Key Points
- Patients undergoing cytotoxic chemotherapy and hematopoietic stem cell transplant are at risk for infection, particularly during the period of neutropenia.
- The risk of infection increases with the depth and duration of neutropenia, with the greatest risk occurring in patients who experience profound, prolonged neutropenia after chemotherapy, which is most likely to occur in the period prior to engraftment during hematopoietic cell transplantation and following induction chemotherapy for acute leukemia.
- Fever can be an important indicator and is often the only sign or symptom of infection although clinicians should also be mindful that severely or profoundly neutropenic patients may present with suspected infection in an afebrile state, or even hypothermic.
- Prevention and appropriate management of febrile neutropenia (FN) is important because the rate of major complications (e.g. hypotension, acute renal, respiratory or heart failure) in the context of FN is approximately 25–30%, and mortality up to 11%. In the setting of severe sepsis or septic shock the hospital mortality rate may be as high as 50%.
- Carmona-Bayonas A, Jimenez-Fonseca P, Virizuela Echaburu J, et al: Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study. J Clin Oncol 33:465-71, 2015.
- Kuderer NM, Dale DC, Crawford J, et al: Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258-66, 2006.
- Legrand M, Max A, Peigne V, et al: Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 40:43-9, 2012.
Antimicrobial Prophylaxis
- Risk of febrile neutropenia should be systematically assessed (in consultation with infectious disease specialists as needed), including patient-, cancer- and treatment-related factors (see Table 1). (Strong Recommendation; EB-B-I)
- Antibiotic prophylaxis with a fluoroquinolone is recommended for patients who are at high risk for febrile neutropenia or profound, protracted neutropenia (e.g. most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS), or hematopoietic stem cell transplantation (HSCT) treated with myeloablative conditioning regimens). Antibiotic prophylaxis is not routinely recommended for patients with solid tumors. (Moderate Recommendation; EB-B-H)
- Antifungal prophylaxis with an oral triazole or parenteral echinocandin is recommended for patients at risk for profound, protracted neutropenia, such as most patients with AML/MDS or HSCT. Antifungal prophylaxis is not routinely recommended for patients with solid tumors. Further distinctions between recommendations for invasive candidiasis and invasive mold infection are provided within the full text of the guideline. (Moderate Recommendation; EB-B-I)
- Prophylaxis is recommended, e.g. trimethoprim-sulfamethoxazole (TMP-SMX), for patients receiving chemotherapy regimens associated with >3.5% risk for pneumonia from Pneumocystis jirovecii (e.g. those with ≥20 mg prednisone equivalents daily for ≥1 month or those based on purine analogs). (Strong Recommendation; EB-B-H)
- Herpes simplex virus (HSV)-seropositive patients undergoing allogeneic HSCT or leukemia induction therapy should receive prophylaxis with a nucleoside analog (e.g. acyclovir). (Strong Recommendation; EB-B-H)
- Treatment with a nucleoside reverse transcriptase inhibitor (e.g. entecavir, tenofovir) is recommended for patients at high risk of Hepatitis B reactivation. (Moderate Recommendation; CB-B-I)
- Yearly influenza vaccination with inactivated vaccine is recommended for all patients receiving chemotherapy for malignancy and for all family and household contacts, and health care providers. (Moderate Recommendation; CB-B-I)
- The Expert Panel also supports other vaccination recommendations for immunosuppressed adult oncology patients that are contained within the IDSA guideline for vaccination of the immunosuppressed host. (Moderate Recommendation; CB-B-I)
Rubin LG, Levin MJ, Ljungman P, et al: 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 58:e44-100, 2014.
Additional recommended precautions:
- All health care workers should comply with hand hygiene and respiratory hygiene/cough etiquette guidelines to reduce the risk for aerosol- and direct or indirect contact-based transmission of pathogenic microorganisms in the healthcare setting. (Strong Recommendation; CB-B-I).
