Selective depletion of marrow-T cytotoxic lymphocytes (CD8) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation

In vitro depletion of mature pan-T lymphocytes has been widely and successfully used to prevent acute graft-versus-host disease (GVHD) after allogeneic bone-marrow transplantation (BMT). However, this procedure has been associated with a high incidence of graft failure and leukemic relapse. In this pilot study, we evaluated the efficiency of a selective depletion of human marrow T cytotoxic lymphocytes (CD8), a subset essential to induce GVHD in mice. Eleven patients with hematologic malignancies were included (7 HLA-matched BMT, 4 HLA-mismatched BMT). Marrow treatment with 7 anti-CD8 mAbs and rabbit complement resulted in a marked reduction of CD8+lymphocytes from 15% (median value; range 7%–31%) to 1% (median value; range<1%–11%). Acute GVHD was not abolished by this procedure despite postgraft immunosuppression. One patient (HLA-mismatched BMT) rejected his graft and had a full autologous recovery. In conclusion, when compared to the data in the literature, CD8 depletion was shown to be less efficient than pan-T-cell depletion in the prevention of GVHD after allogeneic BMT and was still associated with a major complication associated with this procedure, i.e., graft failure.     

Characterization of peripheral blood T-cell subpopulation of bladder cancer patients

Summary The levels of immune reactivity of peripheral and blood T-lymphocytes were evaluated in 37 bladder cancer patients and 31 age-matched controls. T-lymphocyte subsets were quantified by monoclonal antibodies, and the immune reactivity was measured using stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM). Comparing the patients before and after treatment revealed significant changes in the stimulation index of proliferative response to PHA, PWM, in the PWM% (the patient response compared to the control), and in the percent of T8 cells from the total count of blood lymphocytes. Further significant differences were found among the disease stages in the numbers of T3, T4 lymphocytes subpopulations and the total lymphocyte count. A significant interaction was found between the treatment and patient's sex regarding the T4:T8 ratio.Also, a higher prevalence of T4:T8<1 was found among the patients compared to the controls before and after treatment regardless of the disease stage. This T4:T8<1 ratio can serve as an indicator of immune competence in bladder transitional cell carcinoma patients.     

HLA单倍体相合与全相合外周血造血干细胞移植治疗恶性血液病的疗效比较

目的 观察和比较亲属间人类白细胞抗原(HLA)单倍体相合与全相合外周血造血干细胞移植(PBSCT)治疗恶性血液病的临床疗效.方法 2004年5月至2009年2月,共111例恶性血液病患者进行了异基因PBSCT(allo-PBSCT),其中单倍体相合移植受者51例(单倍体组),同期全相合移植受者60例(全相合组).两组的预处理方案均为清髓性;两组预防移植物抗宿主病(GVHD)均以经典环孢素A加短程甲氨蝶呤作为基础方案,HLA 1个抗原不合时,加用吗替麦考酚酯,HLA 2～3个抗原不合时,再加用抗胸腺细胞球蛋白(ATG)及抗CD25单克隆抗体.移植物为经粒细胞集落刺激因子动员的、未进行体外去除T淋巴细胞的外周血造血干细胞(PBSC).结果 111例受者均获得完全、持久供者干细胞植入.单倍体组和全相合组受者中性粒细胞≥0.5×10~9/L的中位时间分别为14 d和12 d,血小板≥20×10~9/L的中位时间分别为15 d和13 d.单倍体组有25例受者发生急性GVHD(aGVHD),其中Ⅰ度20例,Ⅱ度5例;有33例发生慢性GVHD(cGVHD),其中局限型30例,广泛型3例;4年累积发病率为70.4%;无白血病存活40例,3年预期总无白血病存活率(LFS)为74.5%,其中标危型77.3%,高危型68.2%.全相合组有14例发生aGVHD,其中Ⅰ度10例,Ⅱ度2例,Ⅲ度2例;有37例发生cGVHD,其中局限型32例,广泛型5例;4年累积发病率为58.1%.无白血病存活46例,3年预期总LFS为72.1%,其中标危型77.6%,高危型52.7%.单倍体组受者移植后aGVHD发生率高于全相合组,差异有统计学意义(P<0.05);但cGVHD、原发病复发率和LFS差异均无统计学意义(P>0.05).结论 应用清髓性预处理联合多种免疫抑制剂进行非体外去T淋巴细胞的、亲属间HLA单倍体相合与全相合PBSCT均为治疗恶性血液病安全有效的方案.     

