骨髓联合外周血造血干细胞移植治疗重型再生障碍性贫血

目的　探讨非清髓性、骨髓和外周血造血干细胞移植治疗高风险重型再生障碍性贫血 (SAA)及移植后供者干细胞输注 (DSI)的疗效和并发症。方法　移植治疗 3例高风险SAA。预处理 :抗淋巴细胞球蛋白 (ALG)联合环磷酰胺 (CTX) ,CTX总量为 60～ 12 0mg/kg ,ALG为 12 0mg/kg。移植物抗宿主病 (GVHD)的预防 :环孢素A(CSA)联合甲氨蝶呤 (MTX)或甲基强的松龙 (MP) ,CSA和MP分别用至 6个月和 2个月逐渐减量并停药。供者外周血造血干细胞 (PBSC)动员 :G -CSF 5 μg/ (kg·d)× 5d。移植细胞数分别为MNC :7 2 4× 10 8/kg ,6 0 0× 10 8/kg ,6 66× 10 8/kg ;CD3 4+ 细胞 :4 2 6×10 6/kg ,8 95× 10 6/kg ,4 66× 10 6/kg。移植后形成混合性嵌合体 (MC)者 ,进行DSI。结果　移植后 3例白细胞最低值 :0 2 6× 10 9/L ,0 5 0× 10 9/L ,0 10× 10 9/L ,中性粒细胞 >0 5× 10 9/L和血小板 >2 0× 10 9/L时间分别为移植后第 12 ,3 ,15天和 0 ,5 ,10天。 3例均获得造血细胞成功植入。 1例形成供者完全嵌合体 (CC)并长期维持造血。 2例MC者 ,1例出现排斥 ,1例巨核细胞植入不良 ,均经DSI ,造血均有恢复。 3例分别存活 10 ,6,3 4个月。结论　非清髓性骨髓联合外周血高剂量造血干细胞移植治疗高风险的SAA ,增加植入率、减少     

Bone marrow transplantation in aplastic anaemia

This report describes a case of aplastic anaemia who underwent bone marrow transplantation from an ABO compatible HL-A identical sibling of opposite sex. Engraftment was observed with transient recovery of haematopoietic function and documentation of donor type sex chromosome patterns in the recipient’s marrow cells. The patient died 35 days posttransplant. The transplantation protocol used and the potential for marrow allografts in bone marrow failure are discussed.     

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.     

骨髓NKT细胞活性与儿童再生障碍性贫血相关性研究

目的 探讨骨髓中自然杀伤T细胞(nature killer T cell, NKT)在再生障碍性贫血免疫介导发病机制中的作用。方法 选取14例确诊儿童再生障碍性贫血为再生障碍性贫血组,同年龄正常儿童10例为对照组。流式细胞术检测两组儿童骨髓中NKT含量;利用免疫磁珠法分离纯化NKT细胞后,分别在4种不同体系下进行扩增培养。A: α-Galcer＋rhIL-2;B: α-Galcer＋rhIL-2＋rhG-CSF;C: OCH＋rhIL-2;D: OCH＋rhIL-2＋rhG-CSF。测定NKT细胞在不同培养条件下的扩增倍数;利用酶联免疫斑点技术(Elispot)测定NKT细胞扩增活化后表达IFN-γ、IL-4的斑点形成细胞数(SFCs)。结果 再生障碍性贫血组骨髓中NKT百分率(0.827%±0.022%)明显低于对照组(1.033%±0.073%,Z=-3.810,P=0.000)。在各培养体系中,再生障碍性贫血组和对照组骨髓NKT均可明显扩增。在含有α-Galcer培养体系A和B中,再生障碍性贫血组及对照组NKT细胞的扩增能力均高于OCH体系C和D,差异有统计学意义(P＜0.01或P＜0.05)。在培养体系中加入rhG-CSF后,再生障碍性贫血组骨髓NKT细胞的扩增能力下降(P＜0.01),但表达IFN-γ的SFCs明显减少(P均＜0.01);而表达IL-4的SFCs明显升高(P均＜0.01)。结论 再生障碍性贫血患儿骨髓NKT的数量和功能均明显低于正常儿童。但再生障碍性贫血骨髓在接受细胞配体(OCH或α-Galcer)+rhIL-2+rhG-CSF作用后,在获得NKT细胞一定程度扩增的同时,提高NKT的IL-4表达,降低NKT的IFN-γ表达,抑制T细胞向Th1分化,而促进T细胞向Th2分化,逆转再生障碍性贫血Th1/Th2异常失衡的免疫介导致病机制,可能成为获得性再生障碍性贫血的有效治疗途径。     

