A review of perchloroethylene and rat mononuclear cell leukemia

Mononuclear cell leukemia (MNCL) is an extremely common spontaneous disease of ageing F344 rats accompanied by splenomegaly, anemia, thrombocytopenia, and leukemic infiltration (initially of the spleen, liver, and lung). Rare in other rat strains, incidence in F344 rats is variable, has been increasing, and can exceed 70% in controls. MNCL cells possess natural killer (NK) cell characteristics and apparently, the neoplastic cells derive from large granular lymphocytes (LGL), hence the alternative name of LGL leukemia. LGL leukemia is uncommon in man and occurs in two forms: T-LGL leukemia which has a chronic course, and the much rarer NK-LGL leukemia. In addition to cell type, the latter resembles F344 LGL leukemia being acute in course and involving more pronounced splenomegaly and thrombocytopenia. Chemically related increases in MNCL in F344 rats have not been associated with induction of human LGL leukemia. Carcinogenicity studies of perchloroethylene (PERC) in several rat strains have shown moderate, not clearly dose-related, increases in MNCL only in F344 rats (two studies). There was no consistent decrease in latency and the incidence in the PERC treated groups is within the overall control range. As a response in a rat strain highly predisposed to developing MNCL, these results are not considered predictive for human cancer risk.     

Erythrocyte superoxide dismutase in various hematological diseases

We measured superoxide scavenging activity (SSA) of erythrocytes with the recently developed chemiluminescence method by Nakano et al in Down syndrome and various hematological diseases. Hematological disorders were aplastic anemia, myelodysplastic syndrome, multiple myeloma, malignant lymphoma and chronic myelogenous leukemia. The SSA of erythrocytes was 1.7 times higher in Down syndrome, which was consistent with values reported in the previous publications. The erythrocyte SSA in patients of multiple myeloma treated with interferon-alpha was higher than that in healthy volunteers. The erythrocyte SSA in myelodysplastic syndrome, malignant lymphoma and chronic myelogenous leukemia did not differ from that in healthy volunteers. The mean value of erythrocyte SSA in aplastic anemia also remained within normal range. However, when an individual's hemoglobin concentration was compared with his or her own erythrocyte SSA, there was a clear correlation between them. Namely erythrocyte SSA increased when anemia was severe. There was no correlation between erythrocyte SOD activity and ageing.     

Clinical evaluation of biapenem for febrile neutropenia in patients with hematological disorders

We examined the clinical evaluation of biapenem (BIPM) for febrile neutropenia in patients with hematological disorders. BIPM was administrated by drip infusion when fever developed over 37.5 degrees C with a neutrophil counts lower than 1000/microl. The underlying diseases were acute myelogenous leukemia in 16 cases, acute lymphocytic leukemia in 1, malignant lymphoma in 14, myelodysplastic syndrome in 1, aplastic anemia in 1. Microbiologically documented infections were found in 3 cases (9.1%) before treatment. Clinical effect was excellent in 9 cases, good in 11, fair in 6, poor in 7. Factors associated with efficacy rate were concomitant use of granulocytecolony stimulating factor, duration of neutropenia and neutrophil counts at day 3 of day after start of the therapy. No serious adverse events were observed in all cases, although one case developed exanthema. In conclusion, these results confirmed the efficacy and safety of BIPM for febrile neutropenia in patients with hematological disorders.     

Low-dose cytarabine-induced hepatic and renal dysfunction in a patient with myelodysplastic syndrome.

We report a 49-year-old female patient with secondary myelodysplastic syndrome who developed liver dysfunction and acute renal failure caused by low-dose cytosine arabinoside (Ara-C) therapy. Treatment of low-dose Ara-C has widely been used for acute myelogeous leukemia and myelodysplastic syndrome, and it is thought to be a low toxicity except for myelosuppression. The patient complained of a transient adverse reaction in the second and third course of therapy. This rare case indicates that careful observation should be carried out during low-dose Ara-C therapy in view of allergic reactions.     

