Clinical Benefits of GCSF

The dangers of neutropenia are manifold, whether that neutropenia is iatrogenic or congenital in nature since neutrophils play a critical role in protecting the body against

Table 3

Comparison of Filgrastim and Pegfilgrastim




No. of amino acids Cell source Glycosylation Pegylation C

Area under the curve

175 E. coli None No

1.65-0.80 ng/mL for single

75-^g/kg dose 5.5-1.8 for single 75-^g/kg dose 14.3-4.3 (0-24 h, ng [h/L]) for single 75-^g/kg dose

E. coli


43.6-20 ng/mL for single

30-^g/kg dose 9.50-3.51 for single 30-^g/kg dose 887-336 (0-infinity, ng [h/L]) for single 30-^g/kg dose micro-organisms. The most intuitively obvious application of rHuG-CSF would be when endogenous amounts are low—it would not, for instance, be predicted that an autoimmune neutropenia involving destruction of neutrophils might respond to rHuG-CSF. Among iatrogenic neutropenias, chemotherapy-induced neutropenia in patients with cancer is widely discussed and is the best documented. It is in this setting that the first study of rHuG-CSF was performed. In 1987, Bronchud et al. (12) completed a small study in patients with lung cancer who received rHuG-CSF on alternating cycles of therapy. They noted a reduction in the severity of neutropenia in those cycles in which rHuG-CSF was administered. Since that time a large number of studies in a wide variety of chemotherapy regimes and other diseases have been published. These include lung cancer, lymphoma, breast cancer, bone marrow transplantation, testicular cancer, AIDS-related malignancies, myelodysplastic disorders, acute leukemia, congenital and cyclic neutropenias, and aplastic anemia, all of which are reviewed in Mortsyn et al. (88).

Overall, the benefits of rHuG-CSF are that with its administration in chemotherapy-or radiotherapy-induced neutropenia, neutrophil recovery will begin sooner, proceed at a more rapid pace, and reduce the period when a patient might be in danger of developing febrile episodes. rHuG-CSF has few side effects, with bone pain being the only adverse effect of note, and it is normally managed with non-narcotic analgesics.

In addition to being used directly to increase neutrophil counts, rHuG-CSF can be used to mobilize precursor cells from the bone marrow to the blood, where they can be more easily collected. Although the mechanism of this effect remains largely unknown, by 1995 more than 80% of all transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) were performed with cells harvested from the blood rather than the bone marrow (89). These peripheral blood progenitor cells (PBPCs) have found use beyond the oncology setting, such as autoimmune disease (90).

Currently, stem cells harvested from the peripheral blood after rHuG-CSF treatment represent one of several sources of stem cells (more strictly progenitor cells) that form the basis of so-called cell therapy. Alternative sources of such stem cells include umbilical cord blood, adult bone marrow, fetal tissues, and embryonal stem cells. The debate over the capacity of the cells from each of these sources is an active one, as are the ethical issues surrounding the use of each. Recent work, however, has indicated that early claims of stem cell plasticity (the ability to be "plastic," or flexible, with regard to contribution to other tissues) are becoming more widely appreciated and exploited (91). Indeed, such is the level of excitement stemming from recent data indicating that PBPCs may be able to contribute to repair of the heart after myocardial infarction (92) that the entire August 2002 issue of the journal Experimental Hematology was dedicated to this question.

Additional uses for rHuG-CSF have been suggested, some supported by preliminary clinical data. Closure of fistulas in Crohn's disease has been reported (93,94), as has quicker resolution of ulcers on the feet of patients with diabetes (95).

In addition to these beneficial effects of rHuG-CSF, there have also been reports of side effects such as bone pain (96,97) and secondary leukemias. Leukemia evolving after rHuG-CSF in support of cancer therapy is a relatively rare event and may be associated with the exposure to mutagenic drugs such as topotecan. In other diseases, such as congenital neutropenias, it has been suggested that leukemia may be part of the normal evolution of the disease and that only the life-preserving effect of rHuG-CSF in early life allows the full expression later in life of the leukemic potential of some congenital neutropenias (98,99). In the same population, the development of osteoporosis with extended rHuG-CSF treatment has been reported, although it remains unclear whether this is related to rHuG-CSF use or to a natural progression of the disease that is only expressed when rHuG-CSF allows the patients to survive long enough to develop symptoms (100,101).

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