A gut microbiota score predicting acute graft‐versus‐host disease following myeloablative allogeneic hematopoietic stem cell transplantation

Although studies have reported that intestinal microbiota are associated with acute graft‐versus‐host disease (aGVHD), they lacked a satisfactory method for predicting aGVHD. We collected stool and blood samples at day 15 posttransplant from 150 patients from two centers who underwent myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Stool microbiota were detected by 16S ribosomal RNA gene sequencing; inflammatory factors and T lymphocytes were detected by multiplex immunoassays and flow cytometry, respectively. A gut microbiota score (GMS) from a LASSO (least absolute shrinkage and selection operator) model was developed and validated to predict aGVHD. In the discovery cohort, the GMS could predict II‐IV aGVHD (area under the receiver operating characteristic [ROC] curve [AUC] = 0.904, P < .0001). Furthermore, the validation model was consistent with the discovery set (AUC = 0.887, P < .0001). Regulatory T/T‐helper 17 (Treg/Th17) cells ratio in the low GMS subgroup was higher compared with the high GMS (P = .012), and the validation set is consistent with the discovery set (P = .003). In addition, high cytokine levels were associated with high GMS. In conclusion, the GMS at neutrophil engraftment could predict aGVHD, and it was a potential and novel method. The GMS was associated with the inflammatory factor and Treg/Th17 balance.     

Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Thrombotic microangiopathy (TMA) has been described as severe complication after hematopoietic stem cell transplantation (HSCT). The principal aim of this study was to focus the incidence and the outcome of TMA in the era of more complex HSCTs. METHODS: We analyzed the role of some predicting factors for the incidence and the outcome of TMA after HSCT. We enrolled 539 consecutive patients (307 males, median age 31 years) undergoing HSCT from match or mismatch human leukocyte antigen family donor (314) or match/mismatch unrelated (195) and haploidentical donor (30) for malignant or nonmalignant diseases. TMA diagnosis was performed by homogeneous clinical and laboratory criteria. RESULTS: Sixty-four of 539 patients presented TMA (11,87%) and the five-year cumulative incidence of TMA was 14% (HR=0.13). Fifty nine of 64 patients were affected by malignant and 5/64 by non-malignant diseases. On multivariate analysis, TMA occurrence was influenced by graft versus host disease >grade II (P=0.0001), donor type (P=0.029), gender (P=0.0233), total body irradiation based conditioning regimen (P=0.0041). Three factors for TMA outcome proved to be statistically significant by multivariate analysis: age (P=0.009), donor type (P=0.0187) and TMA index (P=0.029). The TMA mortality rate was 50%. The outcome was influenced by defibrotide (P=0.02 in univariate analysis). CONCLUSIONS: The study underlines the possibility of finding out which patients are more prone to developing post-HSCT TMA, and identifies which risk factors are more frequently associated with a dismal outcome after TMA.     

Associations between acute GVHD-related biomarkers and endothelial cell activation after allogeneic hematopoietic stem cell transplantation

BackgroundHematopoietic stem cell transplantation (HSCT) can cause serious transplant-related complications such as graft-versus-host disease (GVHD). Acute GVHD (aGVHD) has been diagnosed by clinical manifestations, laboratory data and pathological effects until now, but recently the discovery of specific biomarkers such as suppression of tumorigenicity 2 (ST2), elafin and regenerating islet-derived 3α (REG3α) is challenging this approach.MethodsWe investigated the expression of aGVHD-related markers (regulated on activation normal T-cell expressed and secretes: RANTES, elafin, REG3α and ST2) and endothelial cell activation markers (soluble vascular cell adhesion molecule: sVCAM-1 and plasminogen activator inhibitor: PAI-1) in patients undergoing allogeneic HSCT. Additionally, we studied the effects of recombinant soluble thrombomodulin (rTM) on the expression of these markers. Our study cohort included 225 patients who underwent allogeneic HSCT at several institutions in Japan.ResultsRANTES, sVCAM-1, PAI-1, elafin, REG3α and ST2 exhibited significant increases in patients not receiving rTM after HSCT. When we examined patients with confirmed complications, the frequencies of aGVHD and VOD were significantly lower in the rTM-treated group. In addition, aGVHD-related biomarkers such as elafin, REG3α, and ST2 were elevated significantly in patients with aGVHD.ConclusionOur findings suggest that endothelial cell activation might be linked to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its effect on endothelial cells.     

