反应停治疗难治复发多发性骨髓瘤疗效观察及其对细胞免疫功能的影响

The clinical efficacy of thalidomide therapy in refractory or relapsed multiple myeloma and the change of cellular immune function

目的：探讨反应停治疗难治复发多发性骨髓瘤（RRMM）的疗效与细胞免疫功能的变化。方法：对26例RRMM患者给予连续6个月以上反应停治疗，在反应停治疗前后检测T细胞亚群、NK细胞及血清IL-2、IFN-7、TNF—α水平的变化。结果：3例患者因不良反应停药，反应停治疗RRMM的总有效率为60．9%（14／23）。患者反应停治疗前CD4^＋T细胞（30．89±5．92）％、NK细胞（12．31±3．28）％、CD4／CD8比值（0．76±0．18）以及血清IL-2（88．91±19．57）ng／L、IFN-γ（78．53±28．47）ng／L，均显著低于正常对照组（均P〈0．01），CD8^＋T细胞（41．83±7．99）％、TNF—α（127．73±25．09）ng／L，显著高于正常对照组（均P〈0．01）。反应停治疗有效的患者CD4^＋T细胞、NK细胞、CD4／CD8比值以及血清IL-2、IFN-γ／水平治疗后逐渐上升，CD8^＋T细胞、TNF—α逐渐下降，治疗前后对比均差异有统计学意义（均P〈0．01），反应停治疗无效的患者治疗前后对比均差异无统计学意义（均P〉0．05）。结论：反应停治疗RRMM有效且不良反应小，它可能通过调节体内细胞免疫反应发挥抗瘤作用。

Objective： To investigate the change of cellular immune function of the patients with refractory or relapsed multiple myeloma before and after treatment with thalidomide. Method： The study involved 26 patients with relapsed or refractory multiple myeloma who were qualified to thalidomide treatment. They received thalidomide treatment for consecutive 6 months or more. We measured the CD4^± cell,CD8^± cell, CD56^± cell, CD4/CD8 in peripheral blood and the serum levels of IL-2, IFN-γ, TNF-α at 0, 3, 6 months after treatment with thalidomide. Result：23 cases could be analyzed except 3 patients who withdraw from the study because of severe sideeffects of thalidomide. The total response rate was 60.9% （14/23）. Before therapy the CD4^± cell, CD8^± cell, CD56- cell, CD4/CD8 in the peripheral blood and the serum levels of IL-2, IFN-γ, TNF-α were 30.89 ± 5.92%, 41.83±7.99%, 12.31±3.28%, 0.76±0.18, 88.91±19.57 ng/L, 78.53±28.47 ng/L and 127.73±25.09 ng/ L,respectively. The CD4^＋ cell, CD56^- cell, CD4/CD8 and the serum levels of IL-2, IFN-γ were significantly lower in patients with relapsed or refractory multiple myeloma than those in normal healthy individuals （ P 〈 0.01）, but the CD8 ^＋cell and TNF-α were higher than normal healthy individuals （ P 〈0.01）. We found the significant increase of CD4^＋ cell, CD56^＋ cell, CD4/CD8, IL-2, IFN-γ and decrease of CD8^＋ cell, TNF-α in patients responding to thalidomide after 3 or 6 months of therapy （ P 〈0.01）. But no significant change of cellular immune function was seen in those failing to respond to thalidomide （ P 〈0.05）. Conclusion： Thalidomide was active and mild side-effect agents against advanced myeloma. It may induce anti-tumor effects through adjusting cellular immune function.