恶性血液病继发骨髓纤维化69例

目的探讨继发性骨髓纤维化（SMF）患者的临床及骨髓病理学特征。方法对69例SMF患者的临床表现、外周血涂片、骨髓涂片及骨髓活检情况进行回顾性分析,对不同疾病骨髓纤维化程度与巨核细胞数目进行相关性分析。结果69例SMF患者原发病分别为慢性粒细胞白血病（CML）20例（29．0％）,淋巴瘤14例（203％）,急性髓系白血病（AML）、骨髓增生异常综合征（MDS）各10例（14．5％）,急性淋巴细胞白血病（ALL）6例（8．7％）,多发性骨髓瘤（MM）4例（5．8％）,骨髓增殖性肿瘤（MPN）3例（4．3％）,慢性淋巴细胞白血病（CLL）2例（2．9％）。病理骨髓纤维化程度与巨核细胞数之间无相关性（r=0．024,P=0．848）。结论临床上多种血液系统疾病可以引起SMF。初诊的造血系统恶性疾病患者应同时行骨髓活检,特别是脾大、骨髓“干抽”的患者要考虑SMF的可能,骨髓病理学检查对临床诊断和鉴别诊断具有重要意义。     

骨髓活检与骨髓涂片同步分析对血液病诊断的探讨

 目的　探讨骨髓活检和骨髓涂片同步分析在血液病诊断中的意义。方法　对81例血液病患者,采用骨髓抽吸-活检一步法取材,行常规染色及网状纤维染色,观察增生程度、细胞形态等指标。结果　在再生障碍性贫血（AA）、急性白血病（AL）、骨髓转移癌（MCBM）、骨髓纤维化（MF）、骨髓增生异常综合征（MDS）、多发性骨髓瘤（MM）诊断方面的涂片诊断率分别为80 %、87 %、50 %、38 %、74 %、67 %,骨髓活检诊断符合率100 %、100 %、100 %、100 %、93 %、89 %,骨髓活检优于涂片（P＜0.05）;而白血病FAB分型及诊断,骨髓涂片优于活检 。结论　骨髓涂片和骨髓活检各具优缺点,互为补充,联合检查可以提高对血液病诊断的准确性。     

慢性粒细胞白血病骨髓网状纤维与巨核细胞增生的观察

目的　为了解慢性粒细胞白血病 (CML)骨髓中巨核细胞和网状纤维的增生情况及其关系。方法　观察33例CML患者的骨髓活检组织 (塑料包埋、HGF和Gomori染色 )的病理学改变。结果　发现所有患者的骨髓组织均存在网硬蛋白纤维增多 ,且随CML进展其程度加重 ;大多数患者巨核细胞过度增生 ,在CML不同阶段中巨核细胞数比较未见显著差异。结论　提示CML继发性的骨髓纤维组织增生主要与病情演进有关 ,并涉及巨核细胞的增生。     

14例骨髓增生异常综合征伴骨髓纤维化的病理与临床分析

 目的 探讨骨髓增生异常综合征伴骨髓纤维化（MDS-MF）的病理与临床特征。方法　采用骨髓穿刺涂片Wright染色光镜观察分类;骨髓活检组织塑料包埋切片,瑞特-吉姆萨染色光镜观察组织学变化及Gomory网状纤维染色,回顾性观察总结14例MDS-MF患者的临床表现、骨髓细胞学、骨髓组织学特征。结果　14例中RA 4例,RA-RS 3例,RAEB-Ⅰ3例,RAEB-Ⅱ4例。全血减少3例（21.4 %）,两系减低7例（50 %）,一系减低4例（28.6 %）,14例末稍血涂片均见幼粒、幼红细胞及泪滴状红细胞。骨髓涂片中增生减低／极度减低5例（35.7 %）、增生活跃／明显活跃9例（占64.3 %）。骨髓细胞发育不良100 %。巨核0 ~ 105个,7例缺如（占50 %）,3例有典型单圆及多圆核巨核细胞（占21.4 %）。骨髓组织增生低下仅占1例,增生极度活跃者6例。14例均可见骨髓胶原纤维增生和ALIP现象,原始细胞明显增多7例。网状纤维"+++"５例,"++++"９例。脾大4例,肝大1例,反复骨髓干抽5例。结论　MDS-MF是MDS的一种变型,必须结合外周血细胞形态,骨髓细胞发育不良表现、骨髓活检幼稚细胞增多、胶原纤维和网状纤维增生等特点诊断,并与伴有纤维化的其他相关疾病鉴别。     

