The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]

Abstract

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG- CSF in normal granulocyte donors are warranted.

Ex vivo neutrophil function in response to three different doses of glycosylated rHuG‐CSF (Lenograstim)

“…Granulocyte colony-stimulating factor (G-CSF) is a polypeptide haemopoietic growth factor which selectively stimulates and regulates the proliferation, differentiation and survival of the committed precursor cells of polymorphonuclear leucocytes (PMN) (Demitri & Griffin, 1991;Schwinger et al, 1993). In both neutropenic and nonneutropenic subjects, G-CSF has been found to rapidly increase the number of circulating PMN in a dose-dependent fashion and has therefore been investigated as therapy for patients with various neutropenic conditions (Bensinger et al, 1993;Hollingshead & Goa, 1991). G-CSF has also been shown to potently stimulate or enhance certain effector functions of mature human PMN, these being properties that are primarily related to hose defence against invading pathogens (Demitri & Griffin, 1991).…”

Renewed Interest in Granulocyte Transfusion Therapy

“…What then is the basis for renewed interest in this form of therapy? The most important reasons spurring this revitalized interest are the discovery of the potency of recombinant human G-CSF (rhG-CSF) to elevate blood neutrophil levels in haematologically normal persons and the accumulating evidence that rhG-CSF can be administered to blood donors with few adverse effects (Bensinger et al, 1993;Casper et al, 1995;Leitman et al, 1995Leitman et al, , 1996Liles et al, 1997). G-CSF was first identified as a stimulatory factor present in the serum of animals administered endotoxin (Nicola et al, 1983).…”

“…Second, because the situations in which neutrophil transfusions are needed cannot be readily predicted, it is also important that rhG-CSF works rapidly through accelerated release of preformed cells from the bone marrow. Several studies now show that 300 mg of G-CSF (approximately 5 mg/ kg) can elevate blood neutrophils 5-6-fold in 12-24 h, compared to a 2-3-fold increase after corticosteroid therapy (Bensinger et al, 1993;Caspar et al, 1995;Leitman et al, 1995;Liles et al, 1997). Recent studies have shown that these effects are additive, if not synergistic (Liles et al, 1997).…”

“…Finally, rhG-CSF has a very favourable side-effect profile in donors. Bone pain and headache, neither usually severe, are the only adverse effects frequently encountered (Bensinger et al, 1993;Caspar et al, 1995;Leitman et al, 1995Leitman et al, , 1996Liles et al, 1997;Chatta et al, 1994;Dale et al, 1996). Clinical efficacy trials using neutrophils from G-CSF-treated donors have yet to be conducted, but several small series suggest benefit, including benefit in patients with severe fungal infections where the chance of survival is otherwise extremely small (Taylor et al, 1996;Fleming et al, 1996;Leitman et al, 1996).…”

“…Are there long-term safety issues involved with the administration of one or several doses of G-CSF to normal persons? As yet there is no definitive answer to this question, but the risk of G-CSF administration is estimated to be very low (Bensinger et al, 1993;Caspar et al, 1995;Leitman et al, 1995;Liles et al, 1997;Nicola et al, 1983;Hammond et al, 1991;Chatta et al, 1994;Dale et al, 1996;Taylor et al, 1996). G-CSF is a natural cytokine, and elevations of endogenous G-CSF comparable to the levels obtained when rhG-CSF is used to mobilize and collect neutrophils occur with many types of infections Kawakami et al, 1990).…”