Treatment of severe aplastic anemia: comparison of bone marrow transplantation to immunotherapy

Between February 1985 and May 1988, sixteen patients with severe aplastic anemia (SAA) post multitransfusion were treated with either allogeneic bone marrow transplantation (BMT) (9) or immunosuppression (7). The latter group was further divided into two subgroups: horse anti-human thymocyte-lymphocyte globulin (ATG-ALG) (2) and high dose methylprednisolone (HDMP) (5). There were 8 males and 8 females, age ranged from 10 to 35 years for the BMT group and 19 to 56 for the immunosuppression group. As of analysis, 9 patients in the BMT group had been followed from 1 to 31 months after transplant (median,24). Graft rejection was noted in 2, both had positive mixed lymphocyte culture (MLC) index. Seven had full recovery of hematopoiesis. Of these 7 survivals, none developed acute graft-versus-host disease (GVHD), whereas 2 had chronic GVHD which resolved completely after a 9-month treatment with azathioprine and prednisolone. Kaplan-Meier survival probability at 31 month was 75%. In the immunosuppressive therapy group 2, who received ATG-ALG both failed the treatment, died 7 and 29 months later, respectively. There were 3 responders in the HDMP subgroup, 1 complete, 2 partial. The 1-year survival probability for this group was 42.9% compared with 75% in the BMT group (p greater than 0.10). However, the hematologic reconstitution and Karnofsky performance were complete in all 7 transplant survivals vs one of 3 in the immunosuppression group (p less than 0.01). This experience supports that for patients with SAA under the age of 40, BMT is the treatment of choice if an HLA-identical MLC-nonreactive marrow donor is available, if not, immunosuppression is an alternative approach.(ABSTRACT TRUNCATED AT 250 WORDS)     

泊沙康唑治疗重型再障造血干细胞移植后侵袭性真菌感染1例

<正>具有广谱抗真菌作用的第二代三唑类药物泊沙康唑,指南推荐用于接受异基因造血干细胞移植(allo-HSCT)患者侵袭性真菌感染(IFIs)的预防。但我们在临床上发现泊沙康唑亦适用于IFI的治疗。在此报道一例泊沙康唑成功治疗重症再生障碍性贫血(SAA)异基因造血干细胞移植后侵袭性真菌感染的病例。患者,女性,25岁,2013年8月确诊为急性重型再生障碍性贫血(VSAA),2013年12月行HLA(人     

