同种异基因骨髓移植5例报告

我们近年用同种异基因骨髓移植（ａｌｌｏ－ＢＭＴ）治疗急性放射病和白血病５例。其中２例为事故性急性放射病，由ＨＬＡ半相合的供体供髓，１例骨髓移植成功后存活９０天，后因两肺弥漫性纤维化而死于呼吸衰竭。３例白血病患者移植后白血病缓解，均持续无病生存。采用小剂量环胞霉素Ａ（ＣＳＡ）＋氨甲喋呤（ＭＴＸ）预防急性移植物抗宿主病（ａＧＶＨＤ），结果４例骨髓移植成功者其ａＧＶＨＤ均控制在Ⅱ°以下，并经用甲基强的松龙治疗后症状控制。     

用BUCY2方案预处理的异基因骨髓移植治疗急性白血病

利用ＢＵＣＹ２方案作预处理对２例急性因病患者实施同种异基因骨髓移植，输入的供体骨髓分别于术后第１８天和１７天植活；ＢＵＣＹ２预处理的毒性较小，化疗反应较易耐受；２例患者均于术后第１８天出现急性移植物抗宿主病（ＧＶＨＤ，Ⅱ级），现已持久植活达２年和１年半，术后５个月复查时，患者的造血系统仍为供体来源。     

非血缘关系异基因骨髓移植19例临床分析

目的 探讨非血缘关系异基因骨髓移植（URD－BMT）的疗效和相关合并症。方法 我所1998年8月－2001年2月行19例URD－BMT。预处理方案：2例以全身照射（TBI）为主的方案,其余均用化疗方案。移植物抗宿主症（GVHD）的预防：所有患者均接受环孢素A和短程甲氨蝶呤方案。其中7例用霉酚酸酯（MMF）,1例用CD3＋CD25,9例用抗胸腺细胞球蛋白（ATG）,其中1例骨髓经免疫毒素体外去除T淋巴细胞。骨髓回输：18例经股动脉插管输入。结果 19例中2例因观察期尚短不能评价,其余17例均植活。超急性GVHD发生7例;急性GVHDⅡ-Ⅳ度为9／17例,累积发生率为53.0%。采用单因素分析表明,HLA配型不合、未用ATG、MMF、输入细胞数枵植活时间,对Ⅱ-Ⅳ度急性GVHD的发生率均无显著影响。感染情况：移植后5周内发热的患者为11／17例。在随访期内,10例发生巨细胞病毒感染。存活情况：19例中死亡6例。18个月无病存活58.3%。结论 URD－BMT作为治疗恶性血液病的方法,因移植相关病死率较高,尚不能大规模开展。当高危急性白血病、慢性髓细胞白血病的患者没有合适的亲缘供者时,URD－BMT不失为治疗的措施之一。     

异基因骨髓移植新策略:骨髓腔内骨髓移植

骨髓移植逐渐成为治疗造血障碍疾病、先天性免疫缺陷疾病、自身免疫性疾病的重要治疗方法。异基因骨髓细胞的植入可以诱导抗原匹配器官的免疫耐受。临床上广泛地把骨髓移植作为一种诱导免疫耐受的方法,但由于预处理的毒性、移植物抗宿主病(GVHD)、植入失败带来的高发病率和死亡     

异基因骨髓移植后并发肺部感染的临床研究

肺部感染是骨髓移植 (BMT)后最常见的并发症之一 ,也是BMT受者的主要死因。我院 1998年 11月至 2 0 0 2年 11月收治并发肺部感染的异基因骨髓移植 (Allo BMT)患者 2 9例 ,17例 (5 9% )治疗有效 ,死亡 8例 ,自动出院 4例。对象与方法　 2 9例Allo BMT患者 ,男 2 1例 ,女 8例 ,年龄 16～ 5 2岁 (中位年龄 32岁 ) ,2 4例行非血缘Allo BMT ,5例行血缘Allo BMT ,基础疾病为慢性粒细胞性白血病 16例 ,急性白血病 10例 ,骨髓增生异常综合征 2例 ,多发性骨髓瘤 1例。同期行Allo BMT患者共 94例。临床表现 :发热、咳嗽 2 9例 ,咳痰 2 5例 …     

Graves病合并自身免疫性肝病1例并文献复习

<正>甲状腺功能亢进症导致肝损伤的原因有甲状腺激素增多引起的损伤、抗甲状腺药物治疗引起的药物性肝损伤(DILI)及可能合并的其他肝脏疾病等^[1,2]。Graves病(Graves’ disease, GD)是一种全身性自身免疫性疾病,也是甲状腺功能亢进症最常见的表现形式。2010年一项研究报道,另一种自身免疫性疾病,如类风湿关节炎、恶性贫血、系统性红斑狼疮等在GD患者的发生率为9.7%,在桥本甲状腺炎的发病率为14.3%^[3]。     