ABO血型不合对同胞异基因外周血干细胞移植的影响

目的探讨HLA配型相合但ABO血型不合的同胞异基因外周血干细胞移植(allo- PBSCT)治疗血液恶性肿瘤的疗效。方法对2001年6月至2005年9月的68例HLA配型相合的血液恶性肿瘤患者进行同胞allo-PBSCT,其中ABO血型不合30例(血型不合组),ABO血型相合38例(血型相合组)。急性髓细胞白血病(AML)、骨髓增生异常综合征(MDS)和慢性粒细胞白血病(CML)患者采用马利兰(BU)/环磷酰胺(CY)预处理方案；急性淋巴细胞白血病(ALL)和非霍奇金氏淋巴瘤(NHL)患者采用全身照射(TBI)/CY方案；多发性骨髓瘤(MM)患者采用TBI/CY/马法兰方案。移植物抗宿主病(GVHD)的预防采用霉酚酸酯(MMF)、环孢素A(CsA)和短程甲氨喋呤(MTX)三联方案。结果(1)除1例植入失败外,其余67例患者全部造血重建。中性粒细胞绝对值≥0．5×10~9/L和血小板数≥20×10~9/L的平均时间为移植后+12(+9～+15)d和+21(+15～+40)d,血型不合组与血型相合组植入的时间差异无统计学意义(P＞0．05)。(2)血型不合组均未出现急性溶血反应,但与血型相合组比较,红系造血延迟,在供/受者血型为A/O的7例患者中有3例(42．9%)发生纯红细胞再生障碍性贫血(PRCA)。血型不合组于移植后60d(24～153 d)血型成功转变为供者型。(3)随访至2005年9月30日,血型不合组急性GVHD发生率(20．0%)比血型相合组(2．6%)高(P=0．019),但慢性GVHD发生率、肝静脉栓塞综合征(VOD)发生率、巨细胞病毒(CMV)感染发生率、出血性膀胱炎(HC)发生率、疾病复发率及死亡率与血型相合组比较,差异无统计学意义(P＞0．05)。(4)用Kaplan-Meier生存分析发现,血型相合组和血型不合组患者之间预期4年的生存率差异无统计学意义(P＞0．05)。结论ABO血型不合可以进行allo-PBSCT,并且不影响干细胞移植的植活,虽然急性GVHD的发生率较血型相合组高,但其对复发率、死亡率及生存率无显著影响。     

Monitoring of cardiac graft recipients: comparison of in vivo activated,committed T lymphocytes in peripheral blood and in the graft

The proliferative and cytotoxic capacity of peripheral blood lymphocytes (PBL) and the cytotoxic activity of lymphocytes propagated from endomyocardial biopsies (EMB) towards donor cells was used to identify in vivo activated, committed T cells. A series of 39 PBL samples and 38 EMB simultaneously taken from 20 patients after heart transplantation was cultured in interleukin 2 (IL-2) conditioned medium. The cytotoxic capacity of these cultures against donor cells was tested in a 4-h chromium-51 release assay. From a comparable patient group, 224 samples were evaluated for donor reactivity by a primed lymphocyte test (PLT). Analysis showed that PBL cultures hardly ever contained committed cytotoxic T lymphocytes (cCTL, 2/39) or committed proliferative T lymphocytes (cPTL, 1/224). In contrast, significantly more EMB cultures (17/38, P < 0.001, χ² test) demonstrated donor-directed cytotoxicity. This was especially found during rejection (11/17 vs 6/21 without rejection, P = 0.05). These results show that after heart transplantation, committed cells are mainly found in the graft.     

