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抗淋巴细胞球蛋白预防慢性移植物抗宿主病。

Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease.

机构信息

From the University Medical Center Hamburg-Eppendorf, Hamburg (N.K., C.W., M.H., F.A.), University Hospital Freiburg, Freiburg (J.F.), University Hospital Tübingen, Tübingen (W.B.), and Psy Consult, Frankfurt (A.V.) - all in Germany; Hospital Clinico Universitario, Valencia (C. Solano), Hospital Ramon y Cajal (J.P.O.) and Hospital Universitario Puerta de Hierro Majadahonda (R.D.), Madrid, Servicio de Hematología, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, (C.F.), Hospital de la Santa Creu i Sant Pau, Barcelona (J.S.), and Hospital Virgen de las Nieves, Granada (M.J.) - all in Spain; S. Orsola-Malpighi University Hospital, University of Bologna, Bologna (G.B., F. Bonifazi), Hematology, DISM, University Udine, Udine (F.P.), Azienda Ospedaliera SS Antonio e Biagio e C. Arrigo, Alessandria (M. Pini), Università Federico II di Napoli, Naples (C. Selleri, A.R.), A.O. Bianchi-Melacrino-Morelli, Reggio Calabria (G. Messina), Ospedale Casa Sollievo della Sofferenza IRCCCS, San Giovanni Rotondo (A.M.C.), Azienda Ospedaliera San Carlo, Potenza (M.C.), Azienda Ospedaliera Careggi, Florence (S.G.), Ospedale Santa Croce, e Carle, Cuneo (N.M.), University of Brescia, Department of Clinical and Experimental Sciences, Brescia (D.R.), University of Pisa, Department of Clinical and Experimental Medicine, Pisa (M. Petrini), Programma di Trapianto Emopoietico Metropolitano, Azienda Policlinico-Vittorio Emanuele, Catania (G. Milone), Policlinico G.B. Rossi, Verona (F. Benedetti), Azienda Ospedaliera, Universitaria Ospedale, Bari (D.P.), Ospedale San Gerardo, Monza (E.T.), Policlinico Modena, Modena (F.N.), and Università di Salerno, Salerno (C. Selleri) - all in Italy; Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel (A.N.); and Helsinki University Hospital, Helsinki (T.R.).

出版信息

N Engl J Med. 2016 Jan 7;374(1):43-53. doi: 10.1056/NEJMoa1506002.

DOI:10.1056/NEJMoa1506002

PMID:26735993

Abstract

BACKGROUND

Chronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling.

METHODS

We conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of a conditioning regimen. A total of 168 patients were enrolled at 27 centers. Patients were randomly assigned in a 1:1 ratio to receive ATG or not receive ATG, with stratification according to center and risk of disease.

RESULTS

After a median follow-up of 24 months, the cumulative incidence of chronic GVHD was 32.2% (95% confidence interval [CI], 22.1 to 46.7) in the ATG group and 68.7% (95% CI, 58.4 to 80.7) in the non-ATG group (P<0.001). The rate of 2-year relapse-free survival was similar in the ATG group and the non-ATG group (59.4% [95% CI, 47.8 to 69.2] and 64.6% [95% CI, 50.9 to 75.3], respectively; P=0.21), as was the rate of overall survival (74.1% [95% CI, 62.7 to 82.5] and 77.9% [95% CI, 66.1 to 86.1], respectively; P=0.46). There were no significant between-group differences in the rates of relapse, infectious complications, acute GVHD, or adverse events. The rate of a composite end point of chronic GVHD-free and relapse-free survival at 2 years was significantly higher in the ATG group than in the non-ATG group (36.6% vs. 16.8%, P=0.005).

CONCLUSIONS

The inclusion of ATG resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. The survival rate was similar in the two groups, but the rate of a composite end point of chronic GVHD-free survival and relapse-free survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.).

摘要

背景

慢性移植物抗宿主病（GVHD）是异基因造血干细胞移植后导致患者后期发病和死亡的主要原因。我们假设，在接受 HLA 配型相同的同胞外周血造血干细胞移植的急性白血病患者中，在清髓性预处理方案中加入抗人 T 淋巴细胞免疫球蛋白（ATG），可显著降低慢性 GVHD 在移植后 2 年的发生率。

方法

我们开展了一项前瞻性、多中心、开放性、随机 3 期临床试验，评估了 ATG 作为预处理方案的一部分的效果。共 27 家中心的 168 例患者入组。患者按照 1:1 的比例随机分配接受 ATG 或不接受 ATG，分层因素为中心和疾病风险。

结果

中位随访 24 个月后，ATG 组慢性 GVHD 的累积发生率为 32.2%（95%置信区间[CI]，22.1%至 46.7%），而非 ATG 组为 68.7%（95%CI，58.4%至 80.7%）（P<0.001）。ATG 组和非 ATG 组的 2 年无复发生存率相似（分别为 59.4%[95%CI，47.8%至 69.2%]和 64.6%[95%CI，50.9%至 75.3%]；P=0.21），总生存率也相似（分别为 74.1%[95%CI，62.7%至 82.5%]和 77.9%[95%CI，66.1%至 86.1%]；P=0.46）。两组间复发率、感染性并发症、急性 GVHD 或不良事件发生率无显著差异。ATG 组 2 年时慢性 GVHD 无复发和无复发生存的复合终点发生率显著高于非 ATG 组（36.6% vs. 16.8%；P=0.005）。