异基因造血干细胞移植后闭塞性毛细支气管炎综合征-2例报告并文献复习

目的:探讨异基因造血干细胞移植(allo-HSCT)后闭塞性毛细支气管炎综合征(BOS)的诊断和治疗。方法:对2例恶性血液病患者allo-HSCT后发生BOS的临床特点和治疗进行分析并结合文献复习。结果:2例患者移植后造血均顺利重建,未发生急性移植物抗宿主病(aGVHD),分别于移植后5月和6月发生广泛型慢性移植物抗宿主病(cGVHD),经治疗后病情仍有反复,分别于移植后9月和11月发生BOS,给予免疫抑制剂、静脉免疫球蛋白、阿奇霉素及局部使用β2受体激动剂及布地奈德吸入治疗。1例在治疗4周后病情有改善,另1例病情无改善。结论:cGVHD是allo-HSCT后发生BOS的重要危险因素,对BOS的早期诊断和干预是改善其预后的关键。     

异／同基因骨髓移植后存活20—30年的患者的免疫状况

作者通过问卷调查的方式追踪了解骨髓移植(BMT)后存活20～30年的患者的感染发生率以及抗体水平,并综合评估其免疫状况。 方法 72例BMT后存活20～30年的患者,其中的33例其供髓者中的16例通过抽血测定淋巴细胞分类计数和抗体水平。除1例接受肺移植外,所有患者在BMT15年后没有接受免疫抑制药物、预防性使用抗生素以及静脉注射免疫球蛋白。用流式细胞仪测定单个核细胞分类计数(包括B细胞及其亚型,CD4T细胞及其亚型,NK细胞,单核细胞),通过实时定量PCR法测定T细胞更新标志即T细胞受体清除周期(T cell receptor excision circle,TREC)水平,ELISA法测定血清总IgC_2水平和特异性IgG含     

异基因骨髓移植逆转慢性粒细胞性白血病之骨髓纤维化(附1例报告)

目的：探讨异基因骨髓移植（ａｌｌｏ－ＢＭＴ）治疗慢性粒细胞性白血病（ＣＭＬ）骨髓纤维化的效果。方法：以ａｌｌｏ－ＢＭＴ治疗１例ＣＭＬ合并骨髓纤维化患者,并进行临床观察。结果：骨髓纤维化程度明显改善,骨髓有核细胞增生活跃;但白细胞升至正常约需９０ｄ。结论：ａｌｌｏ－ＢＭＴ治疗ＣＭＬ骨髓纤维化有肯定疗效。     

Severe autoimmune thrombocytopenia after allogeneic bone marrow transplantation for aplastic anemia

Autoimmune thrombocytopenia (AITP) after bone marrow transplantation (BMT) was suggested to occur by immune dysregulation mainly in association with graft-versus-host disease (GVHD). Here we present a patient who developed severe AITP after BMT. A 40-year-old woman with severe aplastic anemia received a BMT from a partially HLA-matched brother. Despite myeloid and erythroid engraftments, platelet recovery was delayed. All bone marrow cells were 46,XY and were derived from the donor. Grade I acute GVHD involving skin developed from day 34 posttransplantation, but promptly responded to prednisolone in addition to a prophylactic dose of tacrolimus. With the tapering of prednisolone, thrombocytopenia progressed without substantial changes in the white blood cell count, hemoglobin concentration, or reticulocyte count. On day 188, the patient developed chronic GVHD involving skin and liver, which promptly responded to the readministration of prednisolone and increased tacrolimus. However, the patient's platelet count decreased to 9 x 10(9) cells/L on day 222. The platelet-associated immunoglobulin G (PAIgG) values were elevated. Bone marrow examination showed hypercellularity with plentiful megakaryocytes. The number of colony-forming units-megakaryocyte was within the normal range. The elevated PAIgG values and a correlation between thrombocytopenia and the intensity of the immunosuppressive agents strongly suggested a causative role of the autoimmune mechanisms for thrombocytopenia in this patient.     

