Improved survival after bone marrow transplantation for early leukemia using busulfan-cyclophosphamide and individualized prophylaxis against graft-versus-host disease: a long-term follow-up

To minimize immunosuppression, allow a graft-versus-leukemia (GVL) effect, and reduce relapse incidence, 73 leukemic recipients of human leukocyte antigens-identical sibling marrow were given graft-versus-host disease (GVHD) prophylaxis based on the estimated risk of GVHD development. Methotrexate (MTX) monotherapy was given to patients with an estimated low risk of developing GVHD, whereas MTX + cyclosporine (CsA) was given to 'high-risk' patients. After engraftment, CsA was discontinued, and weekly MTX was reinstituted and given until 3 months post-bone marrow transplant. Conditioning consisted of busulfan (BU) + cyclophosphamide (CY) (n = 35) or CY + total body irradiation (TBI) (n = 38). Retrospective controls were given CY + TBI and MTX + CsA (n = 39). The median observation time was 5 yr 11 months. Chronic GVHD increased to 53% in the individual BU + CY group and 46% in the individual CY + TBI group, compared to 25% in the control group (p = 0.05). This increase was restricted to the limited form. The actuarial relapse incidence decreased to 20% in the individual BU + CY group, compared to 52% in the control group, p = 0.03. In the individual CY + TBI group, the relapse incidence was 44% (n.s. versus controls, p = 0.04 versus individual BU + CY). The 5-yr relapse-free survival (RFS) in the individual BU + CY group was 66%, in the control group, 41% (p = 0.07), and in the individual CY + TBI group, 45% (p = 0.1 versus individual BU + CY). Patients with early leukemia in the individual BU + CY group had a RFS of 83%, compared to 44% in the control group (p = 0.02) and 42% in the individual CY + TBI group (p = 0.01). In the multivariate analysis, advanced leukemia beyond first complete remission and first chronic phase and conditioning with CY + TBI were correlated to poor RFS. In summary, the individualized prophylaxis itself did not reduce the relapse incidence. However, in patients with early leukemia conditioning with BU + CY, our method of individualizing the GVHD prophylaxis might be of value, since this group had the best RFS in this study.     

英夫利西单抗治疗移植后肠道急性移植物抗宿主病的临床效果

目的 观察英夫利西单抗治疗异基因造血干细胞移植后发生肠道急性移植物抗宿主病(GVHD)的有效性和安全性.方法 北京军区总医院血液科于2012年1月至2015年1月应用英夫利西单抗治疗15例移植后发生肠道急性GVHD的患者,均为Ⅲ～Ⅳ度肠道GVHD,其中男9例,女6例,平均年龄28.8岁,5例为HLA配型全相合,10例为HLA配型不全相合,肠道GVHD发生的中位时间是移植后66.7d.英夫利西单抗治疗方法为每次5 mg/kg,1次/周,根据肠道GVHD控制情况应用1～4次.观察患者的有效性和输注相关毒副作用.结果 输注英夫利西单抗后患者总体不良反应较轻,7例肠道GVHD得到完全缓解,3例部分缓解,无效5例,总有效率为66.7％.随访至2015年1月,中位随访时间11.1个月.全部患者中5例死于肠道GVHD,3例患者死于复发,1例死于感染,其他患者仍处于完全缓解状态,无病生存率为40％,最长无病生存时间已达32个月.结论 英夫利西单抗治疗移植后肠道急性GVHD疗效显著,副作用小.     

Micafungin as antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: results of different dosage levels in clinical practice

Micafungin has been approved for the prophylaxis of Candida infections in patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Here, we report a single‐center experience of three different dose levels regarding efficacy, toxicity, and colonization with Candida ssp. in clinical practice. In total, 150 consecutive adult patients who underwent allo‐HSCT received micafungin at a dosage of 50, 100, or 150 mg once daily for primary antifungal prophylaxis. Of those patients receiving more than six d of micafungin prophylaxis, 12/46 (26%), 6/44 (14%), and 9/46 (20%) were switched to empiric antifungal treatment. The frequency of invasive fungal infections (IFIs) according to EORTC criteria did not differ significantly (7/46; 15% vs. 5/44; 11% vs. 5/46; 11%) across the different dosage groups. In the 50‐mg group, there was one case of candidemia with C. parapsilosis after 12 d of micafungin prophylaxis. In all three groups, micafungin prophylaxis was well tolerated without any case of toxicity‐related treatment discontinuation. Renal function was not significantly altered, while increase of bilirubin was mainly due to concomitant ATG application. The incidence of IFIs is similar irrespective of the micafungin dosage while there was a trend toward more frequent change to empiric antifungal treatment as well as oropharyngeal colonization with candida in the lowest dosage group.     

