Capillary leakage syndrome (CIS) after hematopoetic stem cell transplantation (HSCT) - risk factors, differentiation from venoocclus1ve disease (VOD) and treatment approach

CLS is an endothelial disorder and has been described as a severe side effect of intravenous interleukin-2 infusion. Such patients present with massive weight gain, generalized edema, polyserositis, and intravasal volume depletion. We assessed 94 patients after HSCT (unrelated, n - 22; altogeneic-related, n = 35; autologous, n = 37). VOD was diagnosed according to Jones et al. [Transplantation 44 (1987) 778], CLS according to Nürnberger et al. [Ann Hematol 17 (1993) 17]. Nine patients had both VOD and CLS. 6 patients only VOD, 8 patients only CLS; 71 patients under HSCT but with neither diagnosis served as controls Risk factors for CLS were (1) unrelated versus related HSCT [p=0.008]) and (2) the use of total body irradiation, melphatan and etoposide as conditioning regimen in allogeneic-related versus autologous HSCT [p = 0.003]. HLA-Cw7 was found in 55% of patients with CLS, compared to 17% of patients without CLS. CLS was characterized by increased platelet consumption (28±9 units, VOD: 14±5 units), weight gain (increase of 10±3.6% from baseline; VOD: 4.2±2.0%) and complement activation (C5a 1.5±0.4 mg/l; VOD: 0.5±0.4 mg/l). Since the main inhibitor of the classical complement pathway is C1 esterase inhibitor (C1 (NH), 8 patients with CLS underwent treatment with C1 INH-concentrate (180 units/kg). Of those, 7/8 patients responded with normalization of C5a (within 4 hours of C1 INH inlusion). body weight and cardiovascular parameters (within 1 to 5 days, median: 2 days). - In conclusion, alloresponse and complement activation contribute at least in part to the pathophysiology of CLS after HSCT. The main clinical problems of CLS resolve in the majority of patients after inhibition of the activated complement system by C1 INH concentrate.