淋巴浆细胞淋巴瘤／Waldenstr?觟m巨球蛋白血症的形态学诊断

  目的　提高对淋巴浆细胞淋巴瘤（LPL）／Waldenstr?觟m巨球蛋白血症的认识。方法　对1例LPL患者的诊治过程进行回顾性分析,并复习有关文献,对慢性淋巴细胞白血病、多发性骨髓瘤、脾边缘区淋巴瘤进行鉴别诊断。结果　患者血涂片淋巴细胞0.40,分类100个白细胞可见晚幼红1个,血小板少见,红细胞呈明显缗钱状排列。骨髓象：增生活跃,淋巴样细胞0.78,浆细胞0.085。骨髓活组织检查示：骨髓增生极度活跃,淋巴样细胞和浆样细胞弥漫性分布,形态学诊断为淋巴浆细胞淋巴瘤／Waldenstr?觟m巨球蛋白血症。结论　LPL与慢性淋巴细胞白血病、多发性骨髓瘤和伴外周血的脾淋巴瘤等疾病临床及实验室特征有相似之处,往往难以鉴别, 血涂片、骨髓涂片及骨髓组织学等形态改变在LPL诊断及鉴别诊断中能起到决定性作用。     

急性髓系白血病（非M3）化疗后骨髓油滴和巨核细胞数变化规律及其预后意义

 目的　探讨急性髓系白血病（AML）（非M3）患者化疗后骨髓油滴和巨核细胞数变化规律及其预后意义。方法　对99例初诊AML（非M3）患者资料进行回顾性分析,评价规范治疗各阶段骨髓油滴及巨核细胞数变化及其对总体生存（OS）率、无病生存（DFS）率的影响。结果　99例患者中位DFS为 21（2～88）个月,3年DFS率为47.3 %,中位OS 70（4～89）个月,3年OS率55.8 %。诱导化疗达完全缓解（CR）后骨髓油滴随着诱导缓解后化疗次数增加呈增加趋势,而巨核细胞数呈减少趋势。将单因素分析提示有意义的诱导缓解后第2次化疗后巨核细胞数变化率、诱导缓解后第1～3次化疗后骨髓油滴变化、骨髓纤维化分级、初诊乳酸脱氢酶值、白血病细胞免疫分型、起病时骨髓白血病细胞比例及诱导化疗结束后第7～10天残留白血病细胞比例等观察指标纳入多因素分析,结果提示起病时骨髓白血病细胞比例小于50 %、诱导缓解后第3次化疗后骨髓油滴较诱导化疗CR期增多对于延长患者DFS时间有独立预后意义（P＝0.010、0.018）;而诱导化疗结束后第7～10天残留白血病细胞比例≥10 %及诱导缓解后第2次化疗后骨髓巨核细胞数变化率≤-50 %为OS的独立不良预后因素（P＝0.009、0.038）。结论　AML（非M3）患者达CR后,随着诱导缓解后化疗次数增加骨髓油滴呈增加趋势,而巨核细胞数呈减少趋势。动态观察骨髓油滴及巨核细胞计数有助于患者预后判断。     

急性全髓增殖症伴骨髓纤维化研究进展

急性全髓增殖症伴骨髓纤维化（acute panmyelosis with myelofibrosis，APMF）是一种全髓细胞增生伴骨髓纤维增生的疾病。WHO关于造血和淋巴组织肿瘤分型中将其作为独立的亚型，与其他类型急性髓系白血病相比，该病发病率低，相关研究较少。其主要特点为全髓增生、明显骨髓纤维化、全血细胞减少、红细胞形态正常、脾不大、进展迅速等。治疗包括支持治疗：输血，糖皮质激素，生长因子和在原始细胞明显增多时和进展为明显的急性髓细胞白血病（acute myelocytic leukemia，AML）时应用骨髓抑制性药物、造血干细胞移植和双磷酸盐。     

骨髓纤维化74例临床分析

 目的 探讨骨髓纤维化（MF）的诊治方法,提高对该类疾病的认识。方法 回顾性分析1994年1月至2004年10月沈阳市红十字会医院74例MF患者的临床资料。结果 MF约占同期因血液系统异常行骨髓活检人数的1.86 %,病因依次为：慢性骨髓增生性疾病（CMPD）、原发性骨髓纤维化（IMF）、急性白血病（AL）、慢性肾功能不全及其他。结论 MF的主要病因为CMPD、IMF及慢性肾功能不全等内科疾病所致,凡疑为MF者必须进行骨髓活检确诊。     

