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人类白细胞抗原(HLA)全相合同胞造血干细胞移植中移植前宿主胸腺功能的预后价值

Prognostic value of pretransplantation host thymic function in HLA-identical sibling hematopoietic stem cell transplantation.

作者信息

Clave Emmanuel, Rocha Vanderson, Talvensaari Kimmo, Busson Marc, Douay Corinne, Appert Marie-Lorraine, Rabian Claire, Carmagnat Maryvonnick, Garnier Federico, Filion Alain, Socié Gérard, Gluckman Eliane, Charron Dominique, Toubert Antoine

机构信息

Laboratoire d'Immunologie et d'Histocompatibilité Assistance Publique-Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM) U396, Hôpital Saint-Louis, Paris, CEDEX 10, France.

出版信息

Blood. 2005 Mar 15;105(6):2608-13. doi: 10.1182/blood-2004-04-1667. Epub 2004 Nov 16.

Abstract

Thymic function is critical for immune reconstitution after hematopoietic stem cell transplantation (HSCT). We evaluated recipient thymic function before HSCT by quantifying T-cell receptor excision circles (TRECs) in pretransplantation peripheral blood lymphocytes from 102 patients who received HSCs from an HLA-identical sibling for malignant (n = 87) or nonmalignant diseases (n = 15). Median TREC value before transplantation was 257 TRECs per 150,000 CD3+ cells (range, 0-42,746). We assessed 172 TRECs per 150,000 CD3+ cells as the most discriminating TREC value for survival in a first cohort of patients (n = 62). This cut-off was validated in a second independent prospective group of 40 patients. In the 102 patients, a TREC value greater than or equal to 172 was associated with a better survival (P < .000 01), a decreased incidence of grade II-IV acute graft-versus-host disease (GVHD; P = .017), chronic GVHD (P = .023), and bacterial (P = .003) and cytomegalovirus (CMV) infection (P = .024). In a multivariate analysis, low pretransplantation TREC values were associated with a higher incidence of CMV infection (hazard ratio [HR] = 2.0, P = .06) and severe bacterial infections (HR = 2.8, P = .036). Finally, high TREC values (HR = 6.6, P = .002) and ABO compatibility (HR = 2.7, P = .02) were associated with a better survival. Therefore, recipient host thymic function assessment could be helpful in predicting HSCT outcome and identifying patients who require a close immunologic monitoring.

摘要

胸腺功能对于造血干细胞移植(HSCT)后的免疫重建至关重要。我们通过对102例接受来自 HLA 相同同胞的造血干细胞移植治疗恶性疾病(n = 87)或非恶性疾病(n = 15)患者的移植前外周血淋巴细胞中的 T 细胞受体切除环(TRECs)进行定量,评估了 HSCT 前受体的胸腺功能。移植前 TREC 的中位数为每150,000个 CD3 + 细胞中有257个 TREC(范围为0 - 42,746)。我们将每150,000个 CD3 + 细胞中有172个 TREC 评估为首批患者队列(n = 62)生存的最具区分性的 TREC 值。该临界值在第二个独立的40例患者前瞻性组中得到验证。在这102例患者中,TREC 值大于或等于172与更好的生存率相关(P <.000 01),II - IV 级急性移植物抗宿主病(GVHD)的发生率降低(P =.017),慢性 GVHD(P =.023)以及细菌感染(P =.003)和巨细胞病毒(CMV)感染(P =.024)。在多变量分析中,移植前 TREC 值低与 CMV 感染发生率较高(风险比[HR] = 2.0,P =.06)和严重细菌感染(HR = 2.8,P =.036)相关。最后,高 TREC 值(HR = 6.6,P =.002)和 ABO 血型相容性(HR = 2.7,P =.02)与更好的生存率相关。因此,受体宿主胸腺功能评估可能有助于预测 HSCT 结果并识别需要密切免疫监测的患者。

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