再生障碍性贫血患者的染色体研究

很多化学和物理因素可以损伤人体细胞中的染色体,使其产生断裂、粘连、内复制增多等。我们对再生障碍性贫血患者作细胞遗传学研究的目的在于了解本病的发病原理,确定某些药物或化学、物理因素引起再生障碍性贫血的性质,从而可以更有效地预防和治疗本病。此外,对继发性再生障碍性贫血可能提供一种客观的检查指标。现将我们一年多来的初步研究结果报道如下。     

再生障碍性贫血中医药防治研究进展

再生障碍性贫血是由多种原因引起的骨髓造血功能衰竭,以全血细胞减少为特征的一种综合病症。目前普遍认为其发病机理与免疫因素介导的造血干细胞受损导致造血微环境异常相关。近年来,中医药以其独特的理论体系和治疗方法,在再生障碍性贫血的病因病机及防治防等研究方面取得了较大进展。中医药防治再生障碍性贫血一般从肾精亏虚、毒损髓络、生血乏源入手,以补肾填精、生血解毒为治疗法则,采用中药方剂或/和联合西药,可提高治疗有效率,降低西药的毒副作用,并可以调控T淋巴细胞的分化及相关细胞因子的表达。中药治疗可以改善骨髓造血微环境、不同程度的恢复骨髓的造血功能,提高患者的生存质量。现就中医药对此病的相关研究作一综述。     

环孢霉素A治疗再生障碍性贫血临床观察

单用雄激素治疗再生障碍性贫血 ,完全缓解率3 5 %～ 5 3 %。我们于 1 995年 1月～ 1 999年 4月应用环孢霉素 A、雄激素治疗再生障碍性贫血 2 0例 ,取得较好效果 ,现报告如下。1　临床资料1 .1　一般资料　 2 0例中 ,男 1 2例 ,女 8例 ,年龄1 1～ 46岁 ,平均 3 3岁。治疗前病程 1～ 48个月。诊断标准参照 1 987年第四届再障学术会议修订的标准 ,其中慢性再障 1 3例 ,重型再障 I型 5例 ,重型再障 型 2例 ;慢性再生障碍性贫血患者在应用环孢霉素 A治疗前均使用过康力龙、丙酸宰丸酮、左旋咪唑、一叶秋碱、再障生血片、泼尼松、输注脐血或胎…     

49例全血细胞减少的鉴别诊断

全血细胞减少是指周围血液中红细胞、白细胞、血小板计数均低于正常范围 ,它不是疾病的诊断 ,而是引起血液有形成分减少的某些疾病的共同临床现象。因此了解全血细胞减少的原因、诊断 ,对治疗措施的实施及预后评价十分重要。我院自1 989年 1月至 1 998年 8月共收治全血细胞减少病人 49例 ,现结合这组病人就其病因分类、诊断步骤及鉴别要点分析报告如下。1　临床资料1 .1　一般资料　 49例患者中 ,男 2 3例 ,女 2 6例 ,年龄 1 3～ 69岁 ,平均年龄 3 8岁。再生障碍性贫血2 5例 ,急性再生障碍性贫血 2例 ,慢性再生障碍性贫血 2 3例 ;急性白血病…     

抗人淋巴细胞免疫球蛋白的临床应用进展

抗人淋巴细胞免疫球蛋白制品已经临床研究,证实有效,其中包括在肾、心脏、肝等器官移植的免疫排斥预防和治疗,骨髓移植的移植物抗宿主反应的预防,以及再生障碍性贫血的治疗等.     

