慢性中性粒细胞白血病伴多发性骨髓瘤1例合并文献复习

目的 分析慢性中性粒细胞白血病(CNL)伴多发性骨髓瘤的临床病理特征.方法 回顾性分析1例CNL伴多发性骨髓瘤患者的临床病理资料,并结合相关文献,进行分析.结果 患者中性粒细胞显著上升,脾脏肿大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体及BCR/ABL融合基因,骨髓粒系有明确增生,未见病态造血和纤维化改变,排除类白血病反应等其他可能导致中性粒细胞增多的因素,合并多发性骨髓瘤.结论 CNL临床少见,其发病有一定特殊性,具体机制及干预方法需要进一步研究.     

慢性中性粒细胞白血病2例并文献复习

目的:研究对慢性中性粒细胞白血病(CNL)的特点.方法:报告2例CNL并结合文献进行复习.结果:患者中性粒细胞明显增多,脾大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体、bcr-abl融合基因,骨髓粒系增生,无病态造血和明显纤维化依据,排除了如类白血病反应、其他克隆性血液病引起的中性粒细胞增多,其中1例伴有单克隆免疫球蛋白血症,2.5年后转化为急性白血病.结论:CNL是一种少见的骨髓增殖性疾病,多发生于老年人,预后差,治疗无标准方案,年轻患者应进行异基因造血干细胞移植以达到治愈目的.     

WHO慢性骨髓增生性疾病的诊断

慢性骨髓增生性疾病(CMPD)为一组克隆性造血干细胞疾病,表现为骨髓髓系细胞(粒系、红系、巨核系)≥1系增生,分化成熟相对正常,引起外周血白细胞、红细胞和/或血小板增多.     

中药治疗慢性粒细胞白血病的研究进展

慢性粒细胞白血病（chronic myelocytic leukemia,CML）,也称作慢性髓系白血病,属于慢性白血病的1种常见亚型。CML是1种造血干细胞克隆性增殖所致的骨髓增殖性疾病,临床常简称慢粒。临床特征为进行性外周血白细胞增多,可见到各阶段的不成熟粒细胞,嗜碱及嗜酸性粒细胞增多,骨髓有核细胞极度增多,以粒细胞系为主,     

慢性中性粒细胞白血病2例并文献复习

目的：研究对慢性中性粒细胞白血病（CNL）的特点。方法：报告2例CNL并结合文献进行复习。结果;患者中性粒细胞明显增多,脾大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体、bcr-abl融合基因,骨髓粒系增生,无病态造血和明显纤维化依据,排除了如类白血病反应、其他克隆性血液病引起的中性粒细胞增多,其中1例伴有单克隆免疫球蛋白血症,2．5年后转化为急性白血病。结论;CNL是一种少见的骨髓增殖性疾病,多发生于老年人,预后差,治疗无标准方案,年轻患者应进行异基因造血干细胞移植以达到治愈目的。     

慢性中性粒细胞白血病4例临床分析

慢性中性粒细胞白血病（chronic neutrophilic leukemia，CNL）是一种少见的慢性白血病，临床上以成熟中性粒细胞持续增多、脾大为主要特征，目前尚无统一诊断标准，但近年WHO倾向于将其归类于慢性骨髓增殖性疾病，本文收集4例CNL进行分析如下。     

35例慢性粒-单核细胞白血病细胞形态学特征和染色体核型分析

 目的　进一步认识慢性粒-单核细胞白血病（CMML）细胞形态学和染色体核型特征。方法　回顾分析35例CMML患者的血象、骨髓象、细胞化学铁染色,18例染色体核型分析。结果　35例患者外周血白细胞（WBC）＞10.0×109／L 27例（87.3 %）,血红蛋白（Hb）浓度减低33例（94.3 %）,血小板（Plt）＜100×109／L 23例（65.7 %）。成熟单核细胞绝对值在（1.18～44.2）×109／L范围内。易见幼稚粒细胞者33例（94.3 %）,可见幼稚单核细胞者9例（25.7 %）。骨髓增生极度活跃或明显活跃28例（80 %）。分类中粒系+单核系≥0.70者20例（57.1 %）,可见幼稚单核细胞24例（68.6 %）。表现为一系或两系以上病态造血26例（74.3 %）。18例患者染色体核型分析,染色体异常5例（14.3 %）。结论　该组CMML的患者,血象以WBC增高、Hb和Plt同时减低明显增多为特点。易见幼稚粒细胞,单核细胞绝对值明显增高。骨髓增生异常综合征（MDS）伴单核细胞增多（MDS-CMML）的患者明显比具有骨髓增殖性疾病特征（MPD-CMML）的患者多见。CMML的患者染色体有核型异常,但无特异性,Ph染色体阴性。     

慢性中性粒细胞白血病

慢性中性粒细胞白血病(chronicneutrophilic leukemia,CNL)是一种少见类型的慢性白血病,临床上以成熟中性粒细胞持续增多,脾大为主要特征,1920年首先由Tuohy描述,以后国内外陆续有病例报道,有作者认为本病是慢性髓细胞白血病(CML)的一个亚型,1966年Rubin称之为CNL,随后的报道均沿用这一名称.     

