Arora Mukta, Burns Linda J, Davies Stella M, Macmillan Margaret L, Defor Todd E, Miller Wesley J, Weisdorf Daniel J
Department of Medicine, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota, USA.
Biol Blood Marrow Transplant. 2003 Jan;9(1):38-45. doi: 10.1053/bbmt.2003.50003.
Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT). We studied 159 patients with CGVHD longitudinally to characterize the natural history of CGVHD and identify reliable predictors of response and long-term mortality. Rates of response to treatment were 61%, 53%, and 50% at 6 months, 1 year, and 2 years, respectively. A high incidence of infections (7 of 1,000 patient-days at 0 to 6 months, 2.5 of 1,000 patient-days at 6 months to 1 year, and 0.6 of 1,000 patient-days at 1 to 2 years) was observed. After a median follow-up of 8.4 years, an overall survival rate of 40% was observed. The overall survival rate was 63% (95% confidence interval [CI], 56%-71%) at 1 year, 51% (95% CI, 43%-59%) at 2 years, and 39% (95% CI, 31%-47%) at 10 years. In multivariate analysis, age older than 20 years (RR = 1.5; 95% CI, 0.9%-2.5%; P =.09), progressive onset of CGVHD (RR = 1.6; 95% CI, 1.0%-2.4%; P =.04), platelet count of <100,000/ microL (RR = 2.1; 95% CI, 1.3%-3.4%; P =.001), and GI involvement (RR = 1.5; 95% CI, 1.0%-2.4%; P =.05) were associated with increased mortality. Among patients surviving more than 6 months, no response (RR = 4.5; 95% CI, 1.9%-10.5%; P =.0006) and partial response (RR = 2.5; 95% CI, 1.1%-6.1%; P =.04) to treatment at 6 months also were significant predictors of mortality. The prevalence of active CGVHD was 33% at 2 years. However, the cumulative incidence of successful discontinuation of therapy was only 13% at 2 years. Among patients with clinical resolution of CGVHD, only 18% were off immunosuppressive therapy by 2 years, and 89% by 4 years. Despite high initial response rates, a large majority of patients had active disease requiring prolonged immunosuppression. This requires improved infection prevention for a longer time. Recognition of a high-risk group should facilitate assignment of more intensified regimens. Better treatment regimens need to be identified to improve survival and limit toxicity of prolonged immunosuppression.
慢性移植物抗宿主病（CGVHD）是异基因骨髓移植（BMT）后发病和死亡的主要原因。我们对159例CGVHD患者进行了纵向研究，以描述CGVHD的自然病程，并确定反应和长期死亡率的可靠预测因素。治疗反应率在6个月、1年和2年时分别为61%、53%和50%。观察到感染发生率较高（0至6个月时为每1000个患者日7例，6个月至1年时为每1000个患者日2.5例，1至2年时为每1000个患者日0.6例）。中位随访8.4年后，观察到总体生存率为40%。1年时总体生存率为63%（95%置信区间[CI]，56%-71%），2年时为51%（95%CI，43%-59%），10年时为39%（95%CI，31%-47%）。多变量分析显示，年龄大于20岁（RR = 1.5；95%CI，0.9%-2.5%；P =.09）、CGVHD进展性发病（RR = 1.6；95%CI，1.0%-2.4%；P =.04）、血小板计数<100,000/微升（RR = 2.1；95%CI，1.3%-3.4%；P =.001）以及胃肠道受累（RR = 1.5；95%CI，1.0%-2.4%；P =.05）与死亡率增加相关。在存活超过6个月的患者中，6个月时对治疗无反应（RR = 4.5；95%CI，1.9%-10.5%；P =.0006）和部分反应（RR = 2.5；95%CI，1.1%-6.1%；P =.04）也是死亡率的重要预测因素。2年时活动性CGVHD的患病率为33%。然而，2年时成功停药的累积发生率仅为13%。在CGVHD临床缓解的患者中，2年时只有18%停用了免疫抑制治疗，4年时为89%。尽管初始反应率较高，但大多数患者仍有活动性疾病，需要长期免疫抑制治疗。这需要在更长时间内加强感染预防。识别高危人群应有助于分配更强化的治疗方案。需要确定更好的治疗方案，以提高生存率并限制长期免疫抑制的毒性。
