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American Society of Clinical Oncology Endorsement: Guideline for the Management of Fever and Neutropenia in Children with Cancer and or Undergoing Hematopoietic Stem Cell Transplantation


 

 Authors
Christopher R. Flowers, Eric J. Bow, Patricia M. Flynn, John M. Goldberg, Kieren A. Marr, Lisa Musser, Tom Oliver, Mark R. Somerfield, Beth A. White, and Roland A. Ammann

SUMMARY OF RECOMMENDATIONS

 

 

INITIAL PRESENTATION OF FN

Risk Stratification

Evaluation

Treatment

Adopt a validated risk stratification strategy and incorporate it into routine clinical management (1C).

Obtain blood cultures at onset of FN from all lumens of central venous catheters (1C).

 

Consider peripheral-blood culture concurrent with obtaining central venous catheter cultures (2C).

 

Consider urinalysis and urine culture in patients where  clean-catch, midstream specimen is readily available (2C).

 

Obtain chest radiography only in symptomatic patients (1B).

High-Risk FN

Use monotherapy with an antipseudomonal β-lactam or a carbapenem as empiric therapy in pediatric high-risk FN (1A).

 

Reserve addition of a second Gram-negative agent or  glycopeptide for patients who are clinically unstable, when a resistant infection is suspected, or for centers with a high rate of resistant pathogens (1B).

 

Low-Risk FN

In children with low-risk FN, consider initial or step-down outpatient management if the infrastructure is in place to ensure careful monitoring and follow-up (2B).

 

In children with low-risk FN, consider oral antibiotic administration if the child is able to tolerate this route of administration reliably (2B).

ONGOING MANAGEMENT OF FN: 24 to 72 hours or more after initiation of empiric antibacterial treatment

Modification of Treatment

Cessation of Treatment

In patients who are responding to initial empiric antibiotic therapy, discontinue double coverage for Gram-negative infection or empiric glycopeptide (if initiated) after 24 to 72 hours if there is no specific microbiologic indication to continue combination therapy (1B).

 

Do not modify the initial empiric antibacterial regimen based solely on persistent fever in children who are clinically stable (1C).

 

In children with persistent fever who become clinically unstable, escalate the initial empiric antibacterial regimen to include coverage for resistant Gram-negative, Gram-positive, and anaerobic bacteria (1C).

All Patients

Discontinue empiric antibiotics in patients who have negative blood cultures at 48 hours, who have been afebrile for at least 24 hours and who have evidence of marrow recovery (1C).

 

Low-Risk FN

Consider discontinuation of empiric antibiotics at 72 hours in low-risk patients who have negative blood cultures and who have been afebrile for at least 24 hours, irrespective of marrow recovery status, as long as careful follow-up is ensured (2B).

EMPIRIC ANTIFUNGAL TREATMENT: 96 hours or more after initiation of empiric antibacterial treatment

Risk Stratification

Evaluation

Treatment

Patients at IFD high-risk are those with AML or relapsed acute leukemia, those receiving highly myelosuppressive chemotherapy for other malignancies, and those undergoing allogeneic HCST with persistent fever despite prolonged (≥ 96 hours) broad-spectrum antibiotic therapy and expected prolonged neutropenia (>10 days); all others should be categorized as IFD low-risk (1B).

All Patients

Consider galactomannan in bronchoalveolar lavage and cerebrospinal fluid to support diagnosis of pulmonary or CNS aspergillosis (2C).

 

In children, do not use ß-D-glucan testing for clinical decisions until further pediatric evidence has accumulated (1C).

 

IFD High-Risk

Consider prospective monitoring of serum galactomannan twice per week in IFