Mackay I R, Goodyear M D, Riglar C, Penschow J, Whittingham S, Russell I S, Kitchen P R, Collins J P
Cancer. 1984 Jun 15;53(12):2619-27. doi: 10.1002/1097-0142(19840615)53:12<2619::aid-cncr2820531209>3.0.co;2-d.
Thirty patients with histologically proven node-positive early breast cancer (Stage II) were treated by total mastectomy and axillary clearance and adjuvant chemotherapy regimens including melphalan for 1 year. These patients were studied sequentially, at 3-month intervals, for up to 2 years to assess effects of cytotoxic drugs on immune function, and to determine whether any changes in immune function were related to recurrence. All indices were in the normal range before chemotherapy. The most marked and long-lasting effects of chemotherapy were on numbers of circulating T-cells and B-cells. Mean counts +/- one standard error (X 10(6)/ml) for T-cells before and 12 months after stopping chemotherapy were 1.537 +/- 0.118 and 0.874 +/- 0.120 (P less than 0.01), and for B-cells 0.345 +/- 0.060 and 0.207 +/- 0.030 (P less than 0.01). Functional indices of T-cell and B-cell competence were less compromised than values for cell counts and, in contrast, recovery occurred either during or within 3 months of stopping chemotherapy. This held for both T-cell function measured by delayed-type hypersensitivity (DTH) responsiveness to five recall antigens and mitogenic responsiveness to phytohemagglutinin, and for B-cell function measured by titration of blood group isohemagglutinins. After 4 years the 30 subjects were divided into groups according to whether there was recurrence of cancer (14) or no recurrence (16); the only index predictive of recurrence was depression of DTH to recall antigens. Thus it was found that cytotoxic chemotherapy with melphalan appears to cause long-lasting depression of cell counts but only short-lasting depression of functional indices of immunocompetence, and that levels of immunologic indices during chemotherapy are mostly nonpredictive of recurrence of cancer. The results prompt some caution in the use of adjuvant chemotherapy, at least with melphalan.
30例经组织学证实为淋巴结阳性的早期乳腺癌（II期）患者接受了全乳切除术、腋窝清扫术以及为期1年的包含美法仑的辅助化疗方案。对这些患者进行连续研究，每隔3个月进行一次，持续长达2年，以评估细胞毒性药物对免疫功能的影响，并确定免疫功能的任何变化是否与复发有关。化疗前所有指标均在正常范围内。化疗最显著且持久的影响是对循环T细胞和B细胞数量的影响。化疗前及化疗结束后12个月T细胞的平均计数±一个标准误（×10⁶/ml）分别为1.537±0.118和0.874±0.120（P＜0.01），B细胞分别为0.345±0.060和0.207±0.030（P＜0.01）。T细胞和B细胞功能的功能指标受损程度低于细胞计数的值，相反，恢复发生在化疗期间或化疗结束后3个月内。这适用于通过对五种回忆抗原的迟发型超敏反应（DTH）反应性和对植物血凝素的促有丝分裂反应性测量的T细胞功能，以及通过血型同种血凝素滴定测量的B细胞功能。4年后，将30名受试者根据癌症是否复发分为两组（复发组14例，未复发组16例）；唯一能预测复发的指标是对回忆抗原的DTH降低。因此发现，美法仑细胞毒性化疗似乎会导致细胞计数长期降低，但只会导致免疫能力功能指标短期降低，并且化疗期间的免疫指标水平大多不能预测癌症复发。这些结果提示在使用辅助化疗时，至少使用美法仑时应谨慎。
