Neutropenia Independently Associated With Poor Outcomes, but Not When Treated With G-CSF

Jaime Rosenberg

Despite a meaningful survival, neutropenia is independently associated with poor outcomes among critically ill patients with cancer, according to a new study. However, neutropenia was no longer significantly associated with outcome in patients treated with granulocyte colony-stimulating factor (G-CSF), suggesting a beneficial impact of the treatment.

Using public-domain databases, such as PubMed and the Cochrane database, researchers performed a meta-analysis of 114 articles focusing on critically ill patients with cancer from May 2005 to May 2015. Authors of 30 studies provided individual data on age, gender, year of admission, underlying malignancy, history of allogeneic stem cell transplantation, severity score, need for organ support, neutropenia during intensive care unit stay, neutropenia duration, use of G-CSF, follow-up, and outcome.

The dataset included 7515 patients, including 1702 patients with neutropenia. The majority of studies (27) had hospital mortality as the variable of outcome and 3 had 28-day mortality as the variable of outcome. The median age of patients was 60 years, 3366 (44.8%) had a solid tumor, and 439 were allogeneic stem cell transplant recipients (5.8%).

Among the patients, the unadjusted rate of mortality was 47.1%, with a mortality rate of 60.2% among patients with neutropenia and 43.2% among patients without neutropenia. After adjusting for confounders, the researchers observed that neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = .03).

When analyzed separately, admission period, underlying malignancy, nor need for mechanical ventilation impacted the influence of neutropenia on outcome. In patients admitted after 2007, neutropenia was independently associated with an increased risk of mortality (OR 1.40; 95% CI 1.16-1.70; P <.001). They also found that neutropenia was independently associated with increased mortality in patients with hematological malignancies (OR 1.30; 95% CI 1.11-1.51; P <.001).

However, the researchers did not see the same results when looking at the 788 patients treated with G-CSF, of which 587 were neutropenic. After adjusting for confounders, neutropenia was not independently associated with outcome (OR 1.03; 95% CI, 0.70-1.51; P = .90). According to the researchers, this finding suggests that the use of G-CSF may influence the prognostic impact of neutropenia in this setting.

“Prophylactic use of G-CSF in patients with hematological malignancy or solid tumors has proven efficacy in decreasing the risk or duration of neutropenia, in limiting the risk of infectious disease and in specific settings decreasing both overall mortality and infection-related mortality,” wrote the researchers. However, they added, “Conversely, use of G-CSF in patients with already overt infections was found to have a limited benefit in neutropenic patients.”

Georges Q, Azoulay E, Mokart D, et al. Influence of neutropenia on mortality of critically ill cancer patients: results of a meta-analysis on individual data [published online December 4, 2018]. Critical Care. doi: 10.1186/s13054-018-2076-z.
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