Neutropenia colony-stimulating factors

Neutropenia is a drop in the number of circulating leukocytes, especially neutrophils. It can be induced by a variety of drugs. Treatment with cytotoxic antineo-plastic drags usually results in severe neutropenia, which can be treated with colony-stimulating factors (G-CSF, GM-CSF). 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

Lyman GH, Kuderer NM. The economics of the colony-stimulating factors in the prevention and treatment of febrile neutropenia. Crit Rev Oncol Hematol 2004 50 129-146. 

Esser, M. and Brunner, H. 2003. Economic evaluations of granulocyte colony stimulating factor in the prevention and treatment of chemotherapy-induced neutropenia. Pharmacoeconomics 21(18), 1295-1313. 

Heuser, M. and Ganser, A. 2005. Colony stimulating factors in the management of neutropenia and its complications. Annals of Hematology 84(11), 697-708. 

There has been a great deal of interest in the use of colony-stimulating factors to treat MDS. GM-CSF and G-CSF, which have been used in clinical trials, offer a potential dual benefit. Firstly, they can affect neutrophil development in the bone marrow, and so can improve the neutropenia that is associated with these disorders. Secondly, they have the potential to increase or repair the function of circulating neutrophils. Indeed, there are some reports to indicate that these CSFs can result in enhanced function of peripheral blood neutrophils in these patients. Most patients show improvements in neutrophil counts after GM-CSF or G-CSF administration. In some cases, this has been associated with a decrease in the number of infective episodes. 

Crawford J, Ozer H, Stoller R et al. Reduction by granuloc34e colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N EnglJMed 1991 325 164 170. 

Gabrilove JL, Jakubowski A, Scher H, et al. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med 1988 318 1414-1422. 

Neupogen (Amgen) Colony stimulating factor (treatment of neutropenia) 1.2... 

The administration of recombinant granulocyte colony-stimulating factor (G-CSF, filgrastim) can correct neutropenia and reduce infectious morbidity in infected patients with a variety of causes of severe neutropenia. Granulocyte macrophage colony-stimulating factor (GM-CSF, sar-gramostim) has also been used successfully in neutropenic patients. 

After a meticulous review of the biomedical literature, the panel concluded that routine use of colony-stimulating factors for primary prophylaxis of febrile neutropenia in previously untreated patients is not justified by existing data. There is evidence, however, that colony-stimulation factor administration can decrease the probability of febrile neutropenia in subsequent cycles of chemotherapy after a documented occurrence in an earlier cycle. However, dose reduction after a severe episode, rather than administration of colony-stimulating factors, should be considered as a primary therapeutic option. In the absence of clinical evidence or other compelling reasons to maintain chemotherapy dose intensity, physicians should consider chemotherapy dose reduction... 

F. Role in therapy According to Micro-medex, treatment of severe chemotherapy-related thrombocytopenia is hmited to platelet transfusions. There is a need for an alternative, especially due to the frequent use of myeloid colony-stimulating factors (G-CSF, GM-CSF) to reduce febrile neutropenia although effective, their use increases the risk of acute and prolonged thrombocytopenia, and the need for platelet transfusions. Other cytokines, such as interleukin-1 and interleukin-6, have been investigated as a means of ameliorating chemotherapy-induced thrombocytopenia, but results have been equivocal. 

Granulocyte colony-stimulating factor (G-CSF filgrastim) Neutropenia Cancer patients treated with myelosuppressive cancer chemotherapy... 

Granulocyte-macrophage colony-stimulating factor (GM-CSF sargramostim) Patients with severe chronic neutropenia... 

Bhana N Granulocyte colony-stimulating factors in the management of chemotherapy-induced neutropenia Evidence based review. Curr Opin Oncol 2007 19 328. [PMID 17545795]... 

Kaczmarski RS, Pazniak A, Lakhani A, Harvey E, Mufti GJ. 1993. A pilot study of low-dose recombinant human granulocyte-macrophage colony-stimulating factor in chronic neutropenia. Br J Hematol. 84 338-340. 

Effects of G-CSF (color) or placebo (black line) on absolute neutrophil count (ANC) after cytotoxic chemotherapy for lung cancer. Doses of chemotherapeutic drugs were administered on days 1 and 3. G-CSF or placebo injections were started on day 4 and continued daily through day 12 or 16. The first peak in ANC reflects the recruitment of mature cells by G-CSF. The second peak reflects a marked increase in new neutrophil production by the bone marrow under stimulation by G-CSF. Treated patients in this study had fewer days of neutropenia, days of antibiotic treatment, and days of hospitalization. They also had a lower incidence of infections. (Normal ANC is 2.2-8.6 x 109/L.) (Modified and reproduced, with permission, from Crawford et al Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991 325 164.)... 

Dale D. Current management of chemotherapy-induced neutropenia the role of colony-stimulating factors. Semin. Oncol. 2003 30 3—9. 

Kearns CM,Wang WC, State N, Ihle JN, Evans WE. Disposition of recombinant human granulocyte colony-stimulating factor in children with severe chronic neutropenia./. Pediatr. 1993 323 471-479. 

---