三氧化二砷联合LD-HA治疗MDS及难治性急性非淋巴细胞白血病的疗效观察

目的回顾性分析三氧化二砷联合LD-HA治疗MDS及难治性白血病的疗效及不良反应。方法应用三氧化二砷(10 mg/d,1⁵ d,85 d,8¹2 d)+LD-H A(高三尖杉酯碱2 mg/d,阿糖胞苷25 mg、2次/天,D112 d)+LD-H A(高三尖杉酯碱2 mg/d,阿糖胞苷25 mg、2次/天,D1¹4治疗。WBC<1.0×109/L时使用粒细胞集落刺激因子(G-CSF)5 g/(kg?d)直至WBC>1.0×109/L。结果 1个疗程的总有效率达67.5%,其中CR 24例(60%),PR 3例(7.5%),NR13例(32.5%)。复发难治AML和MDS患者1个疗程的CR率分别达45.5%(5/11)、65.5%(19/29)。结论三氧化二砷联合LD-HA能够有效的治疗MDS及难治性急性非淋巴细胞白血病。     

Large granular lymphocyte leukemia with pure red cell aplasia associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: an unfortuitous association?

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a recessively inherited monogenic disease caused by a mutation in the autoimmune regulator (AIRE) gene. AIRE plays a major role in central (thymic) immune tolerance. In the absence of AIRE, autoimmunity develops that is especially targeted at endocrine tissues. T-cell large granular lymphocyte (T-LGL) leukemia is a monoclonal lymphoproliferative disease characterized by persistent and indolent lymphocytosis. Autoimmune manifestations, such as rheumatoid arthritis or autoimmune cytopenia, are also common. We report the case of a patient with APECED, who presented with pure red cell aplasia associated with T-LGL leukemia. The association of T-LGL leukemia and APECED is very rare and may not be fortuitous. The immunological mechanisms of this association are discussed.     

Darbepoetin alfa: an effective treatment with flexible and simplified dosing for anemia in patients with cancer

Anemia is common in patients with cancer or myelodysplastic syndrome. Erythropoietic therapy offers an effective way to manage anemia by increasing hemoglobin levels, decreasing transfusion requirements, and alleviating symptoms. We reviewed data showing the feasibility and effectiveness of treatment with the erythropoiesis-stimulating protein darbepoetin alfa at extended dosing intervals to treat anemia in patients with cancer receiving multicycle chemotherapy. We also explored the darbepoetin alfa's potential for treating anemia in patients with myelodysplastic syndrome. Data from clinical studies and drug therapy evaluations confirm that darbepoetin alfa administered weekly, every 2 weeks, and every 3 weeks corrects and maintains hemoglobin levels in patients with chemotherapy-induced anemia. In addition, the data demonstrate that both weight-based and fixed dosing with darbepoetin alfa are effective, and that early intervention to treat anemia has clinical benefits. Darbepoetin alfa also is an effective treatment for anemia in patients with cancer not receiving chemotherapy, at extended dosing intervals of at least 3 weeks. Extended dosing for anemia treatment can provide benefits for patients, caregivers, and clinicians because it reduces the number of clinic visits needed and permits synchronizing anemia treatment with chemotherapy cycles. Data from recent studies suggest that darbepoetin alfa is effective for treating anemia in patients with myelodysplastic syndrome; this potential use is being investigated further in ongoing studies. Thus, darbepoetin alfa is an attractive therapy option for patients with chemotherapy or cancer-induced anemia. It allows increased flexibility and simplified dosing and may offer some benefit in the treatment of anemia in patients with myelodysplastic syndrome.     