本期导读

儿童血液病的救治一直是我们国家及全体民众关心、关注的焦点,尤其对于危害性、致贫致困率较高的良性疾病,如再生障碍性贫血及少见遗传性疾病。临床研究安全高效、适合中国国情的救治方案尤为重要,常见治疗相关并发症的优化处理也同样需要引起重视。针对儿童重型再生障碍性贫血(severe aplastic anemia,SAA)的一线治疗方案,国内外指南共识一致推荐首选同胞全相合造血干细胞移植,长期治愈率可达80﹪以上,但我国的实际情况不容乐观。据中华医学会血液学分会造血干细胞移植应用学组2019年最新统计显示,全年完成全年龄段再生障碍性贫血患者移植共1260例,同胞相合及非血缘相合移植仅占38﹪(22﹪及16﹪),单倍体移植已超半数。供体来源较为容易的单倍体移植,是否成为儿童重型再生障碍性贫血安全有效的替代性选择治疗方案,前期已有的多项研究表明,3年及5年OS率、FFS率均与同胞相合移植接近,但急性移植物抗宿主病、慢性移植物抗宿主病、围植入综合征、骨髓增殖不良以及病毒感染等并发症仍需足够关注。     

抗人淋巴细胞免疫球蛋的临床应用进展

抗人淋巴细胞免疫球蛋白制品已经临床研究,证实有效,其中包括在肾,心脏,肝等器官移植的免疫排斥预防和治疗,骨髓移植的移植物抗宿主反应的预防,以及再生障碍性贫血的治疗等。     

再生障碍性贫血和急性白血病血清氨基酸变化的观察

<正> 再生障碍性贫血和急性白血病是严重的血液病。当今世界科技工作者正在为攻克这些顽症探讨其发病原因,机理及新的有效治疗方法。随着分子生物学的发展,氨基酸分析作为洞察人体奥秘的一个窗口越来越受到重视。Cooney(1970年)曾观察到一例白血病患者有天冬氨酸↓,迄今国内尚未见到急性白血病氨基酸变化的报导,有关再生障碍性贫血血清氨基酸的变化国内外尚未见到报导。     

再生障碍性贫血中残存造血细胞的生物学特征

再生障碍性贫血是T细胞免疫介导的骨髓衰竭,造血前体细胞在淋巴细胞及细胞因子作用下凋亡增加.再生障碍性贫血不仅造血干/祖细胞池萎缩,其残存造血细胞还存在功能缺陷,与老化造血干细胞特征相似.在免疫攻击和造血压力作用下,残存造血细胞增殖能力减退、对细胞因子反应不良,端粒缩短、遗传不稳定,或虽逃逸免疫攻击,发生克隆性造血和向M...     

细胞凋谢与鸡传染性贫血

细胞凋谢与鸡传染性贫血曹永长,毕英佐（华南农业大学动物科学系,广州５１０６４２）关键词鸡传染性贫血,细胞凋谢鸡传染性贫血（ＣｈｉｃｋｅｎＩｎｆｅｃｔｉｏｕｓＡｎｅｍｉａ）是由鸡贫血病毒（ＣＡＶ）引起的,以再生障碍性贫血和全身淋巴组织萎缩造成免疫抑制为...     

四物汤对再生障碍性贫血小鼠骨髓细胞增殖的影响研究

目的研究四物汤对再生障碍性贫血（AA）小鼠骨髓细胞体外增殖的影响,探讨其治疗AA的机制。方法采用流式细胞仪、骨髓造血祖细胞培养等技术,检测四物汤对AA小鼠骨髓细胞的增殖变化。结果 四物汤能促进骨髓有核细胞进入G2／S期、增加CFU—GM、CFU-E、BFU-E集落数,且与自然恢复组有明显增强的差异。结论 四物汤在体内有促进AA小鼠骨髓细胞增殖的作用,为补血药治疗AA提供了实验与理论依据。     

Marrow transplantation for severe aplastic anemia associated with exposure to quinacrine

Severe aplastic anemia developed in a patient after administration of quinacrine for treatment of discoid lupus erythematosus. Marrow transplantation was performed from an HLA genotypically identical sister after conditioning with cyclophosphamide. Quinacrine which was accumulated in the patient tissues did not interfere with engraftment, suggesting that the drug has no direct cytotoxic effect on hematopoietic stem cells. This study extends our previous observation that severe aplastic anemia acquired after exposure to drugs or toxins can be cured by marrow transplantation.     

Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility.

Between February 1971 and October 1980, 34 patients with leukemia or aplastic anemia received bone marrow transplants from HLA-identical siblings whose lymphocytes did not react in a mixed leukocyte culture. The donors of 10 patients were ABO-incompatible, and for five pairs the ABO incompatibility was major. Plasma exchanges followed by a red blood cell exchange transfusion reduced the anti-A titres to 1:4 or less in these patients. The ABO incompatibility had no adverse effect on the results of marrow transplantation. Twenty-two patients, including 16 of the 20 who received their transplant after Jan. 1, 1980, are still living. Seven of the 15 patients with acute leukemia have survived 89 to 466 days, and 4 of the 6 with chronic myelogenous leukemia (CML) have survived 117 to 545 days. Of the 13 patients with aplastic anemia, 11 are alive up to 8 years after transplantation. Marrow transplantation, when possible, is the treatment of choice for young patients with acute leukemia in remission and for patients with aplastic anemia. Marrow transplantation may also prove to be effective in patients with CML.     

集落刺激因子治疗重型再生障碍性贫血疗效和安全性的Meta 分析

目的:通过Meta分析评价粒系或粒单系集落刺激因子(G-CSF或GM-CSF)对接受免疫抑制治疗(IST)的重型再生障碍性贫血(SAA)患者的疗效和安全性。方法:使用相关检索词检索MEDLINE、Cochrane Library、EMBASE、CNKI及CBM数据库,检索时间1990年1月～2011年12月。纳入G-CSF或GM-CSF治疗SAA的随机对照研究。用Review Manager4.2统计软件对数据进行Meta分析。结果:共纳入4篇文献,共466例SAA患者。Meta分析结果显示:①IST疗效:G-CSF/GM-CSF组与对照组的SAA患者对比,近远期疗效与生存率均无显著差异:总体生存率[OR=1.15,95%C(I0.73,1.82),P=0.54]、完全缓解率[OR=1.20,95%CI(0.71,2.02),P=0.50]、早期总体有效率[OR=1.61,95%CI(0.85,3.03),P=0.14]、远期总体有效率[OR=1.17,95%CI(0.78,1.74),P=0.45];②IST相关感染:IST治疗早期感染发生率、严重感染发生率、感染相关死亡率方面均未优于对照组;③G-CSF/GM-CSF组的复发率低于对照组,差异显著[OR=0.57,95%C(I0.35,0.93),P=0.02];④G-CSF/GM-CSF组远期随访发生克隆性病变的发生率与对照组无统计学差异,恶性肿瘤(MDS/AML)发生率[OR=0.90,95%CI(0.41,1.99),P=0.79]、PNH发生率[OR=1.48,95%CI(0.65,3.33),P=0.35]。结论:G-CSF/GM-CSF应用于接受IST治疗的SAA患者,尚不能证明具有提高总体生存率、完全缓解率、总体有效率、减少感染和感染相关死亡率等优势。虽然有可能降低复发率,也不增加远期克隆性病变发生率,但还需要更严格设计的大样本双盲随机对照试验,并进行更为长期的随访研究。     

The release of interleukin-2 (IL-2) and colony stimulating activity (CSA) in aplastic anemia patients: opposite behaviour with improvement of bone marrow function

Peripheral blood cells from patients with aplastic anemia were tested for their ability to release interleukin-2 (IL-2) and colony stimulating activity (CSA) before treatment. IL-2 release--as measured in the mouse thymocyte assay--was abnormally high in 18/34, and abnormally low in 10/34 patients. "Low" release was due to simultaneous release of thymocyte inhibitors. In 18 patients who achieved self-sustaining hemopoiesis after high dose immunosuppressive therapy, excess IL-2 release decreased to low levels (p less than 0.001), and the release of inhibitors disappeared. In contrast, the release of CSA by patient cells--which did not correlate with peripheral blood monocyte counts--either remained high or increased to excessively high values in 24/24 patients tested before and after successful immunosuppressive treatment. Patients with stable hemopoietic grafts after bone marrow transplantation for aplastic anemia, did not release excess CSA. It is concluded that IL-2 and CSA play opposite roles in aplastic anemia. High IL-2 release seems associated with disease activity, whereas high CSA-release appears to reflect a repair mechanism.     