自体外周血单个核细胞移植治疗下肢缺血53例的临床研究

目的观察自体外周血单个核细胞移植治疗下肢缺血的有效性和安全性。方法2004年6月至2005年10月，采用自体外周血单个核细胞移植治疗53例（83条下肢）下肢严重缺血。病因为糖尿病性下肢缺血44例71条患肢（44／53，83．0％）；单纯性下肢动脉硬化5例6条患肢（5／53，9．4％）；血栓闭塞性脉管炎4例6条患肢（4／53，7．6％）。本组患者中80．7％（67／83）患肢有疼痛感，72．3％（60／83）肢体有冷感，67．5％（56／83）肢体有麻木感。移植后2个月评估其疗效。结果本组无死亡病例。移植后2个月总的疼痛缓解率为83．6％，总的冷感缓解率为91．7％，总的麻木缓解率为75．0％。有39．8％（33／83）患肢的ABI有所增加。89．2％（74／83）患者经皮测定的氧分压（TePO2）有不同程度的增加。29．2％患者的溃疡面有不同程度的缩小。有44．6％（23例37条）于术后行血管造影评估，其中72．9％患肢有不同程度的侧支血管形成。15条（18．1％）患肢最终行截肢，其中5条患肢降低了截肢平面。结论自体外周血单个核细胞移植治疗下肢缺血性疾病是一种简单、安全、有效的方法；在治疗过程中需要注意心脑血管并发症的发生。     

泡状棘球蚴感染对大鼠免疫学状态及移植心存活的影响

目的 研究肝泡状棘球蚴感染对大鼠免疫学状态及移植心存活的影响。方法 建立SD大鼠到Wistar大鼠的颈部异位心脏移植模型。对照组以未接种泡状棘球蚴的Wistar大鼠为受者；实验组以感染泡状棘球蚴的Wistar大鼠为受者。术后观察移植心的存活时间、组织病理学变化、心肌组织内T淋巴细胞和嗜酸粒细胞的浸润情况，测定血清内白细胞介素4（IL-4）和γ干扰素（IFN-γ）水平。结果实验组移植心的存活时间与对照组相比，差异有统计学意义（P〈0．05），组织病理学分级及心肌组织中CD4^＋T淋巴细胞数与对照组相比，差异无统计学意义，而CD8^＋T淋巴细胞数、嗜酸粒细胞数与对照组相比，差异均有统计学意义。发生排斥反应时，实验组血清内IL-4水平高于对照组，而IFN-γ水平低于对照组。结论 泡状棘球蚴感染造成TH1／TH2向TH2类细胞因子偏移，有利于移植物的存活，嗜酸粒细胞浸润可能是移植心发生排斥反应的原因之一。     

异基因外周造血干细胞移植治疗极重度骨髓型急性放射病一例

目的探讨异基因外周血造血干细胞移植治疗极重度骨髓型急性放射病的效果，积累临床经验。方法1例患者意外受60^Co照射，受照射剂量为9～15Gy，诊断为极重度骨髓型急性放射病，在受照射后第4天患者开始接受预处理，3d后进行了HLA全相合的异基因外周造血干细胞移植。移植后采用环孢素A和霉酚酸酯预防移植物抗宿主病（GVHD）。结果造血功能于移植后第9天开始恢复，第11天WBC升至14．74×10^9L，随后降至正常范围，血小板升至50×10^9／L，Hb在80g／L以上。经短串联重复序列聚合酶链反应及血型动态检测，证实供者细胞稳定植入，原有染色体畸变和微核均消失，血型于移植后第27天完全转变为供者型。患者未发生GVHD，但放射性损伤持续加重，并发多重感染，于移植后第68天（受照射后第75天）死于多脏器功能衰竭。结论极重度骨髓型急性放射病可以通过异基因造血干细胞移植恢复造血功能，为患者存活创造机会，但仅有造血功能恢复，而未能解决好放射线对全身组织的损伤及免疫功能重建，患者仍难长期存活。     

Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation

Abstract Cellular mechanisms may play a role in the development of graft vascular disease (GVD). We previously demonstrated that GVD correlated with an increase of donor-specific T-helper 1 cytokine production by graft-infiltrating lymphocytes but not by peripheral blood mononuclear cells (PBMC). These T-helper 1 cytokines aid the generation of cytotoxic T-lymphocytes (CTL). In the present report, we investigated whether there is a relationship between the frequency of donor-specific CTL precursors (pCTL) in PBMC and the development of GVD. We tested PBMC samples of five patients with GVD and five patients without GVD in the periods 3–6 months, 1 year, and 3 years after heart transplantation. At all time points, GVD was not related to the number of pCTL. In conclusion, donor-specific cellular tests in peripheral blood could not be related to GVD. Apparently, donor-specific reactions associated with the induction of GVD can only be monitored in the graft.     

Paclitaxel saves rat heart allografts from rejection by inhibition of the primed anti-donor humoral and cellular immune response: implications for transplant patients with cancer

Paclitaxel is an anti-neoplastic drug that was recently shown also to have immunosuppressive properties in naïve rat heart transplant recipients. Here, we tested whether paclitaxel could also effectively reverse an ongoing immune response in transplant recipients. We therefore used a model in which Lewis rat recipients receiving ACI rat heterotopic heart allografts were: (1) untreated, or treated with either (2) paclitaxel or (3) cyclosporine, starting 5 days after transplantation. Allograft survival was determined in one group, and in a second group cytotoxic T-lymphocyte (CTL) responses were determined and serum anti-donor cytotoxic antibody levels were measured. Results showed that paclitaxel was as effective as cyclosporine in saving recipients from imminent allograft rejection. Immunologically, paclitaxel reduced the allogeneic-CTL response, but most impressively, the cytotoxic antibody response was nearly eliminated in saved recipients. Therefore, paclitaxel's immunosuppressive properties, along with its known effectiveness against a wide variety of tumors, makes it potentially useful for the simultaneous treatment of rejection and neoplasms in cases of transplant-related cancer.     

Selective depletion of marrow-T cytotoxic lymphocytes (CD8) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation

Abstract. In vitro depletion of mature pan-T lymphocytes has been widely and successfully used to prevent acute graft-versus-host disease (GVHD) after allogeneic bone-marrow transplantation (BMT). Hpwever, this procedure has been associated with a high incidence of graft failure and leukemic relapse. In this pilot study, we evaluated the efficiency of a selective depletion of human marrow T cytotoxic lymphocytes (CD8), a subset essential to induce GVHD in mice. Eleven patients with hematologic malignancies were included (7 HLA-matched BMT, 4 HLA-mismatched BMT). Marrow treatment with 7 anti-CD8 mAbs and rabbit complement resulted in a marked reduction of CD8 + lymphocytes from 15% (median value; range 7%-31%) to 1% (median value; range <1%-11%). Acute GVHD was not abolished by this procedure despite postgraft immunosuppression. One patient (HLA-mismatched BMT) rejected his graft and had a full autologous recovery. In conclusion, when compared to the data in the literature, CD8 depletion was shown to be less efficient than pan-T-cell depletion in the prevention of GVHD after allogeneic BMT and was still associated with a major complication associated with this procedure, i.e., graft failure.     

冷冻消融治疗软组织肉瘤后外周血T细胞亚群变化与患者生存期的相关性

目的 观察冷冻消融治疗软组织肉瘤(STS)后外周血T细胞亚群变化及其与患者生存期的相关性。方法 纳入22例接受冷冻消融治疗的晚期STS患者,比较治疗前、后外周血T细胞亚群变化,分析影响患者生存期的相关因素,以及总生存期(OS)和无进展生存期(PFS)与外周血T细胞亚群变化的相关性。结果 共对22个病灶实施冷冻消融。治疗后疾病客观缓解率为81.82%(18/22),患者中位OS为15个月,中位PFS为7个月。OS与肿瘤病理分级和消融效果相关(P均<0.01)。治疗后外周血CD4⁺T、Treg细胞较治疗前降低、自然杀伤(NK)细胞较前升高(P均<0.05);患者PFS与NK细胞水平呈正相关(r=0.539,P=0.010),OS与Treg细胞水平呈负相关(r=-0.463,P=0.030),PFS则与治疗前、后外周血CD4⁺T细胞差值呈正相关(r_s=0.424,P=0.049)。结论 冷冻消融治疗STS可在一定程度上改善机体免疫功能;治疗后血清NK、Treg细胞水平可用于评估患者生存期。     

