Blum J E, de Silva S M, Drachman D B, Order S E
Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD.
Int J Radiat Oncol Biol Phys. 1988 Sep;15(3):547-52. doi: 10.1016/0360-3016(88)90293-3.
Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity. This was accomplished without compromise of the immunosuppressant activity of TLI as demonstrated by comparable allogeneic skin graft survival times between the two 3400 cGy treatment groups. This clinical advantage would prove to be beneficial where immediate suppression of the immune system is desirable.
全身淋巴照射（TLI）在实验和临床应用中已成功诱导免疫抑制。然而，TLI的实验和临床应用均受到所需较长治疗疗程的阻碍（大鼠为23天，人类为30 - 60天）。低剂量率TLI有可能在实现相当免疫抑制的同时缩短总体治疗时间。本研究考察常规剂量率（23天）与低剂量率（2 - 7天）TLI的免疫抑制活性和治疗毒性。将七组Lewis大鼠用60Co进行TLI治疗。一组以常规剂量率（80 - 110 cGy/分钟）治疗，在23天内分17次接受3400 cGy照射。六组以低剂量率（7 cGy/分钟）治疗，在2 - 7天内分别接受800、1200、1800、2400、3000和3400 cGy的总剂量照射。以常规剂量率在23天内治疗以及以低剂量率在2 - 7天内治疗的大鼠对辐射耐受性良好，毒性极小。使用同种异体（棕色挪威大鼠）皮肤移植存活情况来检测免疫抑制水平。对照动物的同种异体皮肤移植平均保留14天（范围8 - 21天）。接受常规剂量率治疗的动物（23天内3400 cGy）其移植皮肤保留60天（范围50 - 66天）（p小于0.001）。接受低剂量率治疗的大鼠（2 - 7天内总剂量800至3400 cGy）在TLI后同种异体移植存活时间也有延长，并建立了剂量反应曲线。3400 cGy低剂量率组的移植存活时间（66天，范围52 - 78天）与3400 cGy常规剂量率组无显著差异（p小于0.10）。当给予的总剂量相等时，与常规剂量率TLI相比，低剂量率TLI显示出总体治疗时间缩短的优势（7天对23天）且毒性未增加。两个3400 cGy治疗组的同种异体皮肤移植存活时间相当，这表明低剂量率TLI在不损害其免疫抑制活性的情况下实现了这一优势。在需要立即抑制免疫系统的情况下，这种临床优势将被证明是有益的。
