A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease
A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease
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DOI：
10.1053/bbmt.2001.v7.pm11669216
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Vogelsang, GB
中科院分区：
文献类型：
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作者：
Akpek, G;Lee, SM;Vogelsang, GB
皮质类固醇对于控制活动性慢性移植物抗宿主病（cGVHD）仍然至关重要。然而，最佳剂量和给药方案尚不清楚。我们回顾了61例重度难治性cGVHD患者的治疗结果，这些患者接受了高剂量脉冲类固醇方案（PS）治疗，即连续4天每天给予甲泼尼龙10mg/kg，随后逐渐减量。4天后，所有患者都接受了一个疗程的额外免疫抑制治疗。可评估疗效的56例患者的中位年龄为32岁（范围0.2 - 57岁）。在接受PS治疗前，患者平均接受过2种（范围1 - 5种）治疗但均失败。PS治疗后45例存活患者的中位随访时间为1.5年。PS治疗后1年和2年的生存率分别为88%（95%置信区间[CI]，76% - 95%）和81%（95%CI，65% - 91%）。27例患者（48%）对PS有显著反应，cGVHD症状有实质性改善，包括皮肤变软、活动范围增加和身体功能状态改善；15例患者（27%）有轻微反应，即cGVHD的部分但非所有症状有所改善。在42例有反应的患者中，21例（50%）之后cGVHD病情进展。进展的中位时间为1.9年。PS治疗后1年和2年病情进展的概率分别为36%（95%CI，23% - 53%）和54%（95%CI，38% - 71%）。有显著反应和轻微反应的患者在1年时病情进展的概率分别为25%（95%CI，12% - 47%）和55%（95%CI，32% - 81%）（风险比为2.13）。42例有反应的患者中有10例（24%）能够停止所有全身性免疫抑制治疗。PS治疗后1年和2年停止治疗的概率分别为9%（95%CI，3% - 25%）和27%（95%CI，15% - 48%）。该治疗耐受性良好，无严重不良事件。我们的结果表明，PS是一种耐受性良好的方案，可使大多数既往多种治疗失败的cGVHD患者迅速获得临床反应。有必要进一步研究通过与治疗cGVHD的新型活性药物联合来维持该方案的疗效。
Corticosteroids remain essential for controlling active chronic graft-versus-host disease (cGVHD). However, the optimum dose and administration schedule is unknown. We have reviewed our results in 61 patients with severe refractory cGVHD who were treated with a high-dose pulse steroid regimen (PS) consisting of methylprednisolone at 10 mg/kg per day for 4 consecutive days, with subsequent tapering doses. After 4 days, all patients received a course of additional immunosuppressive therapy. The median age of the 56 patients who were evaluable for response was 32 years (range, 0.2-57 years). Patients had failed a median of 2 (range, 1-5) treatments prior to the PS. The median follow-up for 45 surviving patients after PS was 1.5 years. The probability of survival at I year and 2 years after PS was 88% (95% confidence interval [CI], 76%-95%) and 81% (95% Cl, 65%-91%), respectively. Twenty-seven patients (48%) showed a major response to PS with substantial improvement of cGVHD manifestations, including softening of the skin, increased range of motion, and improved performance status; 15 patients (27%) showed a minor response, defined as improvement in some but not all symptoms of cGVHD. Of the 42 responders, 21 (50%) had progression of their cGVHD afterwards. The median time to progression was 1.9 years. The probability of progression at I and 2 years after PS was 36% (95% CI, 23%-53%) and 54% (95% CI, 38%-71%), respectively. The probability of progression at 1 year was 25% (95% CI, 12%-47%) and 55% (95% CI, 32%-81%) for patients who had major and minor response, respectively (hazard ratio, 2.13). Ten of the 42 responders (24%) were able to discontinue all systemic immunosuppressive treatments. The probability of discontinuation at 1 and 2 years after PS was 9% (95% CI, 3%-25%) and 27% (95% CI, 15%-48%), respectively. The treatment was well tolerated with no serious adverse events. Our results suggest that PS is a well-tolerated regimen for achieving rapid clinical response in the majority of patients with cGVHD who failed on multiple previous therapies. Further studies are warranted to maintain the efficacy of this regimen by combining with new active agents in cGVHD.