Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Accelerates Neutrophil Regeneration and Reduces the Number of Bacterial Infections after Autologous Bone Marrow Transplantation
H. Link    
Zander AR, Barlogie B (eds) Autologus Bone Marrow Transplantation for Hodgkin`s Diseases,
Non-Hodgkin`s Lymphoma and Multiple Myeloma,Springer-Verlag, Berlin Heidelberg New York London
Infections during granulocytopenia are a major complication of autologous bone marrow transplantation [2, 5]. Since recombinant human granulocytemacrophage colony-stimulating factor (rhu-GM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy [1] and autologous bone marrow transplantation (ABMT) [3, 4], we studied its effects on hematopoietic regeneration and on infectious complications in a controlled trial.
This was a prospective placebo-controlled double-blind study in 21 centers for BMT in Europe and Israel. A total of 81 patients with acute lymphoblastic leukemia in complete remission or with non-Hodgkin's lymphoma were treated after total-body irradiation of at least 8 Gy followed by hig-dose chemotherapy. They received either 250 g rhu-GM -CSF/m ( Escherichia coli derived) daily by continous infusion after ABMTor placebo. Treatment was continued until the neutrophil count reached >500 1 for 1 week. The maximum treatment duration, however, was 30 days. The data on 39 patients in the rhu-GM-CSF group and on 40 in the placebo group were evaluable. The median time needed to reach 500 neutrophils/1 was 15 days with rhu-GM-CSF and 28 days with the placebo (p=0.001; Fig. l).Bacterial infections occurred in 14 (35.9 %) of patients treated

Fig.1. Duration of neutropenia after AMBT in patients with and without rhuGM-CSF

Fig.2. Number of patients with infections and bacterial infections after ABMT with and without rhuGM-CSF. p = 0.024

with rhuGM-CSF and in 25 (62.5 %) of patients given the placebo (p=0.024; Fig. 2). Nine of the 14 bacterial infections in the rhuGM-CSFgroup and 20 of the 25 infections in the placebo group were diagnosed within the first 10 days after BMT. The patients were isolated for 26 days (median duration) with rhuGM-CSF and for 30 days with placebo. The side effects of rhuGM-CSF were reversible capillary leakage and a higer rate of reversible fluid retention in five patients. Patients with rhuGM-CSF had lower serum protein and albumin levels than the palcebo group. We conclude that continous infusion of rhuGM-CSFafter autologous BMT accelerates the regeneration of granulocytes and reduces the number of bacterial infections significantly. RhuGM-CSF makes it possible to shorten the duration of patient isolation and has only moderate and reversible acute side effects. RhuGM-CSF (E. coli) may be useful in reducing the immediate infectious complications of this aggressive high-dose antitumor therapy and become an important supportive therapy.


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