Soiffer R J, Murray C, Gonin R, Ritz J
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Blood. 1994 Aug 1;84(3):964-71.
T-cell depletion of donor bone marrow has been associated with an increased risk of disease relapse after allogeneic bone marrow transplantation (BMT). Recombinant interleukin-2 (IL-2), which is capable of increasing the antileukemic activity of peripheral blood lymphocytes obtained from patients who have undergone BMT, has been proposed as a potentially useful agent to reduce the risk of relapse post-BMT. We have previously shown that IL-2 administered to patients at very low doses after BMT is both clinically tolerable and immunologically active. We now report on the clinical outcome of 29 patients treated with low-dose IL-2 after CD6-depleted allogenic BMT for hematologic malignancy. IL-2 was administered by continuous infusion for up to 3 months beginning at a median of 67 days post-BMT. Eligibility requirements for IL-2 therapy included demonstration of stable engraftment and absence of acute grade 2-4 graft-versus-host disease (GVHD). Low-dose IL-2 was well tolerated by the majority of patients, with only 4 of 29 subjects withdrawn early. Acute GVHD developed in only one individual. After 12 weeks of treatment, the mean number of circulating natural killer cells in patients increased 10-fold without any significant change in T-cell number. Of the 25 patients who received > or = 1 month of IL-2, only 6 have relapsed. Relapse rate and disease-free survival (DFS) were determined in the 25 patients who completed at least 4 weeks of IL-2 treatment and compared with historical controls transplanted at our institution for the same conditions and treated with an identical ablative regimen and method of T-cell depletion. Only control patients who had survived disease free for 100 days post-BMT were included in this analysis. Cox's proportional hazards regression model suggested that, compared with control patients without a history of GVHD, patients treated with IL-2 had a lower risk of disease relapse (hazard ratio 0.34; range, 0.14 to 0.82) and superior DFS (hazard ratio 0.39; range 0.18 to 0.87). A randomized controlled trial of IL-2 immunotherapy after T-cell-depleted BMT should now be undertaken.
供体骨髓的T细胞清除与异基因骨髓移植（BMT）后疾病复发风险增加有关。重组白细胞介素-2（IL-2）能够增强接受BMT患者外周血淋巴细胞的抗白血病活性，已被提议作为一种潜在有用的药物来降低BMT后复发风险。我们之前已表明，BMT后以极低剂量给予患者IL-2在临床上是可耐受的且具有免疫活性。我们现在报告29例因血液系统恶性肿瘤接受CD6清除的异基因BMT后接受低剂量IL-2治疗患者的临床结果。IL-2从BMT后中位67天开始持续输注长达3个月。IL-2治疗的入选标准包括证实移植稳定且无2 - 4级急性移植物抗宿主病（GVHD）。大多数患者对低剂量IL-2耐受性良好，29例受试者中只有4例提前退出。仅1例个体发生急性GVHD。治疗12周后，患者循环自然杀伤细胞的平均数量增加了10倍，而T细胞数量无任何显著变化。在接受≥1个月IL-2治疗的25例患者中，仅6例复发。在完成至少4周IL-2治疗的25例患者中确定复发率和无病生存期（DFS），并与在我们机构在相同条件下移植、接受相同预处理方案和T细胞清除方法的历史对照进行比较。该分析仅纳入BMT后无病存活100天的对照患者。Cox比例风险回归模型表明，与无GVHD病史的对照患者相比，接受IL-2治疗的患者疾病复发风险较低（风险比0.34；范围0.14至0.82）且DFS更佳（风险比0.39；范围0.18至0.87）。现在应该进行一项关于T细胞清除的BMT后IL-2免疫治疗的随机对照试验。
