CYTOKINE RESPONSE TO INFECTION IN PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA FOLLOWING INTENSIVE CHEMOTHERAPY

Septic shock is the major cause of treatment-related death in patients with acute myelogenous leukaemia (AML) undergoing intensive chemother apy. Interleukins (IL)-1 beta, -6, -8, and tumour necrosis factor alph a (TNF-alpha) have been implicated as mediators of septic shock, with circulating leucocytes being considered a major source for their relea se. However, plasma cytokine levels of leucocytopenic patients with ev olving sepsis have not been studied. We have prospectively measured pl asma cytokines during chemotherapy-induced leucocytopenia (< 1 x 10(9) /1)in 50 patients with AML. Cytokine levels in patients with severe se psis (n = 5) or septic shock (n = 8) were compared to those measured i n 13 matched patients with uncomplicated febrile infections. In evolvi ng septic shock, IL-6, IL-8 and TNP-alpha peaked within 48 h of fever onset at levels reported for nonleucocytopenic patients and distinctiv ely higher than during uncomplicated febrile episodes (P < 0.05). Peak concentrations measured within 48 h after onset of fever were related to fatal outcome. IL-1 beta was detected in less than 5% of all sampl es. Cytokine concentrations were unrelated to leucocyte counts and mar kers of neutrophil or monocyte activation (elastase and neopterin leve ls, respectively). We conclude that cytokine release associated with e volving septic shock in patients with AML does not depend on circulati ng leucocytes.