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。     

ABO血型主要不合异基因造血干细胞移植后纯红细胞再生障碍的临床分析

目的探讨ABO血型主要不合者异基因造血干细胞移植（allo-HSCT）后并发纯红细胞再生障碍（PRCA）的危险因素、临床转归以及PRCA的治疗和预防。方法42例行allo-HSCT，其中供、受者AN）血型主要不合者33例，主次双向不合者9例，27例受者血型为O型。预处理后，13例行骨髓移植，25例行外周血干细胞移植，4例行脐血移植。6例移植前行供者型血浆置换。移植后采用环孢素A（CsA）及短程甲氨蝶呤（MTX）联用预防移植物抗宿主病（GVHD）。结果42例均获得供者细胞植入，11例移植后并发PRCA（26．2％），11例的血型均为O型，其供者9例为A型，2例为B型；移植前行供者型血浆置换的O型受者，移植后均未发生PRCA。并发PRCA的11例中，8例经红细胞输注后自然缓解，2例行供者型血浆置换，其凝集素滴度下降后缓解，1例予利妥昔单抗治疗后缓解。单因素分析表明，O型受者、A型供者以及A型供给O型者与PRCA的发生相关，多因素分析表明，A型供给0型者是发生PRCA的独立危险因素（RR为10．999，95％可信区间为1．975-61．258，P〈0．05）。结论A型供给O型者与PRCA的发生密切相关；移植前行供者型血浆置换可预防PRCA的发生；供者型血浆置换和利妥昔单抗可有效治疗PRCA。     

T helper 17 and regulatory T-cell profile and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in pediatric patients with beta-thalassemia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for hereditary hemoglobin disorders, such as beta-thalassemia; However, this procedure is not without constraints, mainly engendering complications such as acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), and susceptibility to infections. The clinical outcomes of allo-HSCT are highly dependant on the quality and quantity of T-cell subsets reconstitution. Following the allo-HSCT of six pediatric patients afflicted with beta-thalassemia, their mononuclear cells were isolated, and then cultured with a combination of phorbol myristate acetate (PMA)/ionomycin and Brefeldin A. The content of CD4 T-cell subsets, including T helper 17 (Th17) cells and regulatory T cells (Tregs), were determined by specific conjugated-monoclonal antibodies three and six months post-HSCT. An increased frequency of total CD4 T-cells, Tregs and Th17 cells was observed at day 90 and 180 after allo-HSCT, albeit the numbers were still lower than that of our healthy controls. In patients who developed cGvHD, a lower Th17/Treg ratio was observed, owing it to a decreased proportion of Th17 cells. In conclusion, creating balance between Th17 and Treg subsets may prevent acute and chronic GvHD in patients after allo-HSCT.     

供者NK细胞及其嵌合状态在异基因造血干细胞移植中的研究进展

目前,异基因造血干细胞移植(allo-HSCT)已广泛应用于造血系统疾病的治疗,但移植术后也存在一系列并发症。NK细胞的运用为改善allo-HSCT受者预后带来希望,供者来源NK细胞通过其细胞膜上的杀伤细胞免疫球蛋白样受体与其配体错配发挥同种异体反应,该过程具有保留移植物抗白血病和减少移植物抗宿主病双重效应。NK细胞是allo-HSCT后受者体内最早重建的免疫细胞群,因此移植后供、受者NK细胞嵌合状态评估对预测疾病预后及指导干预治疗具有重要意义。基于NK细胞嵌合状态的供者NK细胞输注免疫干预疗法可改善疾病预后,在血液系统疾病治疗中表现出良好的应用前景。本文就近年来供者NK细胞及其嵌合状态在allo-HSCT中的研究进展作一综述。     

