Generation of the complement activation product C5a precedes interleukin-2-induced capillary leakage syndrome.
Capillary leakage syndrome (CLS) is a severe side effect of intravenous interleukin-2 (IL-2) therapy. Twenty-seven cycles of IL-2 therapy [six (day 1), nine (day 2), and 12 >( 10(6) U/m(2) body surface (days 3 to 5), given as continuous infusion] were analyzed in children and adolescents. The anaphylatoxin C5a was assessed as an early predictor for CLS. CLS developed in 11 of 27 cycles of IL-2 infusion. C5a at day 2 of IL-2 infusion (0.8-9.43 mu g/L; median, 1.8 mu g/L) was increased in CLS patients when compared with baseline values (0.21-0.74 mu g/L; median, 0.40 mu g/L; p = 0.01) and when compared with C5a at day 2 in non-CLS patients (0.44-1.2 mu g/L; median, 0.62 mu g/L; p <0.01). Ten of 11 CLS patients showed C5a levels >1.0 mu g/L, whereas 14 of 16 patients who did not develop CLS showed C5a <1.0 mu g/L (predictive value positive 83% for CLS).
Nurnberger
W
W
Department of Pediatric Hematology, Heinrich Heine University Medical Center, Dusseldorf, Germany.
Holthausen
S
S
Michelmann
I
I
Jurgens
H
H
Burdach
S
S
Gobel
U
U
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D019559:Capillary Leak Syndrome / Q000209:etiology* / Q000276:immunology; D002648:Child; D015936:Complement C5a / Q000096:biosynthesis*; D003171:Complement Pathway, Classical / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; D015936:Complement C5a