Blaise D, Viens P, Olive D, Stoppa A M, Gabert J, Pourreau C N, Attal M, Gaspard M H, Mannoni P, Jasmin C
BMT Unit, Institut Paoli Calmettes, Marseille, France.
Eur Cytokine Netw. 1991 Mar-Apr;2(2):121-9.
In vivo use of rIL-2 autologous BMT may be the means of reproducing a kind of "adoptive immunotherapy" from grafted cells after allogeneic BMT. This approach may enhance the spontaneous generation of cytotoxic T-cells and NK cells which are presumably involved in this immunotherapy. Potential risks of such an approach would be to increase the usual toxicity of rIL-2 and to jeopardize the hemopoietic reconstitution. To determine the feasibility of this approach we have treated 19 poor prognosis patients with a succession of autologous BMT followed 78 +/- 12 days later by a continuous infusion of rIL-2. Eighteen million international units (IU) per m2 per day of Proleukine (CETUS, Amsterdam, The Netherlands) were administrated over 6 or 12 days. No patient died of the procedure. Clinical toxicity related to rIL-2 was not increased. Hemopoietic toxicity, significant both for platelets and granulocytes, was transient. Immune stimulation was dramatic for lymphocytes and subpopulations (CD3+ and NK cells) and for cytolytic functions (NK and LAK activity). This trial establishes the feasibility of administration of high doses of rIL-2, 2 months after autologous BMT. In this setting a 6 day period of continuous infusion of 18 million per m2 per day of Proleukine appears to be a regularly tolerable dosage conducting to a major immune activation and invites further studies to determine the clinical impact of such an approach.
体内使用重组白细胞介素-2（rIL-2）自体骨髓移植（BMT）可能是在异基因BMT后从移植细胞中重现一种“过继免疫疗法”的方法。这种方法可能会增强细胞毒性T细胞和自然杀伤（NK）细胞的自发产生，而这些细胞可能参与了这种免疫疗法。这种方法的潜在风险是增加rIL-2的常见毒性并危及造血重建。为了确定这种方法的可行性，我们治疗了19例预后不良的患者，先进行一系列自体BMT，然后在78±12天后持续输注rIL-2。每天每平方米给予1800万国际单位（IU）的普罗白介素（Proleukine，Cetus公司，荷兰阿姆斯特丹），持续6天或12天。没有患者死于该治疗过程。与rIL-2相关的临床毒性没有增加。造血毒性对血小板和粒细胞均有显著影响，但为短暂性。对淋巴细胞及其亚群（CD3+和NK细胞）以及细胞溶解功能（NK和淋巴因子激活的杀伤细胞[LAK]活性）的免疫刺激作用显著。该试验证实了自体BMT后2个月给予高剂量rIL-2的可行性。在这种情况下，每天每平方米持续输注1800万IU普罗白介素6天似乎是一个通常可耐受的剂量，可导致主要的免疫激活，并促使进一步研究以确定这种方法的临床影响。