高危急性髓系白血病异基因造血干细胞移植后复发的防治

急性髓系白血病（AML）是一组高度异质性的克隆性疾病,化学药物治疗和造血干细胞移植均为治疗AML的方法。对于高危AML患者而言,异基因造血干细胞移植为治疗该疾病的有效手段,但部分AML患者造血干细胞移植后仍可能面临疾病复发的问题,大多数复发患者再行化学药物治疗、二次移植等的效果不佳,是导致患者异基因造血干细胞移植后死亡的主要原因。因此,加强对异基因造血干细胞移植后AML患者的随访,并采取一些合适的手段预防移植后复发显得尤为重要。本文就高危AML患者异基因造血干细胞移植后复发的监测、药物治疗和细胞治疗进行综述,以期为改善高危AML患者异基因造血干细胞移植预后提供参考。     

Clinical features of late onset non-infectious pulmonary complications following pediatric allogeneic hematopoietic stem cell transplantation

Park M, Koh KN, Kim BE, Im HJ, Seo JJ. Clinical features of late onset non‐infectious pulmonary complications following pediatric allogeneic hematopoietic stem cell transplantation.
Clin Transplant 2011: 25: E168–E176. © 2010 John Wiley & Sons A/S. Abstract: Background: Late onset non‐infectious pulmonary complications (LONIPCs) are major causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We evaluated the incidence and the outcomes of LONIPCs in children who underwent allo‐HSCT. Methods: Data for 143 children who underwent allo‐HSCT at Asan Medical Center between April 2002 and April 2009 were reviewed, and the 127 who survived more than three months were enrolled. Results: Eleven (8.7%) developed LONIPCs at a median eight months (range 3–14 months) after allo‐HSCT, presenting with cough and dyspnea. Six had bronchiolitis obliterans and five had idiopathic pneumonia syndrome. FVC declined more significantly in LONIPC than in non‐LONIPC patients three months after HSCT. A significant risk factor for the development of LONIPCs was chronic graft‐versus‐host disease (GVHD) (p = 0.002). At a median follow‐up of 36 months, the three‐yr overall survival rate in LONIPC patients was significantly lower than that of non‐LONIPC patients (37.4% vs. 72.7%, p = 0.02). The major cause of death was respiratory failure. Conclusions: Along with chronic GVHD, deterioration of pulmonary function at three months after HSCT may help in the early identification of patients at risk of subsequent LONIPCs. Considering the poor prognosis of LONIPC, strategies should be aimed at their prevention.     

异基因造血干细胞移植后并发出血性膀胱炎的高危因素和防治措施

目的 评估改良的水化碱化方案对预防和治疗非亲缘异基因造血干细胞移植(URD-HSCT)后出血性膀胱炎(HC)的效果及安全性,探讨URD-HSCT后并发HC的危险因素.方法 151例血液系统恶性疾病患者接受了URD-HSCT,所有患者移植前均接受白消安+环磷酰胺(BuCy2)方案预处理.在使用环磷酰胺(Cy)过程中,所有患者均接受改良的水化碱化输液方案,分别在静脉滴注Cy后0、3、6、9、12 h分5次静脉注射美司钠,总量为Cy总量的120%～160%;于开始使用Cy时至结束后24 h(共计72 h)经中心静脉持续输液,输液量5000 ml·m-2·d-1,匀速输注,每500 ml液体中加入50 g/L碳酸氢钠20 ml,间断应用利尿剂,保持液体出入量平衡;每小时测尿pH值,保持尿pH值＞7.5.结果 URD-HSCT后共有26例患者发生HC,发生率为17.2%(26/151),中位发病时间为40d(8～89 d),无患者发生早发性HC.移植后26例HC患者再次接受改良的水化碱化尿液治疗,部分患者接受膀胱持续冲洗,所有患者均治愈,无患者因HC而死亡.经统计分析表明,以下因素与HC的发病明显相关:男性患者,相关系数(OR)值=3.093,95%可信区间(CI)为1.145～8.353,P＜0.05;急性GVHD,OR值=18.044,95%CI为3.952～82.392,P＜0.01;≥30岁,OR值=6.077,95%CI为1.585～23.299,P＜0.01.结论 改良的水化碱化方案是预防和治疗URD-HSCT后HC的安全有效的措施,尤其是由Cy预处理引起的早发性HC;男性患者、年龄≥30岁以及移植后并发急性GVHD是引起HC的危险因素.