伊马替尼治疗慢性移植物抗宿主病2例临床分析

目的探讨伊马替尼治疗异基因造血干细胞移植(allo-HSCT)后慢性移植物抗宿主病(GVHD)伴嗜酸性粒细胞增多的疗效及嗜酸性粒细胞增多与慢性GVHD的关系。方法回顾性分析2例白血病患者allo-HSCT术后慢性GVHD的诊治经过并结合文献复习讨论。结果 2例患者分别于移植后5个月和76d出现口腔溃疡、皮肤瘙痒、皮疹、胆红素水平增高和转氨酶水平增高,伴有嗜酸性粒细胞增多,诊断为局限型慢性GVHD,激素治疗不佳,加用伊马替尼后症状缓解,嗜酸性粒细胞数降至正常,无不良反应。结论伊马替尼治疗慢性移植物抗宿主病安全、有效,嗜酸性粒细胞增多可能与GVHD有一定的关系。     

High frequency of CD4+ CD25- CD69+ T cells is correlated with a low risk of acute graft-versus-host disease in allotransplants

Regulatory T cells (Tregs) maintain transplantation tolerance and suppress graft-versus-host disease (GvHD) in humans. We monitored 17 subjects with acute GvHD to determine whether Treg frequency correlates with acute GvHD. We found the percent of CD4(+) CD25(-) CD69(+) Tregs decreases when acute GvHD develops and increases after acute GvHD is controlled. We next sequentially studied 50 subjects receiving conventional allotransplants. We show a high frequency and increased numbers of CD4(+) CD25(-) CD69(+) Tregs are associated with a reduced risk of acute GvHD. We also show that CD4(+) CD25(-) CD69(+) Treg numbers increase substantially early after allografts and that a low percent of CD4(+) CD25(-) CD69(+) Tregs is associated with an increased risk of acute GvHD. Reconstitution of Tregs early post-transplant is associated with less acute GvHD. These data imply that CD4(+) CD25(-) CD69(+) Tregs are a novel subset of regulatory T cells that may protect against acute GvHD after allotransplants.     

间充质干细胞防治慢性移植物抗宿主病：进展与挑战

慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植后的主要并发症,也是导致非复发死亡的主要原因,因其病理生理过程复杂,常规糖皮质激素联合免疫抑制药的防治有效率不足50%。对于糖皮质激素抵抗的cGVHD患者需启动二线治疗,然而目前的二线治疗方法尚未形成共识,且治疗效果不佳。间充质干细胞(MSC)是最常见的成体干细胞之一,因其具有多维度、多靶点的免疫调控功能,已被广泛应用于cGVHD的预防及治疗,且大量研究证实了MSC治疗cGVHD的安全性和有效性,有望成为cGVHD防治的新策略。本文主要围绕MSC防治cGVHD的研究进展、作用机制及存在的问题等方面进行综述,以期为今后优化MSC治疗方案、提高cGVHD防治效果提供新思路。     

Clinical relevance of endoscopy with histopathological assessment in children with suspected gastrointestinal graft-versus-host disease

