Lee C-K, de Magalhaes-Silverman M, Hohl R J, Hayashi M, Buatti J, Wen B C, Schlueter A, Strauss R G, Gingrich R D
Department of Internal Medicine, Division of Hematology, Oncology, Blood and Marrow Transplantation, University of Iowa, College of Medicine, Iowa City, IA, USA.
Bone Marrow Transplant. 2002 Apr;29(7):615-20. doi: 10.1038/sj.bmt.1703426.
Fifty-two patients with refractory lymphoma were prospectively treated with prophylactic T lymphocyte infusion after T cell-depleted allogeneic bone marrow transplantation, to induce graft-versus-lymphoma effect. Thirty-three patients had related donors; 19 had unrelated donors. After transplantation with marrow that had 0.8 +/- 0.4 x 10(5)CD3(+) cells/kg, T cells up to 1.75 x 10(6) CD3(+) cells/kg were given over 3 months provided > or = grade II acute graft-versus-host disease (GVHD) was not seen. The cumulative incidence of grades II-IV acute GVHD was 69%. Twenty of 32 evaluable patients (63%) developed chronic GVHD. Ten patients (19%) died of GVHD. The Kaplan-Meier 5-year overall survival of all patients was 34%. On multivariate analyses, chronic GVHD was significant for relapse (hazard ratio of 1.7, P < 0.05), and for overall survival (hazard ratio 1.4, P < 0.001). Chemosensitivity was significant for relapse only on univariate analysis. Patients who developed chronic GVHD had 4 years median survival, compared with 9 months in patients without chronic GVHD, P < 0.001. The study shows that patients with chronic GVHD have superior survivals, most probably related to a graft-versus-lymphoma effect, which could be modulated by prophylactic T cell infusion.
52例难治性淋巴瘤患者在接受T细胞清除的异基因骨髓移植后,前瞻性地接受了预防性T淋巴细胞输注,以诱导移植物抗淋巴瘤效应。33例患者有相关供者;19例有无关供者。在移植含有0.8±0.4×10⁵ CD3⁺细胞/kg的骨髓后,若未出现≥Ⅱ级急性移植物抗宿主病(GVHD),则在3个月内给予高达1.75×10⁶ CD3⁺细胞/kg的T细胞。Ⅱ-Ⅳ级急性GVHD的累积发生率为69%。32例可评估患者中有20例(63%)发生了慢性GVHD。10例患者(19%)死于GVHD。所有患者的Kaplan-Meier 5年总生存率为34%。多因素分析显示,慢性GVHD对复发有显著影响(风险比为1.7,P<0.05),对总生存也有显著影响(风险比1.4,P<0.001)。仅单因素分析显示化疗敏感性对复发有显著影响。发生慢性GVHD的患者中位生存时间为4年,而未发生慢性GVHD的患者为9个月,P<0.001。该研究表明慢性GVHD患者有更好的生存率,很可能与移植物抗淋巴瘤效应有关,这可通过预防性T细胞输注来调节。