CYTOKINE EFFICIENCY IN THE TREATMENT OF HIGH-GRADE MALIGNANT NON-HODGKINS-LYMPHOMAS - RESULTS OF A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED STUDY WITH INTENSIFIED COP-BLAM + - RHGM-CSF/

In high-grade malignant non-Hodgkin's lymphomas (hNHL) recombinant hum an granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was eva luated as support to chemotherapy. In a phase III trial, 172 patients (age 18-73 years, stage II-IV) were risk-stratified according to LDH l evels and lymphoma size and randomized to receive rhGM-CSF (400 mug) ( 87 patients) or placebo (85 patients) subcutaneously days 8-14 of each cycle of an intensified COP-BLAM regimen. RhGM-CSF significantly redu ced the length and nadir of neutropenia, the length of fever episodes, the frequency of all and of severe infections, and of hospitalization and antibiotic requirements. Complete response rates were 63% for all patients and 64% vs. 61% (n.s.) in the rhGM-CSF vs. the control group . Deviations from protocol in applied dosages of myelotoxic drugs and in cycle intervals maintained differed slightly in favor of the rhGM-C SF arm. However, there were no significant differences in overall surv ival between the GM-CSF treatment and control groups (21 vs. 23 months ). Early relapse rates were markedly lower than in the standard-dose C OP-BLAM/IMVP-16 regimen. Thus, GM-CSF abates toxic side effects of che motherapy and may help to maintain dose intensity in high-risk hNHL.