Low activity of the classical complement pathway predicts short survival of patients with chronic lymphocytic leukaemia

Abstract

SUMMARY The activities of the classical (CP) and alternative (AP) complement pathways as well as the levels of some complement components and circulating immune complexes were measured in 43 patients with chronic lymphocytic leukaemia (CLL) between 1980 and 1984. Depressed C P activities were frequently found in these patients. Clinical course of the disease in the patients was followed until 1992, and compared with the initial complement values. During the follow-up period 36 patients died, death of 33 patients being related to the underlying disease. A strong positive correlation (P < 0.01) was found between the length of survival of the patients and the initial CP values. Patients were divided into two groups: group A, short-term survivors, i.e patients who died in CLL-related complications within 3 years after the complement measurements; and group B, long-term survivors who died ≥ 4 years after the complement measurements due to any cause, or were alive at the end of the follow-up period. Average CP values in Group B were almost twice those in group A (P= 0.002), and a similar but less pronounced difference was found in C3 levels (P= 0.055). These differences were even more marked (P= 0 0006 and P= 0.0015, respectively) when only patients in Rai stage 2 and 3 were considered. Low classical pathway activities predicted short survival time: according to the logrank test, patients in Rai stage 2–3 with low (< mean − 2 s.d. of the normal values), and normal CP levels survived for 2.0 ± 1.1, and 4.6 ± 3.0 years, respectively. All the nine and 11/13 patients with low CP and C4 levels, respectively, died within 3 years after the complement measurements were made. These findings indicate that complement measurements performed in CLL patients have a clinical value.