New ASCO Guideline on Neutropenia and Fever

Nick Mulcahy

January 16, 2013

The American Society of Clinical Oncology (ASCO) has bulked up its advice to clinicians about managing patients who undergo chemotherapy.

The organization has issued a new guideline on how and when to prevent infection in chemotherapy outpatients who are neutropenic but not febrile. It provides advice on identifying patients who have both neutropenia and fever but are at low risk for complications and can be treated at home.

ASCO previously issued advice on how to prevent neutropenia in chemotherapy patients, so the new guidance, published online January 14 in the Journal of Clinical Oncology, is a logical progression.

"The first clinical practice guideline...provided recommendations on the appropriate use of hematopoietic colony-stimulating factors to aid in the management of patients undergoing chemotherapy for cancer who were at risk for neutropenia. However, ASCO had not previously addressed other measures (such as prophylactic antimicrobial drugs or protective environments) to prevent infection in outpatients who are neutropenic," coauthor Christopher R. Flowers, MD, MS, wrote in an email to Medscape Medical News.

He is from the Emory School of Medicine in Atlanta, Georgia, and is cochair of the ASCO expert panel that drafted the guideline.

The new guideline recommends that physicians attempt to prevent infection in outpatients with "profound" neutropenia but no fever. It advises using antibacterial and antifungal prophylaxis if neutrophils are expected to remain below 100/uL for more than 7 days, and says that the preferable agent for antibacterial prophylaxis is an oral fluoroquinolone and for antifungal prophylaxis is an oral triazole. This is not appropriate if other factors increase risks for complications or mortality, the authors add.

Not recommended are interventions such as footwear exchange, protected environments, respiratory or surgical masks, neutropenic diet, or nutritional supplements; evidence of clinical benefits from these interventions is lacking, they note.

The guidance about using antimicrobial drugs to prevent potentially life-threatening infections in outpatients with neutropenia is well established, said expert Jennifer Malin, MD, PhD, from the University of California, Los Angeles and WellPoint, the managed care company headquartered in Indianapolis, Indiana.

"The antibacterial/antifungal recommendations for prophylaxis are not new and are consistent with previous guidelines," she explained.

The use of antibacterial and antifungal prophylaxis is very restricted, and is limited to outpatients with profound neutropenia, said Dr. Malin, who was asked by Medscape Medical News for comment and was not on the ASCO panel.

In the guideline, profound neutropenia is defined as an absolute neutrophil count below 100/uL (equivalent to less than 0.1 × 109/L).

"While it sounds complex, generally speaking, only regimens used in either the transplant setting or for patients with acute leukemia cause that degree of neutropenia," she wrote in an email to Medscape Medical News.

The new guidance "aims to identify a select group of patients who are most likely to benefit from the prescription of antibiotics before there are signs of fever or infection," Dr. Flowers noted. "It also aims to reduce the development of resistant strains of infection, which may reduce downstream harms to patients and may also reduce healthcare costs."

The antibacterial and antifungal prophylaxis recommended by ASCO is generally not indicated when colony-stimulating factor prophylaxis has already effectively reduced the depth and duration of neutropenia, Dr. Flowers and his coauthors point out.

Keeping Some Patients With Febrile Neutropenia at Home

The guideline calls for prompt initial treatment of febrile neutropenia. Patients with neutropenia who develop a fever should go to the hospital, outpatient clinic, or doctor's office immediately to receive initial antibacterial treatment.

However, a "priority" of the new guideline is to help clinicians identify patients with febrile neutropenia who do not need to be fully hospitalized, Dr. Flowers noted.

He and his coauthors explain that the "potential advantages of outpatient management include increased convenience for patients and their family members, reduced costs of care, and, particularly for those at risk of infection, decreased exposure to hospital-acquired infections, which often may be resistant to the antibiotics used most frequently."

The guideline calls for complication risk in patients with febrile neutropenia to be assessed with the MASCC scoring system or Talcott's rules. Using these systematic risk-assessment tools "is likely to be new for most doctors," said Dr. Flowers.

Patients who are at lowest risk for complications will have an MASCC score above 21 and fall into Talcott's group 4. Even low-risk patients sometimes have complications, so suitable candidates have to be "carefully selected" for home care, he said.

"Because medical complications occurred in up to 11% of patients identified as being at low risk for medical complications after an episode of fever during a period of neutropenia, inpatient treatment should remain the standard approach for managing patients," he explained.

Outpatient management of febrile neutropenia is appropriate only for patients who are able to comply with frequent clinic visits, who live within 1 hour or less than 30 miles from a hospital, who have a caretaker at home 24 hours a day, and who have 24-hour access to a telephone and transportation to get to the hospital.

Patients who experience a clinical worsening of their condition, organ dysfunction, or certain comorbid conditions should be managed in the hospital.

When febrile neutropenia is managed at home, the first treatment should be with oral antibacterial drugs (typically a fluoroquinolone antibiotic plus amoxicillin/clavulanate). Intravenous antibiotics are recommended for patients who are at high risk for complications and thus are given in the hospital.

ASCO Endorses International Pediatric Guideline

In pediatric news, ASCO announced this week that it is endorsing a guideline developed by the International Pediatric Fever and Neutropenia Guideline Panel (J Clin Oncol. 2012;30(35):4427-4438). This guideline provides recommendations related to the diagnosis, ongoing management, and initial antifungal and antibacterial treatment of febrile neutropenia in children with cancer and/or undergoing blood stem cell transplantation.

Febrile neutropenia is a common complication in children with cancer who receive chemotherapy, according to ASCO.

"This is the first comprehensive, evidence-based guideline to specifically address the management of febrile neutropenia in children with cancer," said Dr. Flowers in a press statement.

The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online January 14, 2013. Abstract