- Outpatients with neutropenia from cancer therapy should avoid prolonged contact with environments that have high concentrations of airborne fungal spores (e.g. construction and demolition sites, intensive exposure to soil through gardening or digging, household renovation). (Strong Recommendation; CB-B-I)
Table 1. Factors to Consider in Assessing Risk of a Febrile Neutropenic Episode in Patients Undergoing Cytotoxic Chemotherapy for Malignancy
| Factors Related to: | Factor | Effect on Risk | |
|---|---|---|---|
| Patient characteristics | Advanced age | Risk increases if ≥65 years | |
| Performance status | Risk increases if ECOG ≥2 | ||
| Nutritional status | Risk increases if albumin <35 g/L | ||
| Prior FN episode | Risk in cycles 2–6 is 4-fold greater if FN episode occurs in cycle 1 | ||
| Comorbidities | FN odds increase by 27%, 67%, and 125%, respectively, for 1, 2 or ≥3 comorbidities | ||
| Underlying malignancy | Cancer diagnosis | Diagnosis acute leukemia/MDS high-grade lymphoma soft tissue sarcoma NHL/myeloma germ cell carcinoma Hodgkin lymphoma ovarian carcinoma lung cancers colorectal cancers head & neck carcinoma breast cancer prostate cancer | Reported FN rates 85% to 95% 35% to 71% 27% (95% CI: 19–34.5%) 26% (95% CI: 22–29%) 23% (95% CI: 16.6–29%) 15% (95% CI: 6.6–24%) 12% (95% CI: 6.6–17.7%) 10% (95% CI: 9.8–10.7%) 5.5% (95% CI: 5.1–5.8%) 4.6% (95% CI: 1.0–8.2%) 4.4% (95% CI: 4.1–4.7%) 1% (95% CI: 0.9–1.1%) |
| Cancer stage | Risk increases for advanced stage (≥2) | ||
| Remission status | Risk increases if not in remission | ||
| Cancer treatment response |
| ||
| Treatment for malignancy | Cytotoxic regimen | Risk is higher with regimens that administer:
| |
| Dose intensity | Increased risk if >85% of scheduled doses are administered | ||
| Degree & duration of GI &/or oral mucositis | Risk is greatest if NCI mucositis grade is ≥3 (GI) or if peak score on OMAS is ≥2 | ||
| Degree & duration of cytopenias | Profound, protracted neutropenia:
| ||
Table 2. Summary of Recommendations for Antimicrobial Prophylaxis
| Type of prophylaxis | Population | Recommendations | Timing of prophylaxis |
|---|---|---|---|
| Antibacterial | Patients at high risk of febrile neutropenia (Table 1) or profound, protracted neutropenia | Fluoroquinolone prophylaxis is recommended. | During period of expected neutropenia. |
| Antifungal | Patients at high risk of febrile neutropenia (Table 1) or profound, protracted neutropenia Patients with graft versus host disease (GVHD) | Oral triazole or parenteral echinocandin prophylaxis is recommended; a mold-active triazole is recommended where the risk of invasive aspergillosis is >6%, such as in patients with AML/MDS, or during treatment of GVHD. | During period of expected neutropenia. |
| Patients receiving chemotherapy regimens associated with >3.5% risk for pneumonia from Pneumocystis jirovecii (e.g. those with ≥20 mg prednisone equivalents daily for ≥1 month or those based on purine analogs) | Prophylaxis is recommended | Post-myeloid reconstitution or engraftment after SCT, particularly in the setting of post-engraftment augmented immunosuppression (for the treatment of GVHD). | |
| Antiviral | HSV-seropositive patients undergoing HSCT or leukemia induction therapy | Antiviral prophylaxis with a nucleoside analog is recommended (e.g. acyclovir). | Until recovery of the white blood cell count or resolution of mucositis, whichever occurs later. Duration can be extended for persons with frequent recurrent HSV infections or those with GVHD or can be continued as VZV prophylaxis for up to one year. |
| Patients at substantial risk of reactivation of HBV infection | Treatment with a nucleoside reverse transcriptase inhibitor (e.g. entecavir, tenofovir) | See Updated ASCO HBV Provisional Clinical Opinion (Hwang et al. J Clin Oncol. 33:2212–2220, 2015) | |
| Any individuals treated with chemotherapy for malignancy and family and household contacts | Administration of inactivated influenza vaccine is recommended for household contacts and healthcare providers. |
| |
| Immunosuppressed adult oncology patients | The Expert Panel also supports other vaccination recommendations for immunosuppressed adult oncology patients that are contained within the IDSA guideline for vaccination of the immunosuppressed host. | Not applicable |