再生障碍性贫血患者骨髓组织中微血管密度计数的临床意义

目的 :探讨再生障碍性贫血 (简称再障 )患者骨髓组织中微血管密度 (MVD)计数的临床意义。　方法 :对 30例再障、2 0例正常人、2 0例增生性贫血分别用苏木精 伊红 (H E)染色和CD34免疫组化S P法检测骨髓中MVD ,并检测各自造血组织面积所占百分数。　结果 :正常人骨髓CD34和H E染色MVD无明显差异 (P >0 .0 5 ) ;再障患者骨髓CD34和H E染色MVD无明显差异 (P >0 .0 5 ) ;再障患者病情轻、重者MVD比较有差异 (P <0 .0 5 ) ;增生性贫血患者H E染色和CD34标记染色所得MVD ,二者比较有差异 (P <0 .0 5 ) ;正常人、再障、增生性贫血三者骨髓经CD34染色MVD两两比较均有显著性差异 (P <0 .0 5 ) ,而且与骨髓造血组织面积所占百分数成正相关 (r =0 .74 ,P<0 .0 5 )。　结论 :CD34染色显示骨髓血管内皮细胞时 ,其特异性较高 ;MVD对临床判断再障的病情进展和预后有一定的意义 ;再障时 ,骨髓微血管受损伤 ,微血管数量减少。通过促进再障患者骨髓中微血管增生 ,改善骨髓的血供 ,从而诱导造血组织增生 ,可能会对再障的治疗开辟一条新的道路。     

Bone marrow transplantation.

Over the last 20 years allogeneic bone marrow transplantation from an HLA-identical sibling donor has become the treatment of choice for a number of human haematological malignancies, severe aplastic anaemia, some congenital diseases of the immune and haemopoietic systems, and some inborn errors of metabolism. Recently, the successful introduction of HLA-matched unrelated donor transplants, convenient T cell depletion technology, combination immunosuppressive therapy to minimise graft-versus-host disease, blood products that are seronegative for cytomegalovirus, effective antiviral agents, and cloned haemopoietic and immune system growth factors have markedly increased the scope of bone marrow transplantation. Additionally, autologous transplantation appears to have promise especially in lymphoma and breast cancer.     

再生障碍性贫血骨髓病理分型研究

目的:研究再生障碍性贫血骨髓病理分型与临床诊疗间的关系。方法:用不脱钙的塑料包埋法,制成2μm厚的骨髓病理切片,用网形测微器计点法测定切片内造血主质与脂肪组织所占容量的百分比率,确定骨髓增生度;以骨髓增生度、局限性造血细胞灶或岛、巨核细胞数等为再生障碍性贫血的骨髓病理分型依据。结果:在380例/次再生障碍性贫血骨髓病理检查患者中,依据此方法分型,其中:再生不良型83例(21.84%),再生障碍型II196例(51.58%),再生障碍型I101例(26.58%);提出再生障碍性贫血骨髓病理与低增生骨髓象、低增生骨髓增生异常综合征的鉴别特征。结论:对再生障碍性贫血患者,用不脱钙的塑料包埋法进行骨髓活检以及骨髓病理分型,可有效的指导患者的临床诊断和治疗。     

Magnetic resonance imaging of the bone marrow in 3 patients with aplastic anemia

Bone marrow appearances in aplastic anemia are characterized by the abundance of fatty marrow that replaces normal functional marrow. The signal intensity of aplastic bone marrow in sagittal T1-weighted magnetic resonance images of the spine is bright, resembling that of subcutaneous fat and, in most cases, is not difficult to differentiate from normal age-related marrow changes. Three patients with aplastic anemia are described, and the correlation of magnetic resonance imaging of the spine with bone marrow trephine biopsy findings in these patients is portrayed. Magnetic resonance imaging is an accessible, non-invasive technique that allows sampling of a larger volume of bone marrow tissue and is especially useful in the detection of fatty marrow replacement of the normal functional marrow in aplastic anemia.     

Bone marrow transplantation in Canada.

Bone marrow transplantation is an established form of therapy for aplastic anemia and severe combined immunodeficiency. It is also a therapeutic option for acute leukemia in remission. Unfortunately, compatible donors are not available for most patients who could benefit from it. Further refinement of the techniques involved may make it suitable for more patients. Graft rejection, recurrent leukemia, graft-versus-host disease and interstitial pneumonia continue to be the main unsolved complications of bone marrow transplantation, but recent advances have decreased their frequency and severity. Most of the complications of allogeneic bone marrow transplantation may be eliminated with the use of autologous stem cells. For further refinement bone marrow transplantation should continue to be performed in large centres that combine treatment with research.