Nürnberger W, Heying R, Burdach S, Göbel U
Department of Pediatric Hematology and Oncology, Heinrich Heine University Medical Center, Düsseldorf, Germany.
Ann Hematol. 1997 Sep;75(3):95-101. doi: 10.1007/s002770050321.
The prognosis of patients with severe capillary leakage syndrome (CLS) after bone marrow transplantation (BMT) is dismal despite aggressive use of intensive care therapy. Because the activated classical pathway of complement and relatively low levels of C1 esterase inhibitor (C1 INH) activity are known features in these patients, we evaluated the efficacy of a therapy using purified, human C1 INH concentrate. Severe CLS was defined as increase in body weight by more than 3% within 24 h combined with generalized edema, impaired hemodynamic system (tachycardia and/or decreased blood pressure), and non-responsiveness to furosemide. Of 142 patients, 22 developed severe CLS. The first seven patients whom we diagnosed with this complication were assessed as control patients. Fifteen patients with severe CLS were treated with C1 INH concentrate using a cumulative dose of 180 units/kg body wt. (initial dose: 60 units/kg, followed by two doses at 30 units/kg and four doses at 15 units/kg, every 12 h). The survival rate of patients with CLS was 57% at 1 year after BMT in the C1 INH treatment group, compared with 14% in the control group (p = 0.008). Eight of 15 treated patients are alive at a median of 9 months (range: 4-55) after BMT. The plasma levels of the complement activation parameters C4d and C5a were 3 +/- 1.1 mg/dl (mean +/- S.D.) and 0.3 +/- 0.1 microgram/l, respectively, prior to BMT, increasing to 8.2 +/- 2.1 mg/dl and 1.3 +/- 0.4 micrograms/l, respectively, at diagnosis of CLS. After infusion of C1 INH concentrate the plasma levels of C5a and C4d normalized. The activity of C1 INH rose to 139 +/- 10% of normal human plasma NHP pool (mean +/- S.D.) after infusion. The CH50 values were not significantly altered. The fluid status normalized within 11 days in 14 of 15 treated patients. The results of this study suggest that therapy with C1 INH concentrate improves the prognosis of patients with CLS after BMT. This has to be confirmed in a randomized, controlled trial.
尽管积极采用重症监护治疗，但骨髓移植（BMT）后严重毛细血管渗漏综合征（CLS）患者的预后依然不佳。由于已知这些患者存在补体经典途径激活以及C1酯酶抑制剂（C1 INH）活性相对较低的情况，我们评估了使用纯化的人C1 INH浓缩物进行治疗的疗效。严重CLS的定义为24小时内体重增加超过3%，同时伴有全身性水肿、血流动力学系统受损（心动过速和/或血压下降）以及对呋塞米无反应。在142例患者中，22例发生了严重CLS。我们将最初诊断出该并发症的7例患者作为对照患者。15例严重CLS患者接受了C1 INH浓缩物治疗，累积剂量为180单位/千克体重（初始剂量：60单位/千克，随后每12小时给予30单位/千克的剂量2次以及15单位/千克的剂量4次）。C1 INH治疗组中CLS患者在BMT后1年的生存率为57%，而对照组为14%（p = 0.008）。15例接受治疗的患者中有8例在BMT后中位9个月（范围：4 - 55个月）存活。BMT前补体激活参数C4d和C5a的血浆水平分别为3 ± 1.1毫克/分升（均值 ± 标准差）和0.3 ± 0.1微克/升，在诊断CLS时分别升至8.2 ± 2.1毫克/分升和1.3 ± 0.4微克/升。输注C1 INH浓缩物后，C5a和C4d的血浆水平恢复正常。输注后C1 INH的活性升至正常人血浆（NHP）池正常水平的139 ± 10%（均值 ± 标准差）。CH50值无显著变化。15例接受治疗的患者中有14例在11天内液体状态恢复正常。本研究结果表明，C1 INH浓缩物治疗可改善BMT后CLS患者的预后。这必须在随机对照试验中得到证实。
