Fefer A, Benyunes M, Higuchi C, York A, Massumoto C, Lindgren C, Buckner C D, Thompson J A
Division of Oncology, University of Washington, Seattle.
Acta Haematol. 1993;89 Suppl 1:2-7. doi: 10.1159/000204577.
Patients who undergo autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies experience a high relapse rate. Therapy with interleukin-2 (IL-2) +/- lymphokine-activated killer (LAK) cells has induced clinical responses in some patients with advanced malignant lymphoma (ML) or acute myelogenous leukemia (AML). It is postulated that IL-2 +/- LAK cells represents a potentially non-cross-resistant therapeutic modality which might prevent or delay relapses if used as consolidative immunotherapy after ABMT, at a time of minimal residual disease. Therefore, we first studied the reconstitution of IL-2-responsive LAK precursor cells after ABMT and found them in the circulation as early as 3 weeks after ABMT. A phase Ib clinical trial was then performed which identified a tolerable IL-2 regimen which could be administered early after ABMT and which could induce immunomodulatory effects. We then initiated a clinical trial to determine the feasibility of generating and administering autologous LAK cells using this IL-2 regimen after ABMT for 16 patients with ML. The results show that IL-2+LAK therapy early after ABMT is feasible but is more toxic than IL-2 alone. Patients with AML on the phase I IL-2 trial and with ML on the IL-2+LAK protocol were evaluated for tumor status. Of 8 patients with AML in first relapse or at a later stage who underwent ABMT and received IL-2, 2 have relapsed, while 6 remain in complete remission 26+ to 40+ (median 28+) months after ABMT. Of 16 patients with ML considered at high risk for relapse who were treated with ABMT+IL-2+LAK, 5 have relapsed, while 11 remain in complete remission at 6+ to 21+ (median 10+) months after ABMT. The results in both trials are quite encouraging and appear to be better than those in nonrandomized historical controls at our institution. Prospectively randomized trials of IL-2 versus no IL-2 after ABMT in such patients are being initiated to assess definitively the effect, if any, on the relapse rate.
接受自体骨髓移植（ABMT）治疗晚期血液系统恶性肿瘤的患者复发率很高。白细胞介素-2（IL-2）联合或不联合淋巴因子激活的杀伤细胞（LAK）进行治疗，已在一些晚期恶性淋巴瘤（ML）或急性髓性白血病（AML）患者中诱导出临床反应。据推测，IL-2联合或不联合LAK细胞代表一种潜在的非交叉耐药治疗方式，如果在ABMT后微小残留病阶段用作巩固性免疫治疗，可能预防或延迟复发。因此，我们首先研究了ABMT后IL-2反应性LAK前体细胞的重建情况，发现最早在ABMT后3周它们就出现在循环中。随后进行了一项Ib期临床试验，确定了一种可耐受的IL-2方案，该方案可在ABMT后早期给药，并可诱导免疫调节作用。然后我们启动了一项临床试验，以确定在ABMT后使用该IL-2方案为16例ML患者制备和给予自体LAK细胞的可行性。结果表明，ABMT后早期进行IL-2+LAK治疗是可行的，但毒性比单独使用IL-2更大。对I期IL-2试验中的AML患者和IL-2+LAK方案中的ML患者进行了肿瘤状态评估。在8例首次复发或晚期接受ABMT并接受IL-2治疗的AML患者中，2例复发，而6例在ABMT后26 +至40 +（中位28 +）个月仍处于完全缓解状态。在16例被认为复发风险高的ML患者中，接受ABMT+IL-2+LAK治疗，5例复发，而11例在ABMT后6 +至21 +（中位10 +）个月仍处于完全缓解状态。两项试验的结果都相当令人鼓舞，似乎比我们机构非随机的历史对照结果更好。正在启动前瞻性随机试验，比较此类患者ABMT后使用IL-2与不使用IL-2的情况，以明确评估对复发率的影响（如果有）。
