Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley St, London WC1E 6BT United Kingdom.
J Clin Oncol. 2011 Mar 10;29(8):971-8. doi: 10.1200/JCO.2010.32.1711. Epub 2011 Jan 31.
Reduced-intensity conditioning has minimized nonrelapse-related mortality rates after allogeneic transplantation in patients with Hodgkin's lymphoma, and relapse has now become the major cause for treatment failure. We aimed to assess the impact of donor lymphocyte infusions (DLIs) on relapse incidence when administered for mixed chimerism and their utility as salvage therapy when given for relapse.
This study reports the outcomes of 76 consecutive patients with multiply relapsed or refractory Hodgkin's lymphoma who underwent allogeneic transplantation that incorporated in vivo T-cell depletion. Forty-two patients had related donors and 34 had unrelated donors. DLIs were administered in a dose-escalating fashion to 22 patients for mixed chimerism (median time of first dose, 9 months post-transplantation) and to 24 patients for relapse.
Three-year donor lymphocyte-related mortality was 7%, relating mainly to the induction of graft-versus-host disease. Nineteen (86%) of 22 patients receiving donor lymphocytes for mixed chimerism converted to full donor status. Four-year relapse incidence was 5% in these 22 patients compared with 43% in patients who remained relapse free but full donor chimeras at 9 months post-transplantation (P = .0071). Nineteen (79%) of 24 patients receiving donor lymphocytes for relapse responded (14 complete responses, five partial responses). Four-year overall survival from relapse was 59% in recipients of donor lymphocytes, contributing to a 4-year overall survival from transplantation of 64% and a 4-year current progression-free survival of 59% in all 76 patients.
These data demonstrate the potential for allogeneic immunotherapy with donor lymphocytes both to reduce relapse risk and to induce durable antitumor responses in patients with Hodgkin's lymphoma after hematopoietic stem-cell transplantation that incorporates in vivo T-cell depletion.
在霍奇金淋巴瘤患者接受异基因移植后，减强度预处理方案降低了非复发相关死亡率，而复发现在已成为治疗失败的主要原因。我们旨在评估供者淋巴细胞输注（DLI）在混合嵌合体时对复发发生率的影响，以及在复发时作为挽救治疗的效用。
本研究报告了 76 例接受包含体内 T 细胞耗竭的异基因移植的复发性或难治性霍奇金淋巴瘤患者的结果。42 例患者有亲缘供者，34 例患者有无亲缘供者。22 例患者因混合嵌合体而接受递增剂量的 DLI（移植后第 9 个月首次剂量中位数），24 例患者因复发而接受 DLI。
3 年供者淋巴细胞相关死亡率为 7%，主要与移植物抗宿主病的诱导有关。22 例接受 DLI 治疗混合嵌合体的患者中，有 19 例（86%）转为完全供者状态。在这 22 例患者中，4 年复发率为 5%，而在移植后 9 个月仍未复发但完全供者嵌合体的患者中，复发率为 43%（P =.0071）。24 例因复发而接受 DLI 的患者中，19 例（79%）有反应（14 例完全缓解，5 例部分缓解）。接受供者淋巴细胞治疗的患者 4 年总生存率为 59%，这使得 76 例患者的 4 年总生存率为 64%，4 年无进展生存率为 59%。
这些数据表明，在包含体内 T 细胞耗竭的造血干细胞移植后，异基因免疫疗法具有用供者淋巴细胞降低霍奇金淋巴瘤患者复发风险并诱导持久抗肿瘤反应的潜力。