慢性淋巴细胞白血病涂片与切片诊断价值的比较

目的:比较骨髓活检与涂片两种方法诊断慢性淋巴细胞白血病(CLL)的价值.方法:同步观察32例慢性淋巴细胞白血病患者骨髓涂片和活检切片,并与20例反应性淋巴细胞增多症患者作比较.观察骨髓增生程度、细胞形态学分类(髓内增生的优势细胞系)及组织病理学分类、纤维组织增生程度.结果:CLL组患者骨髓造血组织在切片中的增生度高于涂片,两者差异有统计学意义(P＜0.05);与反应性淋巴细胞增多症比较差异亦有统计学意义(P＜0.05).CLL组中根据瘤细胞的形态学差异,分为典型CLL、伴幼淋巴细胞CLL和大小细胞混合型CLL;按照组织病理学又分为结节型、间质型、弥漫型;4例涂片未能作明确诊断,切片比涂片敏感性高.CLL组网硬蛋白纤维积分为1+及以上占12.5%,反应性淋巴细胞增多症均为阴性或弱阳性反应,差异有统计学意义(均为P＜0.05).结论:切片除了在淋巴细胞形态上能够反映疾病的类型,还能在组织病理上反映浸润的模式与程度,常能提供附加的预后信息.在做传统的骨髓涂片检测时,应同时做骨髓活检,可以提供更准确丰富的诊断依据及信息.     

骨髓细胞学分类与骨髓活检相结合在全血减少疾病诊断中的意义

 目的 探讨骨髓穿刺涂片联合活检病理切片在全血细胞减少性血液疾病诊断中的临床应用 。方法 筛选同时进行骨髓穿刺涂片及活检的全血细胞减少性血液疾病患者328例,进行回顾性分析。结果 328例患者中男154例,女174例,年龄4-79岁。骨髓活检在再生障碍性贫血（AA）、骨髓增生异常综合症(MDS)、骨髓纤维化(MF)、等方面诊断符合率高于骨髓涂片,有统计学差异（P<0.05）,骨髓活检增生程度的判断优于骨髓涂片。 结论 骨髓穿刺涂片联合骨髓活检病理切片更能客观准确地反映骨髓的真实情况,特别是在恶性血液系统疾病所致全血细胞减少的诊断、鉴别诊断等方面的价值更优于涂片,二者联合检查可以进一步提高全血细胞减少性疾病诊断的准确性。 关键词 全血细胞减少 骨髓涂片 骨髓活检 病理     

Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia,high-risk myelodysplastic syndrome,and myeloproliferative disorders

BACKGROUND: Imatinib mesylate is a selective tyrosine kinase inhibitor of c-abl, bcr/abl, c-kit, and platelet-derived growth factor-receptor (PDGF-R). c-kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD). METHODS: The authors investigated the efficacy of imatinib in patients with these disorders. Forty-eight patients with AML (n = 10), MDS (n = 8), myelofibrosis (n = 18), atypical chronic myeloid leukemia (CML; n = 7), chronic myelomonocytic leukemia (CMML; n = 3), or polycythemia vera (n = 2) were treated with imatinib 400 mg daily. RESULTS: None of the patients with AML or MDS responded. Among patients with myelofibrosis, 10 of 14 patients with splenomegaly (71%) had a 30% or greater reduction in spleen size, 1 patient had trilineage hematologic improvement, 2 had erythroid hematologic improvement, and 1 had improvement in platelet count. One patient with atypical CML had erythroid hematologic improvement. Both patients with polycythemia vera needed fewer phlebotomies (from 2-3 per year to none during the 8 months of therapy and from 3-6 per year to 1 during 9 months of therapy). None of the three patients with CMML responded. Treatment was well tolerated. The side effects were similar to those observed in patients with CML. CONCLUSIONS: Within these small subgroups of disease types, single-agent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGF-R fusion genes. Preliminary data on polycythemia vera are promising and deserve further investigation. Responses among myelofibrosis patients were minor. Therefore, a combination treatment regimen including imatinib may be more effective.     

Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: Real-world data

The impact of ruxolitinib therapy on evolution to blast phase (BP) in patients with myelofibrosis (MF) is still uncertain. In 589 MF patients treated with ruxolitinib, we investigated incidence and risk factors for BP and we described outcome according to disease characteristics and treatment strategy. After a median follow-up from ruxolitinib start of 3 years (range 0.1-7.6), 65 (11%) patients transformed to BP during (93.8%) or after treatment. BP incidence rate was 3.7 per 100 patient-years, comparably in primary and secondary MF (PMF/SMF) but significantly lower in intermediate-1 risk patients (2.3 vs 5.6 per 100 patient-years in intermediate-2/high-risk patients, P < .001). In PMF and SMF cohorts, previous interferon therapy seemed to correlate with a lower probability of BP (HR 0.13, P = .001 and HR 0.22, P = .02, respectively). In SMF, also platelet count <150 × 10⁹/l (HR 2.4, P = .03) and peripheral blasts ≥3% (HR 3.3, P = .004) were significantly associated with higher risk of BP. High-risk category according to dynamic International Prognostic Score System (DIPSS) and myelofibrosis secondary to PV and ET Collaboration Prognostic Model (MYSEC-PM predicted BP in patients with PMF and SMF, respectively. Median survival after BP was 0.2 (95% CI: 0.1-0.3) years. Therapy for BP included hypomethylating agents (12.3%), induction chemotherapy (9.2%), allogeneic transplant (6.2%) or supportive care (72.3%). Patients treated with supportive therapy had a median survival of 6 weeks, while 73% of the few transplanted patients were alive at a median follow-up of 2 years. Progression to BP occurs in a significant fraction of ruxolitinib-treated patients and is associated with DIPSS and MYSEC-PM risk in PMF and SMF, respectively.     

慢性粒细胞白血病80例骨髓活检分析

目的:对慢性粒细胞白血病骨髓活检进行分析,以便全面了解慢性粒细胞白血病的骨髓情况,有助于诊断及治疗。方法:用塑料包埋法制片,然后进行HGF,Gomori染色,观察各项指标。结果:80例病人中78例(97％)骨髓增长明显活跃;19例(61％)伴有不同程度的纤维化;19例(23％)可见3～10个原幼细胞簇。结论:骨髓活检可以全面了解慢性粒细胞白血病的骨髓增生情况、骨髓纤维化程度及原幼细胞簇数量,对判断分期及预后,指导治疗有较重要的意义。     

Beyond chronic myelogenous leukemia: potential role for imatinib in Philadelphia-negative myeloproliferative disorders

The myeloproliferative disorders (MPDs) are chronic malignant conditions originating from the clonal expansion of a multipotential hematopoietic stem cell. These diseases include polycythemia vera (PV), essential thrombocythenia, atypical chronic myeloid leukemia, idiopathic hypereosinophilic syndrome (HES), agnogenic myeloid metaplasia with myelofibrosis, and others. Receptor tyrosine kinases-the platelet-derived growth factor receptors (PDGFRs) and c-Kit-and their respective ligands have been implicated in the pathogenesis of MPDs. For example, a constitutively activated PDGFR fusion tyrosine kinase (FIP1L1-PDGFRA) was identified in some patients with HES, a disease characterized by sustained overproduction of eosinophils that has been classified by the World Health Organization as a chronic subtype of the MPDs. Imatinib is a selective inhibitor of PDGFRs, c-Kit, Abl and Arg protein-tyrosine kinases, as well as Bcr-Abl, the oncogenic tyrosine kinase that causes chronic myeloid leukemia. The efficacy of imatinib in treating HES, systemic mast cell disease, chronic myelomonocytic leukemia associated with PDGFRbeta fusion genes, and (to a lesser extent) PV and idiopathic myelofibrosis was reviewed from institutional experience and a review of the literature. In 3 studies that involved 11 patients with PV, 10 patients had reductions in phlebotomy with imatinib. Eight studies of 42 patients with HES indicated that 70% achieved complete hematologic remissions with imatinib. Four studies of 6 patients with MPD indicated responses with imatinib in 5 patients. Insight into the molecular pathogenesis of MPDs will improve the definitions of different disease categories and suggests that signal transduction inhibition is likely to be an increasingly important treatment option in the future.     

慢性粒细胞白血病急性变36例临床分析

自１９７８年元月至１９９３年４月经血液学确诊的慢性粒细胞白血病急性变（简称慢位急变）患者３６例，其中急粒变者３３例占９１．６６％，急淋变２例，嗜碱性粒细胞变１例。从慢粒转为急变的病程为３个月～１４年，平均４６个月。从急变到死亡者平均６个月，最长者２年。对慢粒的预后因素、急变的前兆监测及治疗进行了讨论。     

CD34+/CD38- Stem Cell Burden Could Predict Chronic Myeloid Leukemia Patients’ Outcome

