic neutrophilic leukemia (CNL). Cytogenetic study showed she had a deletion in the long arm of chromosome 20. This finding indicates that CNL, in this case, is a clonal disorder. Most CNL patients have normal karyotypes, and only four patients with cytogenetic abnormalities, including two cases who received chemotherapy before the cytogenetic abnormality was detected, have been reported. Four of those cases, including our case, had abnormalities in the long arm of chromosome 20. This locus may be associated with the development of CNL. To our knowledge, this is the first case with CNL who showed deletion of the long arm of chromosome 20 before treatment was started. Am. J. Hematol. 54:72–75, 1997 © 1997 Wiley-Liss, Inc.     

Rapid detection of chimeric bcr/abl mRNAs in acute lymphoblastic and chronic myeloid leukemia by the polymerase chain reaction

Summary We have developed a rapid method for the detection of bcr/abl mRNAs, the products of the BCR/ABL fusion genes. The method is based on the polymerasechain-reaction (PCR). Through the use of additional internal primers it is possible to detect directly a single Ph¹-positive cell among 10⁵ unaffected cells thus omitting time-consuming blotting procedures. The whole analytical procedure starting from RNA isolation to agarose gel electrophoresis including two rounds of PCR can be performed in less than six hours.Supported by the Wilhelm Sander-Stiftung, Neustadt/Donau and the Deutsche Krebsgesellschaft, Landesverband Berlin     

甲磺酸伊马替尼治疗120例慢性髓性白血病的临床研究

目的观察甲磺酸伊马替尼（IM）治疗Ph染色体阳性和（或）BCR／ABL基因阳性的慢性髓性白血病（CML）的疗效和安全性。方法对90例Ph染色体阳性和（或）BCR／ABL基因阳性CML慢性期（CP）患者,持续口服IM,400mg／d;30例CML疾病进展期（加速期／急变期）患者,持续口服IM,600mg／d。服药期间定期复查血常规、骨髓细胞学、染色体和（或）BCR／ABL基因等指标,并随访观察。结果（1）CML—CP患者总的完全血液学缓解率（CHR）、完全细胞遗传学缓解率（CCyR）和完全分子遗传学疗效（CMR）分别为73．3％（66／90）、66．7％（60／90）、54．4％（49／90）;治疗前是否接受过干扰素治疗对CHR、CCyR和CMR均无明显影响;服药前病程≤6个月的CMR优于〉6个月者。初次达到CHR的时间与首次达CCyR的时间、首次达CCyR的时间与BCR／ABL首次转阴时间之间均存在相关性,而初次达CHR的时间与BCR／ABL首次转阴时间则无明显相关性。（2）进展期CML患者的CHR、CCyR、CMR分别为43．3％（13／30）、25．9％（7／27）、25．0％（7／28）,总病死率为30．0％（9／30）。（3）年龄≤25岁患者的病死率高于〉25岁者,差异有统计学意义（P〈0．05）。（4）白细胞减少达Ⅲ级者有19例（16．0％）,发生于治疗后5～20周。血小板减少达Ⅲ级者有21例（18．0％）,发生于治疗后3～16周。主要的非血液系统毒性为双下肢水肿、骨痛和皮疹等,但均程度轻微。结论IM对初治CML及经干扰素治疗失败的CML有较高的CHR及CCyR且起效迅速,对CML—CP疗效显著优于进展期;不良反应程度轻微,患者易于耐受。     

Chronic neutrophilic leukemia with marked myelodysplasia terminating in blast crisis

Summary A case of chronic neutrophilic leukemia (CNL) is reported. The patient had a history of bleeding, and showed sustained mature neutrophilic leukocytosis, hepatosplenomegaly, a high leukocyte-alkaline phosphatase score, elevated serum vitamin B₁₂ and uric acid, and the presence of Döhle bodies in the neutrophils. In addition to the above typical features, marked myelodysplastic changes in the erythroid and megakaryocytic series were observed in the bone marrow. Three months after the diagnosis of CNL had been established, the hematological picture evolved into a blast crisis of monocytic type. Such findings give support to the statement of CNL as a distinct entity belonging to the spectrum of the myeloproliferative disorders.     

Successful alpha-2b-interferon therapy for chronic neutrophilic leukemia

The authors report two patients with characteristic features of chronic neutrophilic leukemia (CNL) treated with alpha-2b-interferon (IFN) (Schering-Plough). At initiation of therapy, both patients had progressive disease and presented with large tumors. A rapid reduction of the tumor mass and a long-term stabilisation of the myeloproliferative disorder was obtained (therapy duration 16 and 26 months, respectively, and presently ongoing). In one patient, the dose of IFN could be significantly reduced during maintenance without relapse. Neither presented infectious or hemorrhagic complications under therapy. Alpha-2b-interferon is active and safe in CNL, even pretreated and progressive. It can also correct the neutrophil and natural killer functional defects frequently observed in CNL.     

Neutrophil function and cytokine-specific signaling in chronic neutrophilic leukemia

We diagnosed an 86-year-old woman with chronic neutrophilic leukemia (CNL) because she showed sustained leukocytosis dominated by mature neutrophils, hepatosplenomegaly, high neutrophilic alkaline phosphatase score, absence of the Ph chromosome, low serum level of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and no evidence of leukemoid reaction. We found that the extent of stimulation of her neutrophil functions by G-CSF and GM-CSF was greatly reduced compared to healthy donars neutrophils. We showed that CNL neutrophils have intact expression of granulocyte colony-stimulating factor receptor (G-CSFR) and granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR). This suggests that failure of enhancement by G-CSF and GM-CSF in CNL neutrophil functions might be due to disturbances in the intracellular domains of G-CSFR and GM-CSFR, regardless of external cytokine stimulation. However, the patient's neutrophils did not show any mutations in the G-CSFR and GM-CSFR intracellular critical regions. We also showed that stat3 and mitogen-activated protein kinase activation by G-CSF or GM-CSF in the patient's neutrophils were significantly lower than those in healthy donor neutrophils. These results suggest that deficiency of CNL neutrophil function might be due to insufficiency of some inflammatory cytokine-specific signaling. Hence, we are the first to show that CNL neutrophils have partially insufficiency in some cytokine-specific signaling. Further studies are needed to elucidate the signal transduction pathways relating to functional defects in CNL neutrophils.     

Functional characterization of the cells in chronic neutrophilic leukemia

Light and electron microscopy of neutrophils from chronic neutrophilic leukemia (CNL) did not reveal differences from normal mature neutrophils. However, functional characterization of CNL cells showed marked differences when compared to normal cells. CNL neutrophils were much less viable in suboptimal conditions. Their survival was further reduced by autologous serum and was corrected by normal human serm. CNL cells showed very active phagocytosis, but their bactericidal activity was reduced in suboptimal conditions. The total content of lysozyme and β-glucuronidase was lower in CNL cells compared to normal neutrophils, but the release of these enzymes from stimulated cells was much higher than normal. This observation is compatible with a marked lysosomal lability. Cells from the patients' peripheral blood and bone marrow showed excessive growth in CFU-C assays. Marked susceptibility of CNL cells to cytotoxic activity of cold agglutinins, SLE sera, and CSFs was observed and may signify qualitative and/or quantitative differences in the membrane structure of CNL neutrophils, as compared to normal cells.