C1 ESTERASE INHIBITOR CONCENTRATE FOR CAPILLARY LEAKAGE SYNDROME FOLLOWING BONE-MARROW TRANSPLANTATION

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 (CI INH) acitivity 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 (tachyc ardia and/or decreased blood pressure), and non-responsiveness to furo semide. Of 142 patients, 22 developed severe CLS. The first seven pati ents whom we diagnosed with this complication were assessed as control patients. Fifteen patients with severe CLS were treated with CI INH c oncentrate using a cumulative dose of 180 units/kg body wt. (initial d ose: 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 wa s 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 leve ls of the complement activation parameters C4d and C5a were 3 +/- 1.1 mg/dl (mean +/- S.D.) and 0.3 +/- 0.1 mu g/l, respectively, prior to B MT, increasing to 8.2 +/- 2.1 mg/dl and 1.3 +/- 0.4 mu g/l, respective ly, at diagnosis of CLS. After infusion of C1 INH concentrate the plas ma levels of C5a and C4d normalized. The activity of C1 INH rose to 13 9 +/- 10% of normal human plasma NHP pool (mean+/-S.D.) after infusion . The CH50 values were not significantly altered. The fluid status nor malized within 11 days in 14 of 15 treated patients. The results of th is study suggest that therapy with C1 INH concentrate improves the pro gnosis of patients with CLS after BMT. This has to be confirmed in a r andomized, controlled trial.