Allogeneic bone marrow transplantation as primary therapy for chronic myelomonocytic leukemia

Summary This is the first report of a successful bone marrow transplantation for chronic myelomonocytic leukemia. A 41-year-old woman with chronic myelomonocytic leukemia received, as primary treatment, a novel preparatory regimen consisting of high dose fractionated total body irradiation and high dose VP-16 chemotherapy followed by allogeneic marrow transplantation from her histocompatible brother. The patient is now more than two years after marrow transplantation with normal blood counts and a normal bone marrow which is of donor type. For younger patients with this disease who have a histocompatible sibling donor, bone marrow transplantation may represent a valid therapeutic option with curative potential.This investigation was supported by PHS Grants CA 30206 and CA 33572 awarded by the National Cancer Institute, DHHS     

Allogeneic bone marrow transplantation for high risk non-hodgkin's lymphoma during first complete remission

Summary Allogeneic bone marrow transplantation from histocompatible sibling donors was performed in six patients with extranodal involvement of high grade lymphoma during first complete remission. Five patients had lymphoblastic lymphoma and one had diffuse undifferentiated lymphoma. The cytoreductive/immunosuppressive regimen consisted of total body irradiation and high dose cyclophosphamide. Four patients are alive in complete remission at 8 months, 14 months, 21 months and 47 months post transplantation. One patient who relapsed 7 months after his initial transplantation underwent a second transplantation but another relapse 17 months later led to his death. One patient died of chronic graft-versus-host disease and at autopsy there was no evidence of lymphoma. These data demonstrate that allogeneic bone marrow transplantation can produce durable remissions in patients with high grade lymphoma who present with bone marrow, central nervous system and/or skin involvement.     

Allogeneic marrow transplantation for chronic granulocytic leukemia

Summary Six patients with Philadelphia-chromosome (Ph' +)-positive chronic granulocytic leukemia were transplanted from their HLA-identical siblings after conditioning with cyclophosphamide and 1'000 rad total body irradiation. All received cyclosporin-A for prophylaxis of Graft-versus-Host disease. All patients showed prompt engraftment and all are cytogenetically and clinically in complete remission. Two patients had transient mild signs of Graft-versus-Host-disease and one patient had unilateral facial nerve paresis of unknown origin. All are ambulatory and well 6–18 months (median 10 months) after transplantation.Supported by Grants of the Swiss Science Foundation 3.846.0.79, the Swiss Cancer League FOR.141.LR.79 (3) and the Swiss Public Health Service     

Amiodarone-associated bone marrow granulomas: a report of 2 cases and review of the literature

Amiodarone therapy is associated with several adverse effects, including hematologic ones such as pancytopenia, hemolytic anemia, and aplastic anemia. Very few cases of amiodarone-associated bone marrow granulomas have been reported. We report 2 cases of amiodarone-associated bone marrow granulomas. Patient 1 was an 81-year-old man who presented with leukopenia, thrombocytopenia, and hepatosplenomegaly after 2 years of amiodarone therapy. Patient 2 was an 80-year-old man who presented with pancytopenia 2 1/2 years after starting amiodarone treatment. Both patients had normal blood counts before amiodarone therapy. Bone marrow biopsies showed noncaseating granulomas in both patients. We reviewed the literature available on Medline for amiodarone-associated bone marrow granulomas and found 8 reported cases of amiodarone-associated bone marrow granulomas. One case also featured amiodarone-associated hepatic granulomas. Amiodarone therapy was stopped in 5 cases, with improvement of the granulomas occurring in 3 cases. We conclude that bone marrow granulomas, although rare, should be considered as a differential diagnosis for patients undergoing amiodarone therapy and presenting with cytopenias.     

Treatment of autoimmune diseases in mice by a new method for allogeneic bone marrow transplantation

Remarkable advances have been made in bone marrow transplantation (BMT), which has become a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency, and also autoimmune disease. Using various animal models, allogeneic (allo) BMT has been found to be useful in the treatment of various autoimmune diseases. In MRL/lpr mice, which are radiosensitive (<8.5 Gy) and are an animal model for autoimmune diseases, conventional BMT resulted in only transient effects; the manifestations of the autoimmune diseases recurred 3 months after BMT. Using MRL/lpr mice, we have very recently established a new strategy for allo BMT. We injected bone marrow cells (BMC) directly into the bone marrow cavity (intrabone marrow [IBM] injection) of recipients that had received fractionated irradiation. This 'IBM-BMT' was found to be effective in treating autoimmune diseases in radiation-sensitive and chimeric-resistant MRL/lpr mice. In addition, this strategy was found to be applicable for the transplantation of organs. We believe that these strategies for BMT and organ transplantation herald a new era in transplantation.     