Abstract：

Objective To investigate the efficacy and safety of the optimal alkalized hydration solution for hemorrhagic cystitis (HC) following unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT), and the risk factors and prophylaxis measures about HC.Methods The clinical data of 151 HC patients who underwent URD-HSCT were retrospectively analyzed. All patients were given busulfan/cyclophosphamide (BuCy)-based conditioning regimen.During Cy therapy, all patients were given the optimal alkalized hydration solution to prevent HC.MESNA was given intravenously after administration of Cy at 0, 3, 6, 9, 12 h, and its total dose was administration of Cy to 24 h under the ECG monitoring. Each 500 ml liquid contained 50 g/L sodium bicarbonate 20 ml. Urinary pH value was monitored every one hour (keeping urine pH＞7. 5). Results None of early onset HC occurred. Twenty-six of 151 (17. 2 %) patients developed late onset HC, and the median onset time was 40 (8～89) days after transplantation. During the therapy, no symptoms of the circulatory system, no congestive heart failure and no acid-base electrolyte imbalance occurred. All HC patients after re-hydration, diuretic, and (or) continuous bladder irrigation and other indwelling catheter after treatment, were cured. The statistical analysis showed that the following factors were significantly associated with HC: male (OR = 3. 093, 95 % CI, 1. 145～8.353, P＜0. 05), acute graft versus host disease (aGVHD) (OR= 18. 044, 95 % CI, 3. 952～～82. 392, P＜0. 01), and ≥30-yearold (OR = 6. 077, 95 0% CI, 1. 585～23. 299, P＜0. 01). Conclusion The optimal alkalized hydration solution is safe and effective to prevent early onset HC following URD-HSCT in combination with BuCy regimen. Male, aGVHD and ≥30-year-old were the risk factors for HC.     

异基因造血干细胞移植后动态监测调节性T淋巴细胞的临床意义

目的探讨监测调节性T淋巴细胞（Treg）的动态变化在异基因造血干细胞移植（allo-HSCT）中的临床意义。方法选择45例allo-HSCT患者，其中31例采用短程甲氨蝶呤（MTX）联合环孢素A（CsA）预防移植物抗宿主病（GVHD），另14例加用霉酚酸酯（MMF）和达利珠单抗（抗CD25单克隆抗体）强化GVHD的预防。采用流式细胞术动态监测allo-HScT患者移植预处理前、移植后2、4、8、12周时及发生急性移植物抗宿主病（aGVHD）时外周血Treg的水平；分析Treg水平的变化与aGVHD发生的相互关系。结果45例患者中，发生Ⅱ～Ⅳ度aGVHD10例。移植后8和12周时，未使用达利珠单抗组中发生Ⅱ～Ⅳ度aGVHD较发生0～I度aGVHD的患者外周血Treg水平显著降低，差异有统计学意义（P〈0．05）；患者发生Ⅱ～Ⅳ度aGVHD后，外周血Treg水平较发生前显著降低，差异有统计学意义（P〈0．05）。使用达利珠单抗组的患者外周血Treg水平在各时间点均明显降低，各时点间比较，差异均无统计学意义。结论Treg的动态变化与aGVHD的关系密切，可作为临床监测aGVHD发生的重要指标之一；达利珠单抗的应用显著降低了外周血Treg的水平，其对aGVHD的预防作用有待今后深入研究。     

Role of plasmacytoid dendritic cells in immunity and tolerance after allogeneic hematopoietic stem cell transplantation

Dendritic cells (DC) may play an important role in the pathogenesis of alloimmune reactions, such as graft-vs.-host disease after allogeneic hematopoietic stem cell transplantation (HSCT). In humans, two types of DC-myeloid DC (mDC) and plasmacytoid DC (pDC) have been characterized and have distinct origins and functions. The data obtained from studies in vitro suggest that pDC are involved in the regulation of immunity, including the induction and maintenance of tolerance, as well as in the defence against viruses. The authors will review all the evidence currently available from reports exploring the role of pDC in clinical allogeneic HSCT.     