141例全血细胞减少症患者病因分析

目的：探讨全血细胞减少的临床病因。方法：对141例全血细胞减少患者的临床资料进行回顾性分析。结果：141例中140例查明病因,1例不明。血液病为主要病因,占75.2%,非血液病占24.1%。各疾病按所占比例排序前5位依次为巨幼细胞性贫血、急性白血病、再生障碍性贫血、肝硬化脾功能亢进症、骨髓增生异常综合征。血液系统全血细胞减少病因以恶性及难治性疾病为主。结论：全血细胞减少病因复杂多样,除造血系统疾病外,需排除非造血系统疾病,以免误诊、漏诊。     

Report of a case with chronic myelomonocytic leukemia: demonstration of leukemic monocytes lacking nonspecific esterase by flow cytometry using monoclonal antibodies

Chronic myelomonocytic leukemia (CMML) is a rare leukemia, which is now included in myelodysplastic syndromes. In a small number of patients with CMML, problems in the diagnosis have been reported, especially when atypical morphological features in both monocytic and granulocytic cells due to dysmyelopoiesis are prominent, or when cytochemical characteristics are lost in the leukemic cells. The case history of a sixty-seven year-old male patient with CMML is described. The diagnosis of CMML in the patient was supported by the following evidence: chronic course of his disease; increased monocyte-like cells without other cause; normocytic anemia; immature granulocytic cells with hypogranular feature and giant platelets were observed in the peripheral blood. The bone marrow showed myeloid hyperplasia. Serum muramidase and vitamin B12 levels were increased, while neutrophil alkaline phosphatase score was low in the peripheral blood. Ph' chromosome was negative. The monocyte-like cells completely lacked nonspecific esterase. However the cells were confirmed as monocytic cells by flow cytometry using monoclonal antibodies to monocytes (OKM5).     

Interferon-alpha-induced pure red cell aplasia following chronic myelogenous leukemia

We report a case of pure red cell aplasia (PRCA) that resulted from interferon (IFN)-alpha therapy for chronic myelogenous leukemia. PRCA improved within 1 month after IFN-alpha was discontinued. This case indicates the involvement of IFN-alpha in the pathogenesis of PRCA.     

以发热为首发症状的儿童原发性髓系肉瘤1例报道并文献复习

髓系肉瘤(myeloid sarcoma,MS)是由髓系原始细胞或未成熟髓系细胞在髓外增生和浸润所形成的肿块,常伴随急性髓系白血病(AML)出现,也可出现于骨髓增殖性疾病(MPD)或骨髓增生异常综合征(MDS) 患者病程中,罕见于AML发生之前。外周血和骨髓均无白血病表现,称为原发性MS。MS 可出现在不同组织或器官中,可发生在任何年龄,但多见于青年和儿童,男性多于女性。MS临床表现无特异性,诊断比较困难,误诊率较高。笔者现报告l例以发热为首发症状的原发性MS 患儿,探讨其临床及实验室检查特点,并复习相关文献,以提高临床对MS的认识     

异基因造血干细胞移植治疗儿童血液病

目的探讨异基因造血干细胞移植治疗儿童血液病的价值。方法采用异基因造血干细胞移植治疗11例儿童血液病，其中再生障碍性贫血2例、白血病7例、骨髓异常增生症1例、非霍奇金淋巴瘤1例；预处理采用氟达拉滨／环磷酰胺（FLU／CTX）或全身放疗／环磷酰胺（TBI／CTX），观察患儿的临床治疗效果。结果10例患儿均移植成功，9例患儿生存，其中7例无病存活，存活最长时间为5．5年；CMV感染3例，继发出血性膀胱炎1例，继发弥漫性GVHD1例。结论异基因造血干细胞移植是治疗儿童血液病的有效方法，值得临床进一步推广。     

Therapeutic effects of a combination treatment with cefmetazole and netilmicin against infections complicated with hematological disorders