Allogeneic bone marrow transplantation for systemic AL amyloidosis

Low-intensity chemotherapy is ineffective in most patients with AL amyloidosis, probably because clinical benefit requires regression of the amyloid deposits, and this occurs only very gradually after the underlying plasma cell dyscrasia has been suppressed. We report the first successful allogeneic bone marrow transplant (allo-BMT) for AL amyloidosis, which after 3 years was associated with complete clinical recovery. This supports the idea that there may be a brief window of opportunity in patients with AL amyloidosis during which dose-intensive chemotherapy is feasible and most likely to produce clinical benefit.     

Autologous bone marrow transplantation in decompensated liver: Systematic review and meta-analysis

AIM: To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease.METHODS: Medline, EMBASE, PubMed, Science Direct, and the Cochrane Library were searched for relevant studies. Retrospective case-control studies were included along with randomized clinical trials. Meta-analysis was performed in line with recommendations from the Cochrane Collaboration software review manager. Heterogeneity was assessed using a random-effects model.RESULTS: Four randomized controlled trials and four retrospective studies were included. Cell transplantation increased serum albumin level by 1.96 g/L (95%CI: 0.74-3.17; P = 0.002], 2.55 g/L (95%CI: 0.32-4.79; P = 0.03), and 3.65 g/L (95%CI: 0.76-6.54; P = 0.01) after 1, 3, and 6 mo, respectively. Patients who had undergone cell transplantation also had a lower level of total bilirubin [mean difference (MD): -1.37 mg/dL; 95%CI: -2.68-(-0.06); P = 0.04] after 6 mo. This decreased after 1 year when compared to standard treatment (MD: -1.26; 95%CI: -2.48-(-0.03); P = 0.04]. A temporary decrease in alanine transaminase and aspartate transaminase were significant in the cell transplantation group. However, after 6 mo treatment, patients who had undergone cell transplantation had a slightly longer prothrombin time (MD: 5.66 s, 95%CI: 0.04-11.28; P = 0.05). Changes in the model for end-stage liver disease score and Child-Pugh score were not statistically significant.CONCLUSION: Autologous bone marrow transplantation showed some benefits in patients with decompensated liver disease. However, further studies are still needed to verify its role in clinical treatment for end-stage liver disease.     

HLA半相合血缘性骨髓移植治疗慢性粒细胞白血病4例

目的:探索半相合未去除T细胞骨髓移植治疗慢性粒细胞白血病的可行性。方法:4例慢性粒细胞白血病患者接受HLA1或2个位点不相合亲缘骨髓移植。用阿糖胞苷、环磷酰胺和全身照射进行预处理,供者应用GCSF250μg/d,连用7d后采髓。移植物抗宿主病(GVHD)预防除用环孢菌素A(CsA)和甲氨蝶呤(MTX)外,在移植前第4天～第1天用抗胸腺细胞球蛋白ATG(兔抗)2.5mg/(kg·d),移植后第7天开始加用霉酚酸酯1.0g/d。结果:患者移植后均获得造血重建,中性粒细胞>0.5×109/L和血小板>20×109/L的中位时间分别是12.5(10～14d)和22d(18～25d)。4例患者发生急性Ⅰ度GVHD,其中1例2个位点不相合者进展为急性肠道和肝脏Ⅳ度GVHD,于+81d合并感染死亡。1例发生迟发性出血性膀胱炎。中位随访时间20个月(5～25个月)。无病存活3例,其中2例存活在1年以上。结论:供者应用GCSF后采髓,多种免疫抑制剂联合应用的HLA不全相合未去除T细胞骨髓移植,在治疗慢性粒细胞白血病过程中,有效地降低了急性重症GVHD发生,提高了无病生存。     

No narcosis for bone marrow harvest in autologous bone marrow transplantation

Summary A prospective study with mild general analgesia and sedation together with local anesthesia during bone marrow harvest was performed. Thirty-one patients underwent 33 bone marrow collections. Pretreatment consisted of 100 mg meperidine i.m. and 20 mg diazepam i.m. 1 h before start of procedure. Eight patients got additional meperidine and diazepam during the procedure, all patients got lidocaine 1% locally. A mean volume of 1.321 was obtained with 42.5 punctures. Twenty-two patients had no complications, 4 vomited, 4 had easily correctable hypotension of short duration, one got oxygen for cyanosis of short duration. Acceptance was good in 23 patients, in 6 reasonably well, in two bad. Only one patient experienced pain problems, due to suction. Anxiety was no major problem due to good information before the procedure and mild sedation.This form of anesthesia for bone marrow collection is a safe procedure, it is generally well accepted by the patient and it can be performed on an out-patient basis.