Hepatitis-associated aplastic anemia with systemic plasmacytosis

An autopsy case of hepatitis associated aplastic anemia was presented. A 58-year-old Japanese female with non-A, non-B hepatitis was admitted on August 2, 1983. Moderate grade of fever and hemorrhagic diathesis appeared on September 16, when hepatitis was evaluated as being under resolving. The peripheral blood and bone marrow findings were consistent with aplastic anemia. Since infection was suggested by increased levels of serum gammaglobulin and CRP, treatment with antibiotics as well as prednisolone and blood transfusion was initiated. Since September 21, gradual tenderness and edema on the right lower abdominal wall appeared. She died on October 3. On postmortem examination, systemic plasmacytosis with lymphadenopathy and septic monilial infection was revealed. Numerous plasma cells were atypical, but were immunohistochemically proved to be polyclonal. The bone marrow showed a massive and diffuse plasma cell proliferation with extremely scarce myeloid cells and megakaryocytes. There was a large granulomatous lesion with monilial infection in the wall of the ileocecum. By these findings, systemic plasmacytosis was suspected to be due to chronic monilial infection. The pathogenesis of systemic plasmacytosis in aplastic anemias and in other diseases were discussed with relation to the present case.     

病毒性肝炎合并再生障碍性贫血的临床研究

目的 研究病毒性肝炎合并再生障碍性贫血的临床特征,探讨这类疾病的临床转归及治疗方法。方法 对2004年4月至2009年9月在地坛医院住院诊断为病毒性肝炎并且合并再生障碍性贫血的25例患者进行回顾性分析,本组病例中再生障碍性贫血诊断均通过骨穿确诊,收集患者的临床资料,包括肝病病史、药物过敏史、住院期间用药史、生化检查等等,对其进行描述性分析。结果 25例病毒性肝炎患者在经组织病理学诊断同时合并再生障碍性贫血,其中17例为男性,8例为女性;12例为慢性乙型肝炎患者,4例为慢性丙型肝炎患者,l例为急性戊型肝炎患者,l例为巨细胞病毒感染所致肝炎,7例为未分型病毒性肝炎患者,7例诊断为重型肝炎;仅有3例患者在入院前有干扰素短期使用史,其余患者未使用影响血象药物;治疗过程中使用集落细胞细胞刺激因子者6例,使用丙种球蛋白者9例,使用糖皮质激素者3例,使用促红素者1例,仅用口服药物升血细胞治疗者2例,输红细胞者6例,输血小板者2例;好转出院者20例,自动出院者3例,因重型肝炎其他合并症死亡者2例。结论 病毒性肝炎合并再生障碍性贫血的治疗以治疗原发性肝病及核苷类似物抗病毒治疗为主,血液病方面对症支持治疗,随肝病好转血液病逐渐同时恢复,预后较好。     

Hepatitis-associated aplastic anemia: description of a new case

Hepatitis-associated aplastic anemia is an only recently recognised syndrome. We present a case whereby a month after an episode of fever, a 17-year-old boy was recovered with liver enzyme elevation and circulating platelet reduction. All the acute viral hepatitis markers were negative. After bone marrow aspiration a severe aplastic anemia was diagnosed and all the findings were consistent with hepatitis-associated aplastic anemia. The disorder was initially treated with glucocorticoids and platelet transfusion, obtaining the normalization of the liver enzymes but worsening of the aplastic anemia. An HLA-identical related marrow donor was not found. The patient responded to immunosuppressive treatment but died of multi-organ failure due to severe sepsis.     

A study of bone marrow failure syndrome in children

Background: Bone marrow failure syndrome (BMFS), or aplastic anemia, includes peripheral blood single cytopenias, as well as pancytopenia due to inability of the marrow to effectively produce blood cells. Aim: To study the clinico-hematological profile and etiological factors of bone marrow failure syndrome in children. Setting and Design: This prospective study was carried out in the Department of Pediatrics of a university teaching hospital over 36 months. Materials and Methods: Children with pancytopenia (Hb 9 /L, platelet count < 100 x 10 9 /L) and bone marrow cellularity < 25% were included in the study. History of exposure to drugs, socioeconomic status, ethnicity and occupation of father were noted. Bone marrow aspiration; trephine biopsy; Ham test; viral studies for hepatitis A, B and C; and cytogenetic investigations were carried out. Statistical Analysis: Relative risk was estimated by odds ratio (OR) with 95% confidence interval (CI) in matched cases and controls. Results: Of the 53 children studied, 6 (11.3%) were diagnosed as Fanconi anemia. Two cases had features of myelodysplastic syndrome. Forty-five children were labeled as acquired aplastic anemia, of whom one had evidence of hepatitis B infection and two patients (5.8%) had paroxysmal nocturnal hemoglobinuria. Aplastic anemia was more common in children from family with lower socioeconomic status; in Muslims; and where the father's occupation was weaving, dyeing and painting. However, the number was small to make statistically significant conclusions. No correlation could be established with exposure to drugs. Conclusion: Fanconi anemia was responsible for approximately one-tenth of the cases of bone marrow failure syndrome. Majority of the patients had acquired aplastic anemia. Hepatitis B infection was an uncommon cause of acquired aplastic anemia.     

