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白细胞介素-2在急性白血病的治疗中起作用吗?

Does interleukin-2 have a role in the management of acute leukemia?

作者信息

Foa R

机构信息

Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione di Clinica Medica, Torino, Italy.

出版信息

J Clin Oncol. 1993 Sep;11(9):1817-25. doi: 10.1200/JCO.1993.11.9.1817.

Abstract

PURPOSE

To discuss the possibility that interleukin-2 (IL-2)-based immunotherapeutic protocols may have a role in the management of acute leukemia.

DESIGN

The preclinical results that have led to the clinical use of IL-2 in acute leukemia will be reviewed. The clinical data obtained with the administration of IL-2 to acute leukemia patients in different phases of their disease will be discussed, together with the clinicohematologic and immunologic modifications induced following the infusion of IL-2. Finally, the possibility that limitations associated with the exogenous administration of high-dose IL-2 may be circumvented by engineering techniques aimed at inserting the IL-2 gene directly into the tumor cells, will be addressed.

RESULTS

The data indicate that high-dose IL-2 may be administered to acute leukemia patients. Toxicity, recorded in all patients, appears to be controllable using a continuous intravenous (i.v.) infusion protocol based on a daily dose-escalating administration. Complete remissions have been documented in acute myeloid leukemias (AMLs) with a limited, but detectable proportion of residual marrow blasts. Numerous phenotypic and functional changes have been recorded within the immune system of the host. Using retroviral vectors, the IL-2 gene may be productively transduced into human acute leukemia cell lines.

CONCLUSION

IL-2 appears to represent a therapeutic option for AML patients with limited/minimal residual disease. The results of the ongoing randomized trials in patients in first or second remission are awaited.

摘要

目的

探讨基于白细胞介素-2(IL-2)的免疫治疗方案在急性白血病治疗中发挥作用的可能性。

设计

回顾导致IL-2在急性白血病中临床应用的临床前研究结果。讨论在急性白血病患者疾病不同阶段给予IL-2所获得的临床数据,以及输注IL-2后引起的临床血液学和免疫学改变。最后,探讨通过旨在将IL-2基因直接插入肿瘤细胞的工程技术能否规避与外源性给予高剂量IL-2相关的局限性。

结果

数据表明可对急性白血病患者给予高剂量IL-2。所有患者均记录到毒性反应,采用基于每日剂量递增给药的持续静脉输注方案,毒性反应似乎可控。在急性髓系白血病(AML)患者中已记录到完全缓解,残留骨髓原始细胞比例有限但可检测到。在宿主免疫系统内记录到许多表型和功能变化。利用逆转录病毒载体,IL-2基因可有效转导至人急性白血病细胞系。

结论

对于残留疾病有限/极少的AML患者,IL-2似乎是一种治疗选择。正在等待对首次或第二次缓解期患者进行的随机试验结果。

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