The efficacy and safety of a combination regimen using cefmetazole (CMZ) and netilmicin (NTL) were evaluated in the treatment of infections complicated with hematological disorders. Primary diseases in 31 patients included in the evaluation were acute myelocytic leukemia (3 cases), acute lymphocytic leukemia (2 cases), malignant lymphoma (14 cases), chronic myelocytic leukemia (2 cases), chronic myelocytic leukemia blast crisis (4 cases), myelodysplastic syndrome (2 cases), aplastic anemia (3 cases), and malignant histiocytosis (1 case). Complicated infections included 29 cases of suspected septicemia, 1 case of septicemia and 1 case of pneumonia. Clinical responses were excellent in 6 (19.4%), good in 12 (38.7%), fair in 1 (3.2%) and poor in 12 (38.7%). The total clinical efficacy rate was 58.1%. No significant effect of initial neutrophil counts was observed on response rates. Patients who showed increasing neutrophil counts during therapy had higher response rates than those in whom the neutrophil count decreased or remained unchanged at levels less than 500/mm3 in after neutrophil counts. No side effects were observed in any of the 31 patients. In conclusion, this combination therapy of CMZ and NTL thus appears to be useful and safe in therapies for infections complicated with hematological disorders.     

Zidovudine-induced reversible pure red cell aplasia

Hematological abnormalities are frequent among human immunodeficiency virus (HIV)-infected patients and may be directly attributable to the virus or may be caused by opportunistic infections, neoplasms or drugs that cause bone marrow suppression or hemolysis. Pure red cell aplasia (PRCA) is an uncommon hematological disorder that causes anemia. We report a 37-year-old male with HIV infection who developed PRCA 6 weeks after commencing Zidovudine and recovered following cessation of the drug. This is the first case of Zidovudine-induced PRCA reported from the Indian subcontinent.     

A case of acquired aplastic anemia with repeated cerebral infarctions at the beginning of immunosuppressive therapy

Acquired aplastic anemia is a rare hematopoietic stem-cell disorder that results in pancytopenia and hypocellular bone marrow. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. Acquired aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy such as antithymocyte globulin or cyclosporine. We present a rare case report of a 68-year old patient with acquired severe aplastic anemia with repeated cerebral infarctions at the beginning of immunosuppressive therapy. He started immunosuppressive drug therapy with antithymocyte globulin and cyclosporine. During follow-up, magnetic resonance imaging revealed high signals at right thalamus and right pons by diffusion-weighted image. He was diagnosed with repeated cerebral infarctions of right thalamus and right pons. We successfully managed cerebral infarctions by frequent transfusions, edaravone administration, keeping the trough of serum cyclosporine (CsA) concentration around lower limit. This is the first report of successful management of acquired aplastic anemia with repeated cerebral infarctions.     

凋亡抑制基因在急性白血病及骨髓增生异常综合征中的研究

目的探讨急性白血病及骨髓增生异常综合征患者骨髓凋亡抑制基因MCL-1、livin、aven的表达及临床意义。方法选取2012年9月~2013年12月本院收治的113例初发急性白血病患者,32例骨髓增生异常综合征患者及20例对照组患者（缺铁性贫血12例、血小板减少性紫癜8例）的新鲜骨髓液标本,采用RT-PCR方法检测MCL-1、livin、aven基因mRNA的表达水平及表达率。结果 AL组和MDS组MCL-1、livin、aven mRNA表达水平及阳性表达率分别高于对照组,差异有统计学意义（P〈0.05）。MCL-1与livin基因mRNA的表达呈正相关（r=0.586,P〈0.05）,MCL-1与aven基因的表达呈正相关（r=0.603,P〈0.05）,liven基因与aven基因表达无相关性（r=0,P〉0.05）。结论 3种凋亡抑制基因MCL-1、livin、aven基因mRNA在急性白血病及骨髓增生异常综合征中表达均增高。     