Spontaneous clinical and cytogenetic remission of aplastic anemia in a patient with del(13q)

We describe the case of a 64-year-old Japanese man with pancytopenia. Bone marrow biopsy findings were consistent with aplastic anemia. The patient was treated by transfusions without immunosuppressive therapy. Chromosome analysis of bone marrow cells at 6 months after onset showed a 46,XY,del(13) (q14q22) karyotype. The pancytopenia resolved gradually over the next 5 years; chromosome analysis of bone marrow cells at that time yielded normal findings. To our knowledge, this is the first report of spontaneous hematologic and cytogenetic remission of aplastic anemia. These findings suggest that the abnormal clone with deletion of the long arm of chromosome 13 was not sufficient for clonal evolution in aplastic anemia in this case.     

Indirect evidence of TTV replication in bone marrow cells, but not in hepatocytes, of a subacute hepatitis/aplastic anemia patient

The presence of a new DNA virus (TTV) has been reported in sera from patients with posttransfusion hepatitis of unknown etiology. The precise replication site of TTV, however, has not been established. In this study, the presence of TTV in liver autopsy material, and in bone marrow biopsy and autopsy samples taken from a subacute hepatitis/aplastic anemia patient was determined by PCR and Southern blot analyses. Liver cells were found to contain only TTV DNA and not mRNA. Bone marrow material, especially that taken at biopsy, contained high levels of TTV DNA. It is suggested that the TTV replication site was in the bone marrow rather than in the liver, and that TTV infection was the cause of this patient's aplastic anemia. The precise etiological association of TTV with hepatitis remains to be established.     

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease In the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypo-plastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.     

荧光定量聚合酶链反应检测GATA-1、GATA-2、过氧化物酶体增殖物激活受体γ和干细胞因子基因在再生障碍性贫血患者及正常人骨髓间充质干细胞中的表达

背景：GATA-1、GATA-2、过氧化物酶体增殖物激活受体γ和干细胞因子基因在骨髓造血及成脂调控机制中起重要作用。 目的：观察GATA-1、GATA-2、过氧化物酶体增殖物激活受体γ和干细胞因子基因在再生障碍性贫血患者及正常人间充质干细胞中的表达。 方法：收集6例再生障碍性贫血患者及6位正常人骨髓液各10 mL,Ficoll贴壁法分离培养骨髓单个核细胞,达70%~80%融合后扩增传代。取传至第3代的间充质干细胞,应用流式细胞仪进行鉴定。提取总RNA,比较各组基因与内参基因之间的差别。荧光定量聚合酶链反应检测GATA-1、GATA-2、过氧化物酶体增殖物激活受体γ和干细胞因子基因在再生障碍性贫血患者及正常人间充质干细胞中的表达量。 结果与结论：与正常人间充质干细胞相比,再生障碍性贫血患者间充质干细胞的GATA-2和干细胞因子基因表达量降低(P=0.012,0.039),过氧化物酶体增殖物激活受体γ基因表达量升高(P=0.035);两组GATA-1基因表达量差异无显著性意义。提示GATA-2、干细胞因子基因的异常表达可能影响AA患者骨髓微环境的造血调控作用;过氧化物酶体增殖物激活受体γ基因的异常表达可能解释再生障碍性贫血患者骨髓易成脂的原因。     

Systemic polyclonal B-immunoblastic proliferation with marked peripheral blood and bone marrow plasmacytosis.

The clinical and pathologic features of a case of acute systemic polyclonal B-immunoblastic proliferation characterized by pronounced peripheral blood and bone marrow plasmacytosis and infiltration of the hepatic portal areas by immunoblasts, plasma cells, and lymphocytes are reported. Clinical and laboratory findings during the acute phase and long-term follow-up support the diagnosis of a benign process, possibly related to Pseudomonas aeruginosa septicemia. The patient experienced a dramatic clinical recovery on administration of high-dose intravenous corticosteroids. Pathologists should be aware of this entity so as not to confuse it with non-Hodgkin's lymphoma or a form of plasma cell dyscrasia.     