Endoscopy with histopathological assessment is an established practice to confirm gastrointestinal graft-versus-host disease (GI-GVHD). However, the clinical relevance of this approach in children is incompletely evaluated. In a retrospective cohort study, we investigated the frequency of treatment changes in response to histopathological findings in all children (<18 years) in Sweden who underwent endoscopy for suspected GI-GVHD (2000-2013) after receiving hematopoietic stem cell transplantation. Sixty-eight children with ninety-one endoscopic occasions were enrolled. At the time of endoscopy, anti-GI-GVHD treatment was ongoing in 71% (65/91). In 18% (12/65) with ongoing treatment, no histopathological evidence of GI-GVHD or another cause to justify anti-GI-GVHD treatment was found. In 48% (44/91), endoscopy with histopathological assessment led to changes in the treatment regimen. Re-endoscopy was more frequent among those with treatment changes, versus unchanged treatment, 39% (17/44) and 13% (6/47), respectively (P = .007). Histopathological findings generating treatment changes were as follows: GI-GVHD in 68% (30/44), normal histology in 25% (11/44), and an alternative diagnosis in 7% (3/44). In conclusion, this study supports that endoscopy with histopathological assessment should be considered in all children with suspected GI-GVHD.     

Comprehensive analysis of the immunomodulatory effects of rapamycin on human T cells in graft-versus-host disease prophylaxis

Graft-versus-host disease (GVHD) is a major cause of toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). While rapamycin (RAPA) is commonly used in GVHD prophylaxis in combination with a calcineurin inhibitor (CNI), the understanding of its mechanism of action on human T cells is still incomplete. Here, we performed an extensive analysis of RAPA effects on human T cells in a humanized mouse model of GVHD, in ex-vivo T cell cultures and in patients given RAPA plus tacrolimus as GVHD prophylaxis after nonmyeloablative allo-HCT. We demonstrate that RAPA mitigates GVHD by decreasing T cell engraftment and differentiation, inhibiting CD8⁺ T cell activation and increasing the long-term IL-2 secretion, thereby supporting regulatory T cell (Treg) proliferation. In contrast, graft-versus-leukemia effects were not abrogated, as RAPA-treated T cells had increased resistance to apoptosis and retained their effector function and proliferative capacity upon re-stimulation. Importantly, we found that RAPA impact on Treg and CD8⁺ T cells was closely dependent upon IL-2 signaling and that therapeutic options interfering with IL-2, such as calcineurin inhibitors, antagonize the IL-2-dependent promotion of Treg mediated by RAPA. Our results suggest that RAPA immunological efficacy could be improved in combination with drugs having possible synergistic effects such as the hypomethylating agent 5-azacytidine.     

The safety and efficacy of acute graft‐versus‐host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL

Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft‐versus‐host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III‐IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II‐IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.     

PD-1 antibody and ruxolitinib enhances graft-versus-lymphoma effect without increasing acute graft-versus-host disease in mice

Boosting T cell immune response posttransplant with checkpoint inhibitors increases graft-versus-lymphoma (GVL) effects at the cost of increasing acute graft-versus-host disease (aGVHD). A combined targeted therapy is needed to decrease checkpoint inhibitors-induced aGVHD without impairing GVL. We studied whether this competition could be avoided by giving concurrent anti-PD-1 antibody and ruxolitinib in allotransplant mouse models in which recipients were challenged with A20 or EL4 lymphoma cells. Given alone the PD-1 antibody increased GVL but did not improve survival of recipients challenged with A20 cells because of increased deaths from aGVHD. Adding ruxolitinib decreased levels of effector T cells and related cytokines. Tbx21^- T cells had higher PD-1 levels compared with Tbx21⁺ T cells. Ruxolitinib increased PD-1 levels on donor T cells by suppressing Tbx21 expression. Ruxolitinib increased apoptosis of T cells which was reversed by the PD-1 antibody. PD-1 antibody preserved expression of granzyme B and cytotoxicity of T cells which were decreased by ruxolitinib. The net result of combined therapy was increased GVL, no increase in aGVHD and increased survival. The combined therapy improved survival of recipients challenged by A20 cells which expressed high level of PD-L1, but not EL4 cells which do not express PD-L1.     