伴粒、红、巨三系病态造血的初发性急性髓性白血病的临床与实验研究

伴粒、红、巨三系病态造血的初发性急性髓性白血病的临床与实验研究王学文，庄昱洲综述杨天楹审校初发性急性髓性白血病（ＡＭＬ）发病时无骨髓增生异常综合征（ＭＤＳ）作为前驱病变，亦非继发性白血病，初诊时骨髓白血病细胞之外的成熟细胞显示粒、红、巨核系三系有骨髓...     

慢性粒单细胞白血病伴嗜酸粒细胞增多1例报告

慢性粒单细胞白血病(CMML)已为我们熟知,自从WHO关于在造血与淋巴组织肿瘤分类方案中提出骨髓增生异常/骨髓增殖性疾病(MD/MPD)一词后,我们观察到CMML伴嗜酸粒细胞增多(CMML-EO)一例,现报道以求加深对此类疾病的理解。     

Atypical chronic myeloid leukemia as defined in the WHO classification is a JAK2 V617F negative neoplasm

Atypical chronic myeloid leukemia (aCML) as defined by the WHO classification is a rare hematopoietic stem cell disorder, which shows both myeloproliferative as well as myelodysplastic features. Because of the presence of neutrophilic leukocytosis, aCML may resemble chronic myelogenous leukemia. However, in contrast with the latter, aCML lacks a Philadelphia chromosome or the BCR/ABL fusion gene. The molecular pathogenesis of aCML and its relationship to other myeloproliferative neoplasms is unknown. To clarify these points, the presence of JAK2 V617F was examined by a retrospective analysis of archival specimens obtained from two large medical institutions.Paraffin-embedded bone marrow (BM) trephines and clot sections were examined by an allele-specific TaqMan PCR suitable for use with decalcified tissue. Fifty-nine cases of Philadelphia (Ph) chromosome negative chronic myeloproliferative neoplasms (CMPN) and normal bone marrows (BM) served as controls. None of the nine amplifiable cases of aCML and none of the normal BM controls showed a JAK2 V617F mutation, in contrast to 45/59 (76%) of the Ph chromosome negative CMPN cases. Atypical CML should therefore be considered as a JAK2 negative chronic myeloid neoplasm that remains properly categorized, alongside chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, within the WHO group of myelodysplastic/myeloproliferative neoplasms.     

Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia

Purpose of Review

We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients.

Recent Findings

Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases.

Summary

Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.

     

Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia

Background:Atypical chronic myeloid leukemia (aCML) is an infrequent chronic myeloproliferative disorder characterized by leukocytosis, absence of Philadelphia chromosome or BCR-ABL rearrangement, and marked myeloid dysplasia. Some cases have an absolute monocytosis but can be distinguished from chronic myelomonocytic leukemia (CMML) by the presence of a higher percentage (>15%) of circulating immature granulocytes. Patients and methods:In a series of 11 patients with a diagnosis of aCML according to the FAB proposals we have analyzed the most relevant clinical, hematological and cytogenetic characteristics. Results:The median age was 65 years (16–84). All but one case showed, at time of diagnosis, leukocytosis (median WBC was 36 × 10⁹/l), 55% had moderate anemia and 36% had thrombocytopenia. Most cases had marked dysplasia, particularly in the granulocytic lineage (82% of the cases), and all cases showed bone marrow red hypoplasia. Cytogenetic abnormalities were present in 9 out of the 11 patients. Trisomy 8 was observed in three cases and other clonal chromosomal abnormalities included deletions of 5q, 13q, 17p, 12q, and 11q as well as a t(6;8)(p23;q22) translocation. Fluorescence in situ hybridization (FISH) studies failed to demonstrate ETV-6 gene involvement. The median survival time from diagnosis was only 14 months (range 3–56 months). Conclusions:These data suggest that aCML is a rare disease which is characterized by leukocytosis, with dysgranulopoiesis, BM erythroid hypoplasia, chromosomal, though not recurrent, abnormalities and poor prognosis.     

骨髓增生异常综合征转化为不典型慢性髓性白血病--3例报告并文献复习

目的:报告3例骨髓增生异常综合征(MDS)转化为不典型慢性髓性白血病(aCML)。方法:比较该3例不同疾病阶段的临床表现、血象和骨髓涂片特征,并复习相关文献进行讨论。结果:本组3例患者均为老年,以慢性贫血起病,行骨髓检查分别诊断为MDS-RAS和MDS-RAEB,未用化疗;在随访中发现白细胞持续升高,以中性粒细胞为主,经骨髓和染色体等检查,诊断为aCML。结论:WHO分类系统将同时具有MDS和骨髓增殖症(MPD)特点的粒细胞疾病归为MDS/MPD,aCML是其中的一种亚型,由MDS自然转化为aCML的病例临床罕见。     

Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study.

This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged.     

Haematological differences between chronic granulocytic leukaemia, atypical chronic myeloid leukaemia, and chronic myelomonocytic leukaemia.