重型再生障碍性贫血的治疗与造血干细胞移植

重型再生障碍性贫血（SAA）是由多种病因导致的重度骨髓造血功能衰竭综合征,临床以严重的贫血、感染、出血为主要特征。SAA发病机制复杂,至今尚未完全明了。SAA起病急,病情重,病情进展快,目前随着对SAA的深入研究以及诊疗水平的提高,对于其治疗策略也发生了改变。从经典的免疫抑制治疗,即主要以抗胸腺细胞球蛋白和环孢素为基础的治疗方案,到血小板生成素受体激动剂的应用及以异基因造血干细胞移植等为基础的联合治疗方案,均不同程度促进SAA患者的造血功能重建,极大改善其生存及预后,成为当下SAA治疗的研究热点。本文结合国内外文献对SAA治疗的新进展进行综述。     

骨髓或外周血中CD4+CD25+Foxp3+调节性T淋巴细胞与aGVHD的关系

目的 研究患者异基因造血干细胞移植(allo-HSCT)前后骨髓或外周血单个核细胞中CD4+CD25+Foxp3+调节性T淋巴细胞(以下简称CD4+CD25+Foxp3+T细胞)的比率、Foxp3 mRNA和Foxp3蛋白的表达与急性移植物抗宿主病(aGVHD)的关系.方法 选择37例行HIA相合异基因造血干细胞移植(allo-HSCT))的患者作为研究对象.采用流式细胞术检测患者allo-HSCT前7天(-7 d)、移植当天(0 d)、移植后30天(+30d)、+60 d和+90 d时骨髓或外周血单个核细胞中CD4+CD25+Foxp3+T细胞所占的比率;定量聚合酶链反应(PCR)检测Foxp3 mRNA相对表达量;蛋白印迹(Western blot)法检测Foxp3的蛋白表达水平.结果 37例患者存移植后100 d内发生aGVHD 13例(aGVHD组),未发生aGVHD 24例(无aGVHD组).CD4+CD25+Foxp3+T细胞的比率在0 d时最低,与-7、+30、+60、+90d时比较.差异均有统计学意义(P<0.01);与aGVHD组比较,无aGVHD组患者的CD4+CD25+Foxp3+T细胞的比率明显升高,差异有统计学意义(P<0.01).aGVHD组患者移植后Foxp3的表达水平逐渐升高,但明显低于无aGVHD组,尤其在+60和+90 d时的差异有统计学意义(P<0.01).Western blot法检测结果 表明,aGVHD组受者的Foxp3蛋白表达也明显低于无aGVHD组.结论 CD4+CD25+Foxp3+T细胞对防止发生aGVHD具有重要作用,监测患者骨髓或外周血中CD4+CD25+Foxp3+T细胞的比率可以预测aGVHD的发生.     

T cell mixed chimerism is significantly correlated to a decreased risk of acute graft-versus-host disease after allogeneic stem cell transplantation

