A “Single” Dose of G-CSF after Autologous Stem Cell Transplantation in Patients with Malignant Lymphoma - Third Interim Analysis of Multicentre Randomized Trial Comparing Standard Schedule with Delayed Application and Placebo.

The optimal schedule of G-CSF given after autologous peripheral stem cell transplantation (ASCT) has not been defined yet. Here we present results of the third interim analysis of randomized multicentre trial comparing standard application of G-CSF from day +5 (arm A) with delayed dosing (G-CSF was started when WBC reached 0,5x109/l and neutrophil count 0,1x109/l; arm B) and placebo (arm C). In order to eliminate the influence of diagnosis and conditioning and to minimize the impact of graft quality only patients with malignant lymphoma conditioned by BEAM and with graft harvested in maximum 3 aphereses containing at least 5,0x106 CD 34+cells/kg were included. Patients signed informed consent before registration into the study that had been approved by local ethical and national health care authorities. 115 patients at median age 45 (range 21 – 64) were randomized by July 15th, 2004. The data of 97 patients were analysed. There was no difference in age, lymphoma bone marrow involvement at diagnosis, number of chemotherapy cycles and the use of radiotherapy before transplantation and CD 34+ cells content in graft between any two of the three arms. Duration of neutropenia below 0,5x109/l and 1,0x109/l and number of days to neutrophil engraftment over 0,5x109/l and 1,0x109/l are listed in the table. A significant difference in duration of neutropenia and time to neutrophil engraftment was found between the arms A and B (p=0,002 – 0,005), the arms A and C (p<0,0001) and also between the arms B and C (p=0,04–0,0001). A trend for delayed platelet engraftment was observed in both arms with G-CSF (A and B). Duration of hospitalisation was significantly longer in placebo group (arm C), however, there was no prolongation of fever or antibiotic use. The delayed „single” application of G-CSF (usually with one or two doses sufficient for full neutrophil recovery) appears to be safe and cost effective. Comparing with standard G-CSF schedule only one day delay in median neutrophil engraftment was observed. We hope to finish the study within the year 2004. Supported by the grant MSN 15110004.