Chronic myeloid leukaemia (CML) is a generic term that include five apparently distinct entities. The best known form, the classical Ph-positive subtype, accounts for about 90% of all cases of CML. The morphology of its presentation blood film is highly characteristic but is also seen in about half of the remaining 10% of cases, which are Ph-negative. This classical morphological subtype, whether Ph-positive or Ph-negative I describe as 'chronic granulocytic leukaemia' to refer to the exuberant granulocytic proliferation which is its hallmark. This term is often used indiscriminately and interchangeably with 'chronic myeloid leukaemia' and similar terms, just as 'chronic lymphocytic leukaemia' was, until recently, used to cover the chronic lymphoid leukaemias in general, but is now used in a specific sense. Chronic granulocytic leukaemia (CGL), whether Ph-positive or Ph-negative, is almost always BCR-rearranged and associated with the production of a unique 210-kd protein with enhanced tyrosine kinase activity. Most of the remaining cases of Ph-negative CML are examples of either chronic myelomonocytic leukaemia (CMML), a subtype almost as homogeneous as CGL, and characterized in its presentation blood film by the presence of monocytes and neutrophils but few immature granulocytes, or atypical CML (aCML), distinct from and less homogeneous than either CGL or CMML, in which some cases also share features with CGL while others share some with CMML. CMML and aCML do not show BCR rearrangement and are not associated with the production of p210kd. CGL, CMML, and aCML, though characterized on morphological features differ in their clinical features and behaviour, response to treatment and survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性中性粒细胞白血病国内文献135例分析

 目的　总结国内慢性中性粒细胞白血病（CNL）的临床资料。方法　以"慢性中性粒细胞白血病"为主题词,检索中国知网（www. cnki. net）的中国期刊全文数据库（1994年至2008年）。结果　检索到CNL136例,男77例,女59例,男女比例1.305∶1,平均年龄57.8（8～87）岁。以头昏乏力、体检发现白细胞增高、上腹部不适或包块为主要症状,绝大多数脾大;外周血成熟中性粒细胞增高且持久,并以分叶核细胞为主,血清维生素B12及尿酸水平升高;骨髓增生明显或极度活跃,所有患者碱性磷酸酶（NAP）增高,Ph染色体和bcr-abl融合基因阴性。结论　CNL是罕见的一种慢性白血病,需与类白血病反应和慢性粒细胞白血病鉴别;CNL患者病程长短不一,有向急性白血病转化可能;目前以姑息治疗为主。     

Update on CML-Like Disorders

Chronic myeloid leukemia (CML) is defined for many years as BCR-ABL1 positive disease, but older publications refer to a poor prognosis, clinically heterogeneous entity termed ‘BCR-ABL1 negative CML’ constituting about 5% of CML cases. Apart from very rare CML cases with cytogenetically cryptic, atypical variant BCR-ABL1 fusions that had been inadvertently missed during the diagnostic work up, most of these cases would now be classified as a subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN), such as atypical CML (aCML), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL). A minority would be classified as systemic mastocytosis with associated hematological neoplasm (SM-AHN), myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or with PCM1-JAK2 (MLN-eo), or chronic eosinophilic leukemia not otherwise specified (CEL-NOS).¹     

Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases

Adult chronic myelomonocytic leukemia (CMML), as defined by the French-American-British (FAB) group, is associated with a variable survival, ranging from a few weeks to several years. From 1971 to 1986, we made the diagnosis of CMML in 107 cases, according to FAB criteria (except for patients with 20% to 30% bone marrow [BM] blasts who were also included). Median survival was 30 months (range 1 to 81 months) and life expectancy did not seem to be influenced by treatment modalities other than supportive care. Eighteen patients (17%) progressed to acute nonlymphoblastic leukemia (ANLL). In a Cox regression model, main factors associated with short survival were: an excess of marrow blasts (P = 10(-6], anemia (P = .17 x 10(-5], high peripheral blood (PB) monocytosis (P = .26 x 10(-5], presence of PB blasts (P = .49 x 10(-4], and to a lesser extent hyperleukocytosis (P = .001), presence of PB immature granulocytes, thrombopenia, and splenomegaly. Survival (less than 1 year v greater than 1 year) could be predicted at diagnosis in a multivariate stepwise discriminant analysis using two parameters only (percentage of BM blasts and hemoglobin level), with 82% accuracy. Among patients surviving greater than 1 year, initial PB leukocyte count was higher in patients with intermediate survival (12 to 42 months) than in long survivors (greater than 42 months) and was the only discriminating factor between these two subgroups in multivariate analysis. Abnormal cytogenetic findings and increased lysozymuria were also poor prognostic factors, but could not be analyzed in the multivariate models, as they were determined in a minority of patients. Parameters associated with subsequent progression to ANLL included younger age at diagnosis, thrombopenia, increased BM blasts, and splenomegaly. Our study allows for the identification of subgroups with different prognoses in CMML, on the basis of a small number of hematologic parameters, particularly initial percentage of BM blasts, hemoglobin level, and leukocytosis. These subgroups probably require different therapeutic approaches.