BACKGROUND: It has been debated whether mixed chimerism (MC) is correlated to a decreased incidence of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). METHODS: Between September 1996 and April 1999 we analyzed 102 patients for MC in the T-cell fraction post allogeneic SCT, using PCR amplification of variable numbers of tandem repeat (VNTR) loci. All samples, taken regularly post SCT, were cell separated using anti-CD3 immunomagnetic beads. RESULTS: T-cell mixed chimerism was detected in 58 out of 102 patients (57%). Patient characteristics were comparable in the T-cell MC- and donor chimeric-group (DC). The median follow-up time for the MC group was 714 days (range 58 - 1248) as compared to 427 days (range 45 - 1042) for the DC group. Overall probability of acute GVHD grades II-IV was significantly higher in the DC group as compared to the MC group (52% vs. 5%, P<0.001). In multivariate analysis T-cell DC proved to be the most significant risk factor for acute GVHD grades II-IV. The cumulative incidence of relapse, among patients with malignant disease, did not show any statistical difference between the T-cell MC patients and the DC-group. There was a tendency for better overall survival in the T-cell MC group compared to the DC group (2 yrs; 73% vs. 54%, P=0.06). Among DC patients, 14/20 (70%) deaths were due to GVHD versus none in the MC-group(P<0.001). CONCLUSION: T-cell mixed chimerism was significantly correlated to a decreased risk of moderate to severe acute GVHD and death by GVHD.     

The significance of cytomegalovirus viremia at day 100 or more following allogeneic hematopoietic stem cell transplantation

We conducted a single‐center retrospective review of patients who had received allogeneic hematopoietic stem cell transplantation (HSCT) between January 2003 and December 2007, to assess the incidence and risk factors for late CMV infection and evaluate its effects on outcomes. Twenty of 49 HSCT recipients (41%) developed CMV infection at day ≥100 after transplant. Univariable analysis showed that having a matched unrelated donor, having early CMV infection, having a diagnosis of lymphoma, and receipt of antithymocyte globulin were risks for developing late CMV. On multivariable analysis, the occurrence of CMV prior to day 100 and lymphoma conferred a significant risk for late CMV infection. Of the 20 patients with late CMV infection, two patients manifested CMV disease (10%). Despite the relatively low incidence of CMV disease, patients with late CMV infection had a 4.8‐fold increased risk of death compared to patients without late CMV. Identifying patients at increased risk for developing late CMV infection may be important for prompting more intensive monitoring of infection late after HSCT, particularly because this manifestation of CMV is associated with poorer outcomes.     

A case–control study of bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplantation

Bronchiolitis obliterans syndrome (BOS) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the pathogenesis and risks for the development of BOS have remained unclear. Therefore, a case–control study was conducted to investigate the risk factors for the development of BOS, which included the largest number of BOS cases; 196 patients with BOS were identified and compared with 1960 control recipients. The following were identified as significantly higher risk factors for the development of BOS: female recipients (OR 1.47, P = 0.019), ABO‐mismatch HSCT (minor mismatch, OR 1.67, P = 0.015; major mismatch, OR 1.73, P = 0.012; bidirectional mismatch, OR 1.96, P = 0.018), busulfan+cyclophosphamide‐based myeloablative conditioning (OR 1.74, P = 0.016), and acute graft‐versus‐host disease (GVHD) involving the skin (OR 1.55, P = 0.011). On the other hand, the risk for the development of BOS was significantly lower in patients receiving cord blood transplantation (OR 0.26, P = 0.0011). With respect to other target organs of chronic GVHD, ocular involvement was significantly associated with BOS (OR 2.53, P < 0.001). Prospective studies are required to elucidate the risk factors for the development of BOS, and future investigations should focus on finding a prophylactic approach against BOS based on these findings.     

Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation

BACKGROUND: In the present investigation, we determined whether donor epithelial lung cells might be detected after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Lung-tissue specimens were obtained at autopsy from four female patients, two with male donors, after nonmyeloablative HSCT. Immunohistochemical staining for cytokeratin was used to identify lung epithelial cells. The tissue sections were analyzed for the presence of donor-derived lung epithelial cells with the use of fluorescence in situ hybridization of XY-positive cells. RESULTS: All patients showed almost complete donor chimerism in all cell lineages after HSCT with polymerase chain reaction of minisatellites. In the two positive controls, between 2% and 6% Y-chromosome-positive epithelial lung cells were detected in each section. Surfactant-positive male epithelial cells were also detected, indicating engraftment of type II pneumocytes. In the two negative controls, no Y-chromosome-positive cells were detected. CONCLUSION: Circulating donor stem cells may differentiate into lung epithelial cells after allogeneic HSCT.