Peripheral blood and bone marrow findings in patients with acquired immune deficiency syndrome

In 4 years (1984-1987), 183 bone marrow examinations were performed on 155 human immunodeficiency virus (HIV) antibody positive patients. One hundred and fifty three had category IV AIDS. One-third of the marrows yielded specific information. This included opportunistic infection, in particular Mycobacterium Avium Intracellulare Complex (MAI) (24%), malignancy (4%), consistent with ITP (9%) and iron deficiency (1%). In the remaining two thirds of the bone marrows the most frequent non-specific abnormalities were dyserythropoiesis, erythroid hypoplasia, reticuloendothelial iron block, granulomas, lymphoid aggregates, plasmacytosis and histiocytosis. Common peripheral blood findings were anemia, lymphopenia, anisocytosis, rouleaux and atypical lymphocytes. Peripheral blood and bone marrow examinations on 16 patients on AZT are included. These patients have more pronounced blood and bone marrow abnormalities. The causes of these abnormalities are multifactorial and include low T4 levels, severe viral and other infections and therapy with marrow toxic drugs.     

骨髓间充质干细胞对再生障碍性贫血患者T细胞的免疫抑制

背景：骨髓间充质干细胞对再生障碍性贫血患者T细胞增殖的影响国内报道较少,而骨髓间充质干细胞是否通过抑制T细胞增殖实现对再生障碍性贫血患者的免疫调节目前尚无定论。 目的：观察人骨髓间充质干细胞对再生障碍性贫血患者T细胞的免疫调节作用。 方法：体外分离培养、扩增人骨髓间充质干细胞并通过形态学特征以及流式细胞术进行表面标志鉴定,将骨髓间充质干细胞分别与正常人和再生障碍性贫血患者外周血提取的T淋巴细胞共培养7 d。应用ELISA法检测各培养上清液中T淋巴细胞分泌的白细胞介素2、γ-干扰素、白细胞介素4及白细胞介素10水平。 结果与结论：再生障碍性贫血组患者培养上清液中T淋巴细胞分泌的白细胞介素2、γ-干扰素水平明显高于正常人(P < 0.05),白细胞介素4、白细胞介素10低于正常人(P < 0.05)。骨髓间充质干细胞可下调白细胞介素2、γ-干扰素表达,同时上调白细胞介素4、白细胞介素10表达,从而调节再生障碍性贫血患者的免疫紊乱。     

Haematological changes in HIV infection

HIV infection is associated with a wide range of hematological abnormalities. The peripheral blood findings and the morphological abnormalities in the bone marrow can simulate myelodysplastic syndrome, myeloproliferative disorders, and T cell lymphoma. We studied the peripheral blood smear and bone marrow findings of 42 patients with HIV infection over a 3-year period with the aim of recognising the morphological findings sufficiently characteristic of HV infection. The salient peripheral blood smear findilngs were anemia, bicytopenia and pancytopenia. The bone marrow revealed trilineage dysplasia, plasma cells and eosinophils, increased megakaryocytes, increased iron and reticulin fibrosis. In two cases the bone marrow revealed granulomata.     

真性红细胞增多症患者骨髓单个核细胞植入再生障碍性贫血小鼠

背景：真性红细胞增多症患者骨髓的高增殖低凋亡特性使其造血干细胞植入NOD/SCID小鼠后成功分化出粒红系细胞,但其能否植入并改善再生障碍性贫血小鼠造血功能,目前国内外尚未有报道。 目的：探讨JAK2阳性真性红细胞增多症患者骨髓单个核细胞植入后对再生障碍性贫血小鼠造血重建的影响。 方法：应用注射用重组人γ-干扰素联合白消安的方法建立再生障碍性贫血小鼠模型,随机分为实验组(n=10)和对照组(n=10),给药结束后第5天实验组经尾静脉输注真性红细胞增多症患者骨髓单个核细胞悬液,对照组同法输注等容积生理盐水。输注后第14天检测小鼠外周血常规、骨髓细胞形态、骨髓组织病理变化以及小鼠外周血和骨髓内CD45+细胞的百分含量。 结果与结论：输注后第14天,实验组小鼠血细胞计数三系减少,骨髓涂片可见散在淋巴细胞和早期造血细胞,骨髓组织活检可见骨髓增生减低,少量粒系细胞及幼红细胞,未见巨核细胞,与对照组比较,造血功能无明显改善。对照组小鼠外周血及骨髓均未检测到CD45+细胞,实验组小鼠外周血及骨髓均可检测到人源化的CD45+细胞,且骨髓中CD45+细胞比外周血高,提示JAK2V617F阳性真性红细胞增多症患者骨髓单个核细胞能成功植入再生障碍性贫血小鼠体内,但血常规、骨髓涂片及活检结果显示未能明显改善骨髓造血功能。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Bone marrow findings in lupus patients with pancytopenia

