REGULATED PLASMA-LEVELS OF COLONY-STIMULATING FACTORS, INTERLEUKIN-6 AND INTERLEUKIN-10 IN PATIENTS WITH ACUTE-LEUKEMIA AND NON-HODGKINS-LYMPHOMA UNDERGOING CYTOREDUCTIVE CHEMOTHERAPY

Endogenous plasma levels of granulocyte colony stimulating factor (G-C SF), granulocyte-macrophage colony-stimulating factor (GM-CSF). IL-6 a nd IL-10 were measured in a total of 70 patients undergoing cytoreduct ive chemotherapy for treatment of acute leukaemia or non-Hodgkin's lym phomas. The diagnoses were acute myeloid leukaemia (AML; n = 30), acut e lymphoblastic leukaemia (ALL: n = 6), non-Hodgkin's lymphomas (NHL; n = 11) and other malignant haematological disorders including myelody splastic syndromes (n = 23). After chemotherapy, plasma G-CSF was elev ated (mean 5.6 ng/ml: range 1.2-10ng/ml). and was inversely correlated with white blood cell counts (WBC) (r = -0.7, P < 0.001). Occurrence of fever (T > 38.0 degrees C) during severe myelosuppression (WBC<1x10 (9)/l) was associated with an additional increase of G-CSF levels (P < 0.001). Plasma IL-6 correlated significantly with fever (range <1 to 1100pg/ml, mean 130pg/ml; r=0.5, P < 0.001) but revealed only a weak a ssociation with WBC or platelet counts, In patients treated with recom binant G-CSF (n=9), an association between IL-6 and fever was still ob served after chemotherapy, During the nonfebrile status (total n = 242 ; AML n = 124), IL-6 levels remained < 9 pg/ml in 90% of cases, wherea s G-CSF increased with leucopenia (r = -0.72; P < 0.001). In contrast, endogenous GM-CSF remained normal and IL-IO showed only a slight incr ease (21% of samples: maximum 22 pg/ml) in severe leucopenia. In parti cular, IL-10 levels did not correlate with G-CSF or TL-G levels. We co nclude that systemic release of G-CSF and IL-6 is obviously not abroga ted by cytoreductive chemotherapy in acute leukaemia and NHL and may a dd to the therapeutic efficacy of recombinant cytokines. Also, plasma levels of G-, GM-CSF or IL-6 appear to be regulated by separate mechan isms.