全血细胞减少610例临床分析

目的探讨全血细胞减少疾病的分类与发病机理。方法对610例全血细胞减少的患者进行外周血常规、骨髓象及相关检查。结果引起全血细胞减少的疾病很多,如：再生障碍性贫血（CAA）、低增生性白血病（HAL）、巨幼细胞性贫血（MA）、骨髓增生异常综合症（MDS）、脾功能亢进（脾亢）和免疫相关性疾病等。结论引起全血细胞减少的疾病很多,不仅仅是再障。     

Anti-erythropoietin and anti-thrombopoietin antibodies induced after administration of recombinant human erythropoietin

Recombinant human erythropoietin (rhEPO) has been successfully used for correcting renal anemia. However, recent studies have raised some concerns about the safety of rhEPO treatment due to its immunogenic side effect — pure red cell aplasia (PRCA). We now report a case of development of anti-EPO neutralizing antibodies (Abs) implicated in thrombocytopenia as well as erythrocytopenia. A 35-year-old man had a history of administering rhEPO (epoetin alfa, epoetin beta and darbepoetin alfa) for 2 years to treat renal anemia. The hematological parameters were collected. Anti-EPO, anti-platelet, and anti-thrombopoietin (TPO) Ab assays were performed to test the presence of autoreactive Abs. After performing antibody assays due to severe resistance to rhEPO treatment, a high titer of anti-EPO neutralizing Abs was detected. However, unexpectedly, this patient also showed thrombocytopenia rather than PRCA. We investigated the cause of the marked thrombocytopenia and found anti-TPO Abs in patient serum. To our best knowledge, this is the first report of the development of anti-TPO Abs during rhEPO treatment for anemia.     

Anti-erythropoietin and anti-thrombopoietin antibodies induced after administration of recombinant human erythropoietin

Recombinant human erythropoietin (rhEPO) has been successfully used for correcting renal anemia. However, recent studies have raised some concerns about the safety of rhEPO treatment due to its immunogenic side effect — pure red cell aplasia (PRCA). We now report a case of development of anti-EPO neutralizing antibodies (Abs) implicated in thrombocytopenia as well as erythrocytopenia. A 35-year-old man had a history of administering rhEPO (epoetin alfa, epoetin beta and darbepoetin alfa) for 2 years to treat renal anemia. The hematological parameters were collected. Anti-EPO, anti-platelet, and anti-thrombopoietin (TPO) Ab assays were performed to test the presence of autoreactive Abs. After performing antibody assays due to severe resistance to rhEPO treatment, a high titer of anti-EPO neutralizing Abs was detected. However, unexpectedly, this patient also showed thrombocytopenia rather than PRCA. We investigated the cause of the marked thrombocytopenia and found anti-TPO Abs in patient serum. To our best knowledge, this is the first report of the development of anti-TPO Abs during rhEPO treatment for anemia.     

超小剂量地西他滨治疗骨髓增生异常综合征和急性髓系白血病11例疗效观察

目的 分析超小剂量地西他滨治疗骨髓增生异常综合征(MDS)和急性髓系白血病(AML)的近期临床疗效和不良反应.方法 观察11例接受超小剂量地西他滨治疗的患者临床疗效和不良反应发生率.其中,6例中危-Ⅰ组MDS患者接受地西他滨5~7 mg· m-2· d-1,连用5~6 d的超小剂量方案;2例中危-Ⅱ组和1例高危组MDS患者接受地西他滨联合半程CAG治疗方案;1例高危组MDS患者接受地西他滨联合HA治疗方案;1例AML患者接受地西他滨联合DA治疗方案.结果 11例接受地西他滨治疗的患者中,3例完全缓解,4例部分缓解,1例血液学改善,2例疾病无进展,1例死亡.总有效率为72.7%,完全缓解率为27.3%.3例患者出现肺部感染,1例出现消化道出血.3例出现Ⅱ级血液学不良反应,3例出现Ⅲ级血液学不良反应,均治疗后好转.结论 超小剂量地西他滨治疗方案在中高危组MDS患者中安全有效,耐受性好,且感染及血液学不良反应发生率较低,可在临床进一步推广.