利用脊柱骨来源骨髓细胞建立急性移植物抗宿主病模型

目的探讨利用脊柱骨来源骨髓细胞建立小鼠异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Allo-HSCT)急性移植物抗宿主病(aGVHD)模型的可行性。方法选择C57BL/6(H-2b)雄性小鼠为供体鼠,BALB/c(H-2d)雌性小鼠为受体鼠。制备供体鼠的脾细胞和脊柱骨来源骨髓细胞悬液。受体鼠采用药物加小剂量辐照的预处理方式,于移植前8d～移植前4d腹腔注射氟达拉滨(200mg/kg),接着移植前3d～移植前1d腹腔注射环磷酰胺(60mg/kg),最后在移植前进行全身照射(total-body irradiation,TBI),照射剂量为4Gy(戈瑞)。18只受体鼠经预处理后随机分为3组,每组6只:(1)骨髓移植组,只输入1×107个脊柱骨来源骨髓细胞;(2)aGVHD组,输注1×107个脊柱骨来源骨髓细胞和5×106个脾细胞,建立aGVHD模型;(3)空白对照组,不输入任何细胞。观察3组小鼠生存状态及存活率,取aGVHD组与骨髓移植组存活21d的受体鼠进行病理学检查,取aGVHD组移植后21～28d存活的小鼠的脾脏进行流式细胞术检测骨髓细胞嵌合度。结果骨髓移植组小鼠全部存活,可重建造血,单纯输注骨髓细胞不会诱发aGVHD。aGVHD组小鼠出现aGVHD表现,100%发生aGVHD相关死亡,中位生存期为18d;病理检查结果显示符合aGVHD病理表现,移植后21～28d存活的小鼠诊断为供受体混合嵌合状态,符合aGVHD诊断标准。结论用脊柱骨来源骨髓建立的aGVHD模型完全符合标准,且更加经济,适合大规模建模。     

急性移植物抗宿主病患者血浆中细胞因子的水平及其意义

目的探讨异基因外周血干细胞移植发生急性移植物抗宿主病(aGVHD)时血浆中相关细胞因子水平及其与aGVHD的关系。方法酶联免疫吸附法测定20例恶性血液病患者异基因外周血干细胞移植前后及发生aGVHD时的血浆白细胞介素18(IL-18)、白细胞介素2受体(IL-2R)、肿瘤坏死因子α(TNF-α)及白细胞介素10(IL-10)水平。结果所有患者的造血功能均获得重建；发生Ⅰ～Ⅱ度aGVHD者8例，Ⅲ～Ⅳ度aGVHD者3例；发生aGVHD者血浆IL-18及IL-2R水平显著高于无aGVHD者，且IL-18水平与aGVHD的严重程度呈正相关；TNF-α水平在移植前后无显著变化；发生aGVHD者的IL-10水平明显下降，而无aGVHD者则较移植前显著上升。结论来源于TH1细胞的Ⅰ类细胞因子和来源于TH2细胞的Ⅱ类细胞因子在aGVHD发生中具有相反作用。     

肝移植急性排斥反应的诊断与治疗

目的 总结肝移植术后急性排斥反应(AR)的诊治经验。方法 回顾性分析57例肝移植患者术后AR的发生率和治疗结果。结果 21例患者术后因肝功能异常而行38次移植肝活检(术后6～91d)，11例15次发生AR，其中8例为单次，3例为两次或两次以上，轻度11次，中重度4次，AR发生率为19．3％(11／57)。20次为单纯保存-再灌注损伤(PRI)。3次为药物中毒。所有AR均经激素冲击或调整FK506剂量后缓解。结论 移植肝活检对于AR的诊断与鉴别诊断有重要意义，只要给予及时的诊断与治疗，AR一般是可逆的。     

Antibiotic prophylaxis is not protective in severe acute pancreatitis: a systematic review and meta-analysis

Background

The use of prophylactic systemic antibiotics to prevent infection and reduce mortality in severe acute pancreatitis (SAP) remains a contentious issue. We assessed the clinical outcome of patients with SAP treated with prophylactic antibiotics compared with that of patients not treated with antibiotics.

Methods

We performed a systematic search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, using PubMed, Google Scholar, and Ovid as search engines without language restriction until the end of May 2008. We also manually searched the references of original/review articles and evaluated symposia proceedings, poster presentations, and abstracts from major gastrointestinal and surgical meetings. Relative risks were calculated for individual trials and data were pooled using a fixed-effects model. Relative risk (RR) reduction, absolute risk reduction, and number needed to treat were calculated and are reported with 95% confidence intervals.