Cutting edge: activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia

Myelosuppressive cytokines, in particular IFN-gamma and TNF-alpha, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-gamma and TNF-alpha in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-gamma and TNF-alpha on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.     

Hematological Complications of Phenylbutazone Therapy: Review of the Literature and Report of Two Cases

Two examples of hematological toxicity following phenylbutazone therapy are described, one of agranulocytosis and one of aplastic anemia. In the first case, prednisolone in a dosage of 20 mg. daily restored neutrophil percentage and the total leukocyte count to normal, but the patient with aplastic anemia, having shown no response to corticosteroid therapy, became dependent on repeated blood transfusion.The English literature on the hematological toxicity of phenylbutazone is reviewed. Ten fatal cases of agranulocytosis have been recorded, as have eight cases of aplastic anemia, of which five proved fatal. Other toxic effects noted have included leukopenia, depression of erythropoiesis, megaloblastic anemia, thrombocytopenia and leukemia.     

NK and K cell activity in children with leukemias and aplastic anemias before and after allogeneic bone marrow transplantation

Mononuclear leukocytes from the peripheral blood and bone-marrow of children affected with aplastic anemia and leukemia were investigated for K-cell activity (antibody-dependent cellular cytotoxicity) and NK-cell activity before and after allogenous bone-marrow transplantation. 51Cr liberation test against murine Graffi erythroblast leukemic cells covered with xenoantibodies and K-562 cells were used for identification. Strongly lowered NK- and K-cell activities could be found in aplastic anemia prior to bone-marrow transplantation. However, NK-cell activity was only lowered significantly in leukemic patients with indication of bone-marrow transplantation. K-cell and NK-cell activities normalised after bone-marrow transplantation. K-cell and NK-cell activities could be observed to be reconstituted very early after bone-marrow transplantation.     

Complement-dependent hematopoietic inhibitors in the sera of patients with aplastic anemia and paroxysmal nocturnal hemoglobinuria

The sera of 14 out of 48 patients with aplastic anemia and four out of nine patients with paroxysmal nocturnal hemoglobinuria (PNH) contained complement-dependent hematopoietic inhibitory activity against allogeneic marrow progenitor cells. Some sera with hematopoietic inhibitory activity, however, demonstrated no effect on autologous marrow progenitor cells. Hematopoietic inhibitory activity was absorbed by pooled, packed platelets. Serum hematopoietic inhibitory activity was present in both IgM and IgG fractions. These data suggested that serum hematopoietic inhibitors are alloantibodies and might be associated with graft rejection in the transplanted marrow of patients with aplastic anemia and PNH.     

Anti-thoracic duct lymphocyte globulin stimulates human megakaryocytopoiesis in vitro

Anti-thoracic duct lymphocyte globulin (ALG) therapy is effective in patients with aplastic anemia. We examined the effect of ALG on human megakaryocyte progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) in vitro. Normal human bone marrow mononuclear cells (MNC) were cultured in plasma clots with varying concentrations of ALG or non-immunized horse IgG. After 12 days of culture, significant megakaryocyte colony formation was observed in cultures containing ALG but not in cultures containing non-immunized horse IgG. The peak stimulatory effect seemed to occur with 10-25 micrograms/ml of ALG. When marrow MNC, depleted of adherent and T cells, were cultured in plasma clots with ALG, its stimulatory effect on megakaryocytopoiesis decreased markedly. Finally, it was demonstrated that ALG stimulated marrow MNC to produce a factor stimulatory for CFU-Meg. The in vitro megakaryocytopoietic stimulatory effect of ALG may be related to its clinical efficacy in some patients with aplastic anemia.