Bosanquet A G, McCann S R, Crotty G M, Mills M J, Catovsky D
Bath Cancer Research Unit, Royal United Hospital, UK.
Acta Haematol. 1995;93(2-4):73-9. doi: 10.1159/000204115.
The effect of methylprednisolone on fresh cells from patients with chronic lymphocytic leukaemia (CLL) has been studied using the differential staining cytotoxicity (DiSC) assay resulting in LC90s of < or = 0.2 to 2,000 micrograms/ml. Cells from previously treated patients were, on average, significantly more sensitive to methylprednisolone than those from untreated patients (mean LC90 = 5.7 micrograms/ml, n = 61 vs 31.0 micrograms/ml, n = 17, respectively; p < 0.05). Twelve patients with advanced disease were given high-dose methylprednisolone (1 g/m2/day i.v. x 5 days). In 7 cases, > or = 3 courses were given; 3 patients did not respond (2 achieved palliation) and 4 (57%) achieved a good partial response. These latter 4 patients were all clinically resistant to chlorambucil and anthracyclines and 2 were resistant to fludarabine. In 5 cases, 1 or 2 courses were given but no patients responded. The 8 nonresponders survived a median of 3.5 months whilst the responders have survived a median of 28.5+ months (3 of 4 still alive). This work suggests a rationale for why CLL patients resistant to standard chemotherapy may benefit from high-dose methylprednisolone therapy. Due to cost and toxicity associated with therapy, the decision to treat would be best made on the basis of a DiSC assay result. This pilot study requires confirmation with a well-designed controlled clinical trial.
使用差异染色细胞毒性（DiSC）试验研究了甲泼尼龙对慢性淋巴细胞白血病（CLL）患者新鲜细胞的作用，得出的半数致死浓度（LC90）为≤0.2至2000微克/毫升。先前接受过治疗的患者的细胞平均而言比未接受治疗的患者的细胞对甲泼尼龙更敏感（平均LC90分别为5.7微克/毫升，n = 61和31.0微克/毫升，n = 17；p<0.05）。12例晚期疾病患者接受了高剂量甲泼尼龙治疗（1克/平方米/天，静脉注射，共5天）。7例患者接受了≥3个疗程的治疗；3例患者无反应（2例病情缓解），4例（57%）获得良好部分缓解。后4例患者对苯丁酸氮芥和蒽环类药物均临床耐药，2例对氟达拉滨耐药。5例患者接受了1或2个疗程的治疗，但无患者有反应。8例无反应者的中位生存期为3.5个月，而有反应者的中位生存期为28.5+个月（4例中有3例仍存活）。这项研究为对标准化疗耐药的CLL患者为何可能从高剂量甲泼尼龙治疗中获益提供了理论依据。由于治疗相关的成本和毒性，治疗决策最好基于DiSC试验结果做出。这项初步研究需要通过精心设计的对照临床试验来证实。