Results

Results were subjected to sensitivity analysis to determine heterogeneity among studies. We pooled 502 patients from 8 studies. Patient age ranged from 43 to 59 years, and length of stay ranged from 18 to 95 days. There were 253 patients with SAP who received prophylactic antibiotics, and 249 patients were randomized to the placebo arm. Overall, there was no protective effect of antibiotic treatment with respect to mortality (RR, .76; 95% confidence interval [CI], .49-1.16). With respect to morbidity, antibiotic prophylaxis did not protect against infected necrosis (RR, .79; 95% CI, .56-1.11) or surgical intervention (RR, .88; 95% CI, .65-1.20). There was, however, an apparent benefit in regards to nonpancreatic infections (RR, .60; 95% CI, .44-.82), with a RR reduction of 40% (95% CI, 18%-56%), absolute risk reduction of 15% (95% CI, 6%-23%), and number needed to treat of 7 (95% CI, 4-17).

Conclusions

Antibiotic prophylaxis of SAP does not reduce mortality or protect against infected necrosis, or frequency of surgical intervention.     

儿童眼移植物抗宿主病诊治进展

眼移植物抗宿主病是造血干细胞移植术后的常见并发症之一,主要临床表现为干眼,病情进展可出现角膜溃疡穿孔、眼表衰竭等严重并发症,影响患者视力和生活质量。目前,国际上已有较多关于成人眼移植物抗宿主病的研究及临床规范,但关于儿童眼移植物抗宿主病的研究尚未受到足够关注,缺乏相关的基础数据和诊断标准。儿童对眼部症状表述能力有限、临床检查欠合作,眼科医师对该病认识不足,导致该病易被漏诊误诊。因此,本文从发病机制、发生率、危险因素、临床表现、诊断和治疗对儿童眼移植物抗宿主病的研究进展进行综述,以期为未来加强儿童此疾病的临床研究、拓展基础研究等提供思路。     

Improved outcomes using G‐CSF‐mobilized blood and bone marrow grafts as the source of stem cells compared with G‐PB after HLA‐identical sibling transplantation in patients with acute leukemia

This retrospective study compared the transplantation outcomes of 98 consecutive patients with acute leukemia. Allogeneic hematopoietic stem cell transplantation was performed using G‐CSF‐mobilized bone marrow and blood (G‐BM&PB) or G‐CSF‐mobilized peripheral blood (G‐PB) from HLA‐identical sibling donors. The G‐BM&PB and G‐PB groups displayed significantly different neutrophil recovery rates (medians of 15 vs. 14 d, respectively; p = 0.009) but similar platelet recovery rates. The cumulative incidences of grades II–IV acute graft‐versus‐host disease (aGVHD) in the G‐BM&PB and G‐PB cohorts were similar (16.2 ± 4.7% vs. 21.8 ± 7.4%, respectively; p = 0.676), but the incidences of grades III‐IV aGVHD were significantly different (5.5 ± 3.1% vs. 18.9 ± 7.1%, respectively; p = 0.042). The G‐BM&PB and G‐PB cohorts displayed similar cumulative incidences of chronic GVHD (cGVHD, 49.1 ± 5.7% vs. 42.7 ± 6.8%, respectively; p = 0.465), one‐yr cumulative incidences of treatment‐related mortality (16.5 ± 3.5% vs. 24.4 ± 4.1%, respectively; p = 0.220), and five‐yr cumulative incidences of relapse (13.9 ± 4.8% vs. 26.8 ± 7.2%, respectively; p = 0.113). The five‐yr probability of leukemia‐free survival (LFS) was significantly higher in the G‐BM&PB group than in the G‐PB group (77.8 ± 5.2% vs. 57.6 ± 8.6%, respectively; p = 0.023). Multivariate analysis identified G‐PB as an independent risk factor for grades III‐IV aGVHD and LFS. Our results suggest that HLA‐identical transplantation with G‐BM&PB results in superior clinical outcomes compared with G‐PB for patients with acute leukemia.     