Comparison of osteoclast precursors in peripheral blood mononuclear cells from rheumatoid arthritis and osteoporosis patients

Osteolytic disorders cause serious problems for quality of life with aging. Osteolysis is performed by osteoclasts of the hematopoietic lineage that share some characteristics with monocytes and macrophages. As osteoclast precursors (pOCs) are present in peripheral blood, their characterization in osteolytic diseases may help us to understand risk factors. Although essential factors for osteoclastogenesis have been reported, the effective induction from pOCs in human peripheral blood mononuclear cells (PBMCs) to mature osteoclasts in culture requires further improvement. The aim of this study was development of an efficient culture system for human osteoclastogenesis and providing a simple system for the enrichment of pOCs from PBMCs. We employed coculturing of human PBMCs with a mouse stromal cell line. Significant numbers of tartrate-resistant acid phosphatase-positive (TRAP⁺) multinucleated osteoclasts (MNCs), which could resorb dentine slices, were efficiently induced in this culture condition. pOCs were enriched in an anti-CD16 antibody column-passed anti-CD14 antibody-bound cell population isolated by magnetic cell sorting. We compared the percentage of the CD14^high CD16^dull cell population, which mainly contained pOCs in PBMCs, from age-matched patients with rheumatoid arthritis (RA) and osteoporosis (OP), but it was comparable. However, the mean number of TRAP⁺ MNCs generated in cultures from PBMCs of RA was higher. In contrast, the frequency of pOCs in PBMCs from OP was relatively higher. These results suggest the characteristics of pOCs from RA and OP may be different, because single pOCs from OP gave rise to lower numbers of osteoclasts than those from RA.     

Intragraft events after heart transplantation: an experimental study comparing cytology in coronary sinus blood,peripheral blood,and daily histology

Acute rejection is a frequent consequence after heart transplantation. To expand our knowledge of the rejection process and to investigate some intragraft events during acute rejection, the following experimental transplantation model was designed. Right cervical heart transplantation was performed in 12 mongrel dogs. Two experimental groups of six animals each received different immunosuppressive regimens. All animals were treated with daily triple drug therapy. In contrast to group 1, the animals in group 2 received high-dose steroids during rejection. The condition of the hearts was examined by daily transmural biopsies, graded according to the Billingham classification. To detect and quantify alterations in the mononuclear cell subsets of the myocardial venous return, blood samples from the coronary sinus blood (CS) and from peripheral blood (PB) were taken simultaneously with the biopsy. The total number of lymphoblasts and activated lymphocytes was determined and an activation index (AI) was calculated. The data referred to was established from 337 transmural biopsies. The AI of PB (n=287) correlated well with the different stages of acute rejection (grade B0: AI=2.2±2.1; grade B1+2: AI=6.3±1.7; grade B3: AI=10.0±4.7; P<0.001). The rejection kinetics of both groups, including the rejection-free interval following high-dose steroid administration in group 2, could be expressed accurately by the AI. The time course of the total number of lymphoblasts in CS versus PB demonstrated that the lymphoproliferative response started 4 days prior to the first intramyocardial signs of rejection (x = 3.8 ± 0.7; n=12). The maximum number of lymphoblasts was seen on the day of rejection in group 1 and 1 day after the onset of histologically proven rejection in group 2 (group 1: n=6: CS x = 40.1 ± 7.5; PB x = 12.2 ± 4.1; P<0.001; group 2: n=6: CS x = 39.4 ± 8.8; PB x = 12.9 ± 3.7; P<0.001). Under rejection therapy in group 2 these cells decreased immediately, followed by a short rejection-free interval. In group 1 the total number of lymphoblasts diminished continuously, almost reaching the nuber in PB at the time of final rejection. In contrast, activated lymphocytes did not render adequate results. Comparison of daily histology and the data of PB proved there is a good correlation between the AI and the different histologic stages of acute rejection. The total number of lymphoblasts in CS during rejection is significantly higher than in PB. Acute rejection seems to be detectable almost 4 days before histology and PB cytology by cytologic evaluation of the CS. Therefore, we speculate that the differentation and proliferation of lymphoblasts during the initial phase of acute rejection takes place within the graft itself.     