The marrow findings of 23 lupus patients with pancytopenia were reported. The most common findings were dyserythropoiesis and hypoplasia, both occurring in 9/23 (39%) of the cases. Neither feature was definitely related to cytotoxic drug therapy since most cases were treated by steroids only. Three of the hypoplastic marrows also showed gelatinous transformation, a condition characterized by disruption of marrow architecture, fat atrophy, and deposition of hyaluronic acid. Another common finding was lymphocytosis which occurred in 5/23 (22%) of the cases, 2 of which also had associated plasmacytosis. Two cases were associated with hyperplastic marrow, indicating peripheral destruction of blood cells and compensatory marrow hyperplasia. Reports in the literature on bone marrows in systemic lupus erythematosus are conflicting, describing mainly hypoplasia, vasculitis, plasmacytosis, red cell aplasia, and myelofibrosis. In our series, we found hypoplasia and lymphocytosis/plasmacytosis; in addition we described findings previously unreported: gelatinous transformation, dyserythropoiesis, and marrow hyperplasia.     

Aplastic crisis due to human parvovirus B19 infection in glucose-6-phosphate dehydrogenase deficiency

Human parvovirus B19 is known to cause aplastic crisis in patients with hemolytic anemias due to cytotoxic effect of the infection to erythroid progenitor cells. We report here the first case of aplastic crisis by B19 in a patient with glucose-6-phosphate dehydrogenase deficiency. A five-year-old boy was admitted to the hospital because of severe anemia, fever and jaundice. Four weeks after admission, he developed erythema infectiosum. B19 infection was confirmed using countercurrent immunoelectrophoresis, Southern blotting and hybridization method, and radioimmunoassay for B19 specific IgM. B19 virus antigen was detected by an indirect immunofluorescent method in both the cytoplasm and nucleus of large mononuclear cells that had no granules in bone marrow. On admission, the hemoglobin was 3.1 g/dl and no reticulocytes were detected in the peripheral blood smear. Bone marrow examination revealed a normocellular marrow with erythroid hypoplasia and M/E ratio of 7.38. Large basophilic erythroblasts containing vacuoles were also noticed. Elevation of indirect bilirubin and hemoglobinuria suggested intravascular hemolysis. Transient mild thrombocytopenia associated with increased PAIgG was observed. It is likely that B19 virus infection caused hemolysis which contributed to severe anemia.     

Epstein-Barr virus-related post-transplant lymphoproliferative disorder occurring after bone marrow transplantation for aplastic anemia in Down’s syndrome

It is well established that Down’s syndrome exhibits a predisposition to development of leukemia, however, association between aplastic anemia and Down’s syndrome is exceptional. Herein, we describe a case of aplastic anemia occurring in Down’s syndrome following post-transplant lymphoproliferative disorder (PTLD) after bone marrow transplantation (BMT). A 27-year-old Japanese male with Down’s syndrome presented with a headache. Laboratory tests revealed severe pancytopenia, and bone marrow biopsy demonstrated hypocellular bone marrow with decrease of trilineage cells, which led to a diagnosis of aplastic anemia. One year after diagnosis, he was incidentally found to have an anterior mediastinal tumor, which was histopathologically diagnosed as seminoma. Subsequently, he received BMT from a female donor, and engraftment was observed. Three months after transplantation, he experienced cough and high fever. Biopsy specimen from the lung revealed diffuse proliferation of large-sized lymphoid cells expressing CD20 and EBER. These lymphoid cells had XY chromosomes. Thus, a diagnosis of EBV-associated PTLD was made. This is the seventh documented case of aplastic anemia occurring in Down’s syndrome. Association between aplastic anemia and Down’s syndrome has not been established, therefore, additional clinicopathological studies are needed. Moreover, this is the first case to undergo BMT for aplastic anemia in Down’s syndrome. Although engraftment was observed, he developed EBV-positive PTLD. The neoplastic cells of the present case were considered to be of recipient origin, although the majority of PTLD cases with BMT are of donor origin.     

