异基因造血干细胞移植治疗复发或难治性霍奇金淋巴瘤患者：HDR-ALLO 研究结果——一项由西班牙淋巴瘤研究组/骨髓移植组（GEL/TAMO）和欧洲血液与骨髓移植学会淋巴瘤工作组开展的前瞻性临床试验。

Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

机构信息

Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

出版信息

Haematologica. 2012 Feb;97(2):310-7. doi: 10.3324/haematol.2011.045757. Epub 2011 Oct 11.

DOI:10.3324/haematol.2011.045757

PMID:21993674

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3269494/

Abstract

BACKGROUND

Although Hodgkin's lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting.

DESIGN AND METHODS

In this phase II study 92 patients with relapsed Hodgkin's lymphoma and an HLA-identical sibling, a matched unrelated donor or a one antigen mismatched, unrelated donor were treated with salvage chemotherapy followed by reduced intensity allogeneic transplantation. Fourteen patients showed refractory disease and died from progressive lymphoma with a median overall survival after trial entry of 10 months (range, 6-17). Seventy-eight patients proceeded to allograft (unrelated donors, n=23). Fifty were allografted in complete or partial remission and 28 in stable disease. Fludarabine (150 mg/m(2) iv) and melphalan (140 mg/m(2) iv) were used as the conditioning regimen. Anti-thymocyte globulin was additionally used as graft-versus-host-disease prophylaxis for recipients of grafts from unrelated donors.

RESULTS

The non-relapse mortality rate was 8% at 100 days and 15% at 1 year. Relapse was the major cause of failure. The progression-free survival rate was 47% at 1 year and 18% at 4 years from trial entry. For the allografted population, the progression-free survival rate was 48% at 1 year and 24% at 4 years. Chronic graft-versus-host disease was associated with a lower incidence of relapse. Patients allografted in complete remission had a significantly better outcome. The overall survival rate was 71% at 1 year and 43% at 4 years.

CONCLUSIONS

Allogeneic stem cell transplantation can result in long-term progression-free survival in heavily pre-treated patients with Hodgkin's lymphoma. The reduced intensity conditioning approach significantly reduced non-relapse mortality; the high relapse rate represents the major remaining challenge in this setting. The HDR-Allo trial was registered in the European Clinical Trials Database (EUDRACT, https://eudract.ema.europa.eu/) with number 02-0036.

摘要

背景

尽管霍奇金淋巴瘤（Hodgkin's lymphoma）采用现代化疗方案可实现高度治愈，但部分患者在一线化疗后、甚至在接受高剂量治疗和自体干细胞移植后仍会出现原发性耐药或复发。我们研究了异体干细胞移植在此情况下的潜在作用。

设计和方法

在这项 II 期研究中，92 例复发霍奇金淋巴瘤患者与 HLA 完全相合的同胞、匹配的无关供者或单抗原不合的无关供者接受挽救性化疗，随后接受强度降低的异体移植。14 例患者出现难治性疾病，死于进行性淋巴瘤，中位总生存期为入组后 10 个月（范围：6-17 个月）。78 例患者接受了同种异体移植（无关供者，n=23）。50 例患者在完全或部分缓解时接受移植，28 例在疾病稳定时接受移植。氟达拉滨（150mg/m2 iv）和马法兰（140mg/m2 iv）作为预处理方案。对于接受无关供者移植物的患者，加用抗胸腺细胞球蛋白预防移植物抗宿主病。

结果

100 天时的非复发死亡率为 8%，1 年时为 15%。复发是失败的主要原因。从入组开始，1 年时的无进展生存率为 47%，4 年时为 18%。对于接受同种异体移植的患者，1 年时的无进展生存率为 48%，4 年时为 24%。慢性移植物抗宿主病与较低的复发率相关。完全缓解时接受移植的患者具有显著更好的结局。1 年时的总生存率为 71%，4 年时为 43%。

结论

异体干细胞移植可使经大量预处理的霍奇金淋巴瘤患者获得长期无进展生存。强度降低的预处理方案显著降低了非复发死亡率；高复发率是这一情况下的主要遗留挑战。HDR-Allo 试验在欧洲临床试验数据库（EUDRACT，https://eudract.ema.europa.eu/）中注册，编号为 02-0036。