Three Decades of Progress in Treating Febrile Neutropenia

Treatment of febrile neutropenia (FN) has dramatically improved over the past three decades, but there is room for improvement, according to Jean Klastersky, MD, Institut Jules Bordet, Brussels, Belgium, who spoke at the Multinational Association of Supportive Care in Cancer (MASCC) / International Symposium on Supportive Care in Cancer, which took place in June 28 to 30 in New York City.

 

At the symposium, Klastersky reviewed progress over the past 30 years. “The past decades have witnessed advances in treating FN, most notably prevention of FN with use of granulocyte colony-stimulating factors [G-CSF]. Compared with 30 years ago, mortality and morbidity have declined and therapies are now simpler, less toxic, and more appropriately delineated according to patient risk status. Despite this progress, numerous challenges remain in high-risk patients. Further study is needed to define the optimal use of G-CSF in this group of patients,” Klastersky told listeners. 

 

In 1962, complications of febrile neutropenia were fatal for many patients. Today the rate of complications is 10% to 20%, and mortality is about 5%, he said. “Even though these rates seem low, they represent a large number of patients treated with chemotherapy who develop FN. We still lose a lot of patients, some of them young.”

 

Complications of FN can include hypotension, respiratory failure, ICU admission, and confusion. In addition, FN is expensive to treat: The mean cost of treating one episode is $7,700 for outpatients and $15, 231 for inpatients. Thus, treating on an outpatient basis reduces the cost-per-episode by 50%.

 

The MASCC scoring index for FN, developed in 2000, is now an accepted tool in clinical practice. The scoring index encompasses total symptom burden and individual symptoms. A MASCC score index of 21 or higher predicts a 5% risk of complications, which is considered low risk. These patients can be effectively treated with oral antibiotics, which reduce the cost of management compared with G-CSF, which is typically used in higher-risk patients.

 

Prerequisites for oral antimicrobial therapy for patients who develop FN include low risk according to MASCC scoring index, feasibility of oral antibiotics, and 24-hour observation period in the hospital. Klastersky emphasized the importance of 24 hours of observation prior to discharge.

 

Mortality and morbidity rates are higher in patients with MASCC scores <15 (poor risk) versus those with a score of 21 or higher. The rate of mortality due to gram-negative bacteremia is 43% in the higher-risk patients.

 

“Several studies have confirmed that low MASCC score [ie, <15] predicts for severe sepsis. We need protocolized approaches for these patients. Many of them are kept too long in the emergency department without antibiotics for several hours. They probably need more aggressive treatment,” he said.

 

The use of G-CSF to prevent FN is an important advance that can reduce the rate of FN by about 50% and also has an impact on mortality, he said. Both long-acting and short-acting G-CSF formulations are available. The choice depends on physician preference.

 

An algorithm for use of G-CSF has been developed, but it is based on economic considerations, not on clinical science, because G-CSF is expensive, Klastersky said. At first, G-CSF was given to a wider pool of patients, is now typically used in patients with higher risk. Further study is needed to establish whether the criteria for G-CSF prophylaxis should be expanded from those at relatively high risk to include lower-risk patients, Klastersky said. 

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