HOE-642联合改良K/Mg冷血心麻液对犬供心的保护作用

目的探讨HOE-642联合改良K／Mg冷血心麻液提高犬供心的保存效果的作用。方法雄性成年杂种家犬32只，随机分为整合组和常规组（每组16只，供、受者各8只）。（1）整合组：供心保护采用HOE-642联合改良K／Mg冷血心麻液的“整合策略”；（2）常规组：供心保护采用临床上常规方法。所有动物的供心均冷浸浴保存4h，心脏移植用原位标准法。记录不同时段的心功能指标；实验结束后观察心肌超微结构并测定心肌含水量。结果每组各1例主动脉开放后因主动脉吻合口漏血，失血陛休克死亡，剔除出实验；其余动物均成功脱离体外循环。整合组的移植心脏左心室收缩功能和舒张功能恢复指标显著优于常规组（P〈0．05）；整合组心肌组织含水量显著小于常规组（P〈0．05）；整合组心肌细胞亚细胞结构的保存亦优于常规组。结论临床常规方法和HOE-642联合改良K／Mg冷血心麻液的“整合策略”，均可安全冷保存供心4h，但后者能进一步减轻心肌水肿、维持心肌细胞结构完整、促进缺血／再灌注损伤后心功能的恢复，具有更佳的心肌保护效果。     

肝移植围手术期外周血单个核细胞内乙型肝炎病毒DNA的检测及临床价值

目的 观察肝移植围手术期外周血单个核细胞(PBMC)内乙型肝炎病毒(HBV)DNA的变化规律,探讨其在监测肝移植受体体内HBV存在及活动状态中的价值.方法 2007年8月至2007年12月20例乙肝表面抗原(HbsAg)阳性肝移植受体给予口服恩替卡韦联合肌注乙肝免疫球蛋白(HBIG)作为HBV再感染的预防方案,分别于术前1 d、术后1周、4周、12周采用实时荧光定量PER法检测血清HBV DNA、PBMC内HBV DNA.结果 术前1 d、术后1周、4周、12周PBMC内HBV DNA阳性率分别为85.0%(17/20)、45.0%(9/20)、45.0%(9/20)和40.0%(8/20),术后1周与术前比较差异有统计学意义(P<0.01),但1周以后阳性率无显著变化;围手术期PBMC内HBVDNA定量均值分别为104.07±2.07、101.69±1.96、101.15±1.72和101.30±1.63拷贝/106细胞,同样术后1周与术前比较差异有统计学意义(P<0.01),但随术后时间的延长,下降趋势越来越缓慢,术后4周后定量值的下降差异无统计学意义.各时间点血清HBV DNA阳性率分别为70.0%(14/20)、25.0%(5/20)、5.0%(1/20)和0;血清HBVDNA定量均值分别为103.27±2.54、100.91±1.63、100.23±0.98和0拷贝/106细胞.结论 肝移植术后PBMC内HBV DNA迅速转阴并维持在同一稳定水平.PBMC内HBV DNA定量检测似乎较血清HBV DNA能更好的反映肝移植围手术期体内残存病毒的存在及活动状态.     

CD4+ and CD8+ T cell subset distribution in the blood of small-bowel-grafted rats: modification during graft-versus-host disease