Bone marrow examination in Egyptian patients with bicytopenia/pancytopenia

The incidences of diseases that cause peripheral blood (PB) cytopenias differ between countries according to the prevalent health problems. This study was carried out in order to identify bone marrow findings and underlying disorders in adult Egyptian patients with PB cytopenias (bicytopenia and pancytopenia). The study involved patients newly diagnosed as having PB cytopenias over a period of 1 year. Clinical and hematological parameters of patients were recorded. Bone marrow specimens were examined. Sixty-two pancytopenia and 50 bicytopenia patients were included in the study. The most common cause of pancytopenia was clonal hematopoietic disorders (34 %), hypersplenism (27 %), and aplastic anemia (21 %). The most common cause of bicytopenia was clonal hematopoietic disorders (34 %), ITP (24 %), and hypersplenism (18 %). Lymphoid neoplasms were the most common and account for 57 % of clonal pancytopenia patients and 65 % of clonal bicytopenia patients. Most hypersplenism patients (86 %) had history of hepatitis C viral infection. Our results show that, in Egypt, clonal hematopoietic disorders, hypersplenism due to chronic liver disease, ITP, and aplastic anemia are the common causes of PB cytopenias. In our setting, causes underlying bicytopenia are as important as those of pancytopenia.     

Initial bone marrow findings in multiple myeloma. Significance of plasma cell nodules

A retrospective review of bone marrow specimens from 235 patients with multiple myeloma and 148 patients with reactive plasmacytosis was performed in an attempt to evaluate the usefulness of bone marrow sections in distinguishing between these conditions. Although the presence of large homogeneous nodules and/or infiltrates of plasma cells in bone marrow sections remains the best criterion for the diagnosis of myeloma, a few specimens (2%) from patients with reactive plasmacytosis also showed this feature. In addition, 26% of the patients with myeloma had bone marrow sections that were considered nondiagnostic in that they lacked recognizable homogeneous nodules and/or infiltrates of plasma cells. Finally, distinguishing multiple myeloma from bone marrow involvement by lymphoplasmacytic lymphomas can be very difficult, if not impossible, based on findings in the sections alone.     

氯甲基苯甲酰氨标记骨髓间充质干细胞在免疫介导骨髓衰竭小鼠模型体内的归巢

背景：再生障碍性贫血是T淋巴细胞免疫亢进破坏造血干祖细胞的一种异常免疫反应性疾病。骨髓间充质干细胞具有支持造血功能同时具有免疫调控作用。 目的：观察骨髓间充质干细胞移植骨髓衰竭模型小鼠体内的归巢情况。 方法：将BALB/c小鼠随机分成正常对照组、骨髓衰竭模型组和骨髓间充质干细胞移植组,于第6天将已标记氯甲基苯甲酰氨的BALB/c小鼠骨髓间充质干细胞经尾静脉注射途径移植给骨髓衰竭模型小鼠,采用流式细胞术和组织学荧光显微镜观察标记细胞在不同组织的动态分布。造模第14 天,观察各组小鼠的平均生存时间、外周血血象和骨髓形态学特征。 结果与结论：骨髓间充质干细胞经尾静脉输注后24 h在受体小鼠骨髓中可发现氯甲基苯甲酰氨阳性标记细胞,72 h时阳性标记细胞数量增多(P < 0.05)。骨髓间充质干细胞移植组小鼠濒死或处死前的白细胞、血红蛋白、血小板、骨髓单个核细胞数与模型组小鼠濒死时相比显著升高(P < 0.01)。骨髓衰竭模型组比骨髓间充质干细胞移植组平均生存时间短(P < 0.05)。结果证实,骨髓间充质干细胞输入骨髓衰竭模型体内能归巢至骨髓,促进造血恢复,减轻骨髓衰竭程度,显著延长生存时间。       

Trisomy 1q in a patient with severe aplastic anemia

Aplastic anemia is a rare, serious disease characterized by hypocellular bone marrow and pancytopenia in the peripheral blood. Most cases are acquired, idiopathic, and without gross cytogenetic abnormalities. A few chromosome abnormalities have recurred among a small subset of patients, most commonly trisomy 8 and monosomy 7. Some of these chromosome abnormalities have prognostic and therapeutic significance, although for most the clinical relevance is not known. We present the case of a 40-year-old man with idiopathic severe aplastic anemia in bone marrow cells with trisomy of the whole long arm of chromosome 1 due to an unbalanced translocation between chromosomes 1 and 15 at breakpoints of q10 and 15q10. This clonal abnormality (which, to our knowledge, has not been previously reported in a patient with aplastic anemia) suggests that genes on 1q may be involved in marrow aplasia.