A review of the efficacy and tolerability of recombinant haematopoietic growth factors in bone marrow transplantation.
The clinical benefits of the haematopoietic growth factors (HGFs) granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in conjunction with bone marrow transplantation (BMT) have been established from numerous phase II/III clinical trials. Trials with filgrastim (recombinant G-CSF) have shown that it reduces the period of severe neutropenia by about one week, which leads to a reduction in infectious complications and earlier discharge from hospital. Similar clinical effects have been shown in placebo-controlled trials with recombinant GM-CSF. The effect of other HGFs on haematopoietic reconstitution has been investigated in animals and preliminary human studies, however, further data are required before their clinical efficacy can be determined. G-CSF is well tolerated in the BMT setting. GM-CSF also appears to be well tolerated at low doses, but increased toxicity may be seen at higher dosages. Clinical studies have also indicated that the HGFs do not stimulate the proliferation of leukaemic cells, furthermore, graft-versus-host disease (GVHD) is not enhanced by the use of growth factors. Pharmacological purging of the bone marrow may lead to a reduction in the granulocyte-macrophage colony-forming unit (CFU-GM) content of transplanted marrow. An alternative purging approach is the positive selection of CD34+ marrow stem cells. This technique may also be used to select stem cells from the peripheral blood for use in conjunction with or as an alternative to autologous or allogeneic BMT.
Barge
A J
AJ
Amgen Ltd, Cambridge, UK.
D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D000069585:Filgrastim; D005544:Forecasting; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D016298:Hematopoietic Cell Growth Factors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy; D009503:Neutropenia / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D003115:Colony-Stimulating Factors; D016298:Hematopoietic Cell Growth Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000069585:Filgrastim