Abstract We studied the modifications of blood T cell distribution following small-bowel allografting in rats under different experimental conditions. Group 1: ACI (RT1^a) rats were used as small-bowel donors for ACI × Wistar (RT1^y) F₁, hybrid rats (WAF₁) in which graft-versus- host disease (GVHD) developed. Group 2: WAF₁ rats were used as small bowel donors to ACI rats which developed rejection. Group 3: WAF₁ rats received small bowel from ACI rats hyperimmunized for 10 days (by grafting them with WAF₁ skin) and GVHD developed. Group 4: Wistar rats received small bowel from ACI rats hyperimmunized for 10 days (by Wistar skin) and bidirectional GVHD and rejection were assured. A second set of the same groups which were continuously administered with cyclosporin (15 mg/kg per day s.c. for 15 consecutive days) was also studied. Recipient peripheral blood lymphocytes, obtained at 7 and 15 days following small-bowel transplantation, were stained with monoclonal antibodies anti-rat CD4 and CD8 and then analyzed in an automated flow cytometer. A significant major reduction of CD4⁺/CD8⁺ T cell ratios was shown in rats that developed simultaneous GVHD and rejection with respect to ungrafted rats.     

亲缘单倍体相合外周血造血干细胞移植治疗重症再生障碍性贫血

【摘要】目的探讨改良白消安／环磷酰胺＋抗胸腺细胞球蛋白（Bu／Cy＋ATG）预处理方案在亲缘单倍体造血干细胞移植治疗重症再生障碍性贫血（SAA）临床应用中的有效性和安全性。方法回顾分析河北唐山钢铁集团有限责任公司医院血液肿瘤科自2009年10月至2011年5月间采用亲缘单倍体外周血干细胞移植治疗的3例SAA患者资料。供者均为母亲,1例HLA3／6位点相合,2例HLA4／6位点相合。预处理方案均为改良Bu／Cy＋ATG,具体为白消安0．8m∥kg,每天4次,连用2d;环磷酰胺50mg·kg-1·d-1,连用4d;抗胸腺细胞球蛋白2．5mg·kg-1·d-1,连用4d。环孢素＋短程甲氨蝶呤＋吗替麦考酚酯预防排斥反应。结果3例患者均达完全供者植入,2例合并Ⅱ-Ⅲ度急性移植物抗宿主病（GVHD）,1例患者合并局限型慢性GVHD。3例患者均发生血CMV感染,经抗病毒治疗均得以控制。随访5～25个月,3例患者至今均无病存活。结论初步经验Bu／Cy＋ATG预处理方案经改良用于亲缘单倍体外周血造血干细胞移植治疗SAA安全、有效。     

Frontal cerebral blood flow is impaired in patients with heart transplantation

Patients with cardiovascular disease have cognitive function disturbances that are still evident after heart transplantation (HT). The aim of this study was to evaluate cerebral function in transplant patients and to assess whether cyclosporine therapy was responsible for cerebral abnormalities 1 year after transplantation. Six HT patients, eight liver transplant (LT) patients, and ten age-matched healthy controls underwent regional cerebral blood flow (rCBF) assessment by the (99m)Tc-hexamethyl-propylene-amineoxime ((99m)Tc-HM-PAO) single-photon emission computed tomography (SPECT) technique. The rCBF was correlated with cyclosporine blood levels. rCBF in HT and LT patients was similar to that of controls in all regions assayed, except for the frontal inferior region of HT patients, where it was significantly lower than in controls. No correlations between rCBF and cyclosporine blood levels were found in either HT or LT patients. In conclusion, the cerebral abnormalities seen in patients after HT but not after LT may be due to long-standing cerebral hypoperfusion resulting from severe heart disease, whereas cyclosporine does not account for such functional alterations.     

丝列霉素处理的外周血单核细胞对大鼠同种异体移植心脏的影响

目的观察MMC处理的外周血单核细胞（PBMCs）对大鼠同种异体心脏移植的影响。方法BN大鼠作为供体，Lewis大鼠作为受体，体重在200～300g。PBMCs于含有MMC的细胞培养液中培养30min后于移植前1周静脉注射人受体，然后接受心脏移植，观察移植心脏的存活情况；并利用FACS检测MMC对PBMCs存活率的影响。结果MMC处理过的PBMCs诱导了细胞的凋亡；接受MMC处理过的PBMC的大鼠，移植心脏的存活时间明显得以延长。结论MMC处理的PBMCs可以延长大鼠移植心脏的存活时间，对移植心脏的延长作用可能是由于MMC诱导了细胞的凋亡引起的。