Taking the challenge: A protocolized approach to optimize Pneumocystis pneumonia prophylaxis in renal transplant recipients

While trimethoprim‐sulfamethoxazole is considered first‐line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim‐sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty‐two patients (35%) had 48 trimethoprim‐sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non‐immune‐mediated and 17% were immune‐mediated. Significantly more patients underwent trimethoprim‐sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; P = .0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self‐limiting with only 1 recurrence of an immune‐mediated reaction. After protocol implementation, aerosolized pentamidine‐associated costs were reduced. The introduction of a standard approach to trimethoprim‐sulfamethoxazole rechallenge in the context of both prior immune and non‐immune‐mediated reactions was safe and successful in improving the uptake of first‐line Pneumocystis pneumonia prophylaxis in renal transplant recipients.     

蛋白酶激活受体-1,2在小鼠急性移植物抗宿主病模型中的表达

目的 研究蛋白酶激活受体-1,2(PAR-1,2)在小鼠急性移植物抗宿主病(aGVHD)模型中的表达.方法 建立小鼠异基因造血干细胞移植(allo-HSCT)后aGVHD模型,并用同基因HSCT小鼠作为对照.观察小鼠aGVHD表现;实时荧光定量聚合酶链反应、蛋白印迹和免疫组织化学法检测移植小鼠各种组织中PAR-1,2在基因和蛋白水平的表达.结果 allo-HSCT小鼠在移植后18～28 d出现了典型的aGVHD临床和病理表现.PAR-1基因在allo-HSCT组小鼠的皮肤、肝脏和小肠组织中的相对表达量较对照组显著增高(皮肤:0.039±0.013和0.008±0.002,P<0.01;肝脏:0.165±0.084和0.017±0.006,P<0.01;小肠:0.215±0.109和0.016±0.009,P<0.01);PAR-2基因在allo-HSCT组小鼠的肝脏和小肠组织中表达较对照组增高(肝脏:0.010±0.003和0.003±0.002,P<0.01;小肠:0.006±0.002和0.003±0.002,P<0.05);PAR-1,2基因在其余器官组织中的表达与对照组比较,差异无统计学意义.PAR-1,2在蛋白水平的表达与基因表达的检测结果一致.免疫组织化学染色显示PAR-1,2主要在aGvHD靶器官的上皮细胞和内皮细胞中表达增强.结论 PAR-1,2表达增高很有可能参与异基因造血干细胞移植后aGVHD的病理生理过程.     

异基因造血干细胞移植受者外周血中可溶性HLA-G与急性GVHD的相关性

目的 探讨异基因造血干细胞移植(allo-HSCT)受者外周血中可溶性HLA-G(sHLA-G)的水平与急性移植物抗宿主病(aGVHD)间的相关性以及与CD4+CD25~(hlgh)调节性T淋巴细胞(Treg)水平的相关性.方法 选择27例allo-HSCT受者,将其中13例术后发生aGVHD者作为aGVHD组,14例未发生aGVHD者作为对照组.在移植预处理前、移植后第2、4、8、14周时,分别抽取两组受者清晨空腹肘静脉血2～4 ml,采用酶联免疫吸附试验双抗夹心法定量检测sHLA-G,采用流式细胞术检测CD4+CD25+Treg.动态监测术后第2和14周受者sHLA-G水平的变化;动态监测和分析术后第8和14周两组受者间sHLA-G的差异.观察sHLA-G与发生aGVHD的相关性;检测术后第14周两组受者CD4+CD25+Treg的数量,观察sHLA-G水平与CD4+CD25+Treg的相关性.结果 预处理前,对照组和aGVHD组受者sHLA-G的水平分别为(75.4±13.1)/μg/L和(47.0±14.1)btg/L,两组间差异有统计学意义(P<0.05).术后第8周和第14周,对照组受者sHLA-G的水平明显高于相应时间点aGVHD组受者,两组间差异均有统计学意义(P<0.01).对照组受者术后第14周的sHLA-G水平与第2周相比,增长了1.2～3.4倍,两时间点的差异有统计学意义(P<0.05).术后第14周,通过Spearman等级相关检验显示受者sHLA_G水平与CD4+CD25+Treg比例具有统计学上的相关性(相关系数r=0.810,P<0.05),结论 allo-HSCT后受者体内sHIA-G对aGVHD的发生起负性调节作用;sHLA-G的水平与外周血CD4+CD25~(hlgh) T淋巴细胞的比例旱正相关,二者之间可能存在相互诱导和调节的信号途径,在诱导和维持移植免疫耐受中起着重要的协同作用.