Background: The current predictor of the Chronic myeloid leukemia (CML)  patients’ outcome is the degree of response to targeted therapy; here we search for a biomarker predicting CML outcome before start of therapy. This study aimed to assess the impact of the  CD34+/CD38- stem cells (SCs) burden in chronic myeloid leukemia (CML) on  treatment response and patients’ outcomes. Methods: Our study included 65 CML patients in the chronic phase. The patients’  CD34+/CD38- stem cells were quantified  using flowcytometry before and after treatment by frontline imatinib (IM) therapy. The median follow-up for all patients was 18 months. Results: CD34+/CD38- stem cells frequency at diagnosis and after therapies are correlated to known prognostic markers (blast cells count, spleen size, total White cell count, and clinical scores). After therapy, the leukemic stem cells count dropped rapidly. The pretreatment CD34+/CD38- stem cells burden predicts response to frontline therapy. In addition, high SCs frequency at diagnosis predicts poor molecular response, transformation to AML, and poor patients’ outcomes. Conclusion: The percentage of CD34+/CD38- SCs burden at diagnosis reflects the CML disease behavior and is considered a biomarker for predicting CML patients’ response to first-line Tyrosine kinase inhibitors (TKI) therapy.     

STI571治疗慢性髓系白血病的临床疗效与毒副作用观察

背景与目的:bcr-abl融合基因翻译的蛋白产物P210bcr-abl的酪氨酸激酶(proteintyrosinekinase,PTK)活性异常增高被认为是导致慢性髓系白血病(chronicmyeloidleukmeia,CML)发病的根本原因。STI571能高效特异性抑制P210bcr-abl的PTK活性,在临床应用中获得了显著的疗效,但对急变期患者的治疗效果维持时间短。本研究观察和比较了STI571治疗慢性期与加速/急变期CML患者的临床疗效和所发生的不良反应,并从细胞遗传学的角度对急变期患者STI571耐药机制进行初步的分析。方法:选择接受STI571治疗的CML患者22例,其中慢性期6例,加速/急变期16例。按照血液学缓解和细胞遗传学缓解的标准,结合骨髓细胞形态学分析、骨髓细胞G显带技术分析和间期荧光原位杂交检测结果,对患者STI571治疗前和治疗3个月后的血液学和细胞遗传学缓解情况进行分析,并对3个月内出现耐药复发的患者进行核型演化分析。同时密切观察各系统发生的不良反应及严重程度。结果:6例(100%)慢性期CML患者获血液学完全缓解和细胞遗传学缓解,4例(25%)加速/急变期CML患者获血液学完全缓解,8例(50%)获不同程度的细胞遗传学反应。获血液学完全缓解和细胞遗传学反应的百分率两组比较均有统计学差异(P<0.05)。3例急变期CML患者出现耐药复发,其中2例可见2Ph和其它新     

活化诱导胞嘧啶核苷脱氨酶基因在白血病中的表达

目的：探讨活化诱导胞嘧啶核苷脱氨酶（AID）在急性白血病（AL）、慢性粒细胞白血病慢性期（CML-CP）和急变期（CML-BC）患者及白血病细胞株中的表达特点。方法采用实时定量反转录聚合酶链反应（RT-PCR）检测89例初诊急性淋巴细胞白血病（ALL）患者、79例初诊急性髓系白血病（AML）患者、5例 CML-BC 患者、5例 CML-CP 患者和白血病细胞株 NB4、THP-1、KG-1、Raji、K562中 AID mRNA 的表达,以16名健康供者骨髓单个核细胞作为对照。结果89例 ALL 患者和79例 AML 患者 AID mRNA的中位表达水平分别为3.785（0.006～7463.175）、1.812（0.005～69.107）,健康对照组 AID mRNA 的表达水平为1.483（0.146～4.707）。 ALL、B-ALL、伯基特型白血病、Raji 细胞株和 M4的 AID mRNA 表达水平较健康对照组升高,差异均有统计学意义（均 P＜0.05）,而 M3、NB4和 KG-1细胞株的 AID mRNA 表达水平较健康对照组下降,差异均有统计学意义（均 P＜0.05）。 K562细胞株的 AID mRNA 表达水平较 CML-CP患者升高,差异有统计学意义（P＜0.001）。 CML-BC、CML 淋系急性变（CML-LBC）和 CML 髓系急性变（CML-MBC）患者的 AID mRNA 表达水平也高于 CML-CP 患者。结论 AID 在 B-ALL、伯基特型白血病、M4中呈高水平,在 M3和 KG-1细胞株中呈低表达,在 CML-BC 中出现表达水平的显著升高。