Therapy of Sepsis Syndrome with Human Polyclonal IgM-Enriched Immunoglobulins: Interim Analysis of a Randomized Trial in Neutropenic Cancer Patients

Abstract

Sepsis is a major cause of death in neutropenic cancer patients. We have shown the prognostic significance of endotoxin plasma levels in neutropenic patients with sepsis syndrome, and other groups have suggested the efficacy of polyclonal IgM-enriched immunoglobulins in the treatment of endotoxin-positive sepsis in non-neutropenic patients. To evaluate the efficacy of polyclonal IgM-enriched immunoglobulins in the treatment of sepsis syndrome in neutropenic patients with hematologic malignancies, a randomized, placebo-controlled trial was initiated at our institutions. The patients were randomly assigned to either the human polyclonal immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 1 with 49.4 g IgG, 7.8 g IgM, 7.8 g IgA) or the equivalent dose of 5% human albumin. In the 52 entered patients with sepsis syndrome followed to death or day 28, there were ten deaths among the 22 recipients of albumin (46%) and nine deaths among the 30 recipients of immunoglobulin (30%; p>0.05). In the subgroup of patients with sepsis syndrome but without shock at entry, the mortality was 11% (one of nine) in the albumin and 12% two of seventeen in the immunoglobulin group. However, the immunoglobulin administration reduced mortality from 69% nine of thirteen to 54% (seven of thirteen) in the subgroup of patients with shock at entry and from 89% to 67% in the subgroup of patients with organ failure at entry, (acute lung, renal or hepatic failure or disseminated intravascular coagulation). This interim analysis suggests that human polyclonal IgM-enriched immunoglobulins may reduce the mortality from sepsis syndrome in neutropenic cancer patients. A completion of the ongoing trial is needed to substantiate these findings taking into account that randomization has to be stratified for sepsis syndrome with and without septic shock at entry because of the different risk of death.