more on risks associated with G-CSF and GM-CSF which support White blood cells wchemo

[Lani]

Benefits may still outweigh risks, but risks deserve consider :

Growth Factors Commonly Given With Chemotherapy Associated With Increased Risk of Blood Diseases [Journal of the National Cancer Institute; Subscribe; Sample]
Women with breast cancer who receive compounds that stimulate white blood cell production to help their bodies better tolerate chemotherapy are at an increased risk of developing a type of leukemia or a condition called myelodysplastic syndrome, according to a new study in the February 7 Journal of the National Cancer Institute. The authors note that the absolute risk of the conditions is very small, but that risk should still be taken into consideration when making treatment decisions.

The growth factors granulocyte or granulocyte-macrophage colony-stimulating factor (G-CSF or GM-CSF) have been used to reduce the risk of infections from neutropenia, an abnormally low count of a certain type of white blood cell that helps control infections. Chemotherapy destroys these cells, and it is difficult for the body to quickly replace them.

However, there is some concern that these growth factors may keep cells alive that have been mutated by chemotherapy. Ordinarily, certain cell processes would recognize such damage and instruct the cell to die, but growth factors may save the mutant cell, allowing it to develop into a cancer called acute myelocytic leukemia (AML). There's also concern about the risk of a disease called myelodysplastic syndrome (MDS), in which the bone marrow—which produces blood cells—does not function normally. Indeed, some studies have hinted that cancer patients who receive growth factors with chemotherapy may have an increased risk of these two diseases.

Dawn Hershman, M.D., of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and New York Presbyterian Hospital, and colleagues set out to determine the association between G-CSF or GM-CSF use and the risk of AML or MDS among women treated with chemotherapy for early-stage breast cancer. Using a database that links cancer registry data from the Surveillance, Epidemiology, and End Results: (SEER) program with data from Medicare, the researchers identified 5,510 women age 65 and older who were diagnosed with breast cancer and treated with chemotherapy between 1991 and 1999. A total of 906 (16%) were treated with at least one course of G-CSF (832), GM-CSF (29), or both (49). Among these 906 patients, 16 (1.77%) developed AML or MDS; among the 4,604 women who didn't get growth factor treatment, 48 (1.04%) developed one of the diseases. The authors calculated that women who received GM-CSF or G-CSF had twice the risk of developing AML or MDS as women not treated with the growth factors.

"Our study demonstrates that the elevated risk of AML or MDS associated with adjuvant chemotherapy may be further increased by the concurrent use of growth factors," the authors write. "It is unclear if the growth factors cause an increased risk or if the requirements for their use cause an increased risk; however, the absolute overall risk appeared to be small, even among the elderly patients we studied. Nevertheless, if further research confirms this finding, this risk should be factored into clinical decisions with regard to the use of growth factors."

In an editorial, Ivo P. Touw, Ph.D., and Marijke Bontenbal, of the Erasmus University Medical Center Rotterdam in the Netherlands, review the possible biologic mechanisms for the increased risk, and point out that growth factor use has increased in recent years. They also note that the benefits of adjuvant chemotherapy for breast cancer may far outweigh any risk of a second cancer. "In clinical practice, ... the benefits of adjuvant chemotherapy are of a different order of magnitude than the risk of secondary MDS or AML," they write. "Furthermore, given all the unknown factors, associations could be found that have no causal relationship. The evidence for a potential role of G-CSF in the onset of AML/MDS, derived from only a few retrospective studies, thus has to be qualified as hypothesis generating rather than conclusive."


ABSTRACT: Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy [Journal of the National Cancer Institute]
Background: Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G-CSFs) or granulocyte-macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients.

Methods: Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stages I-III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided.

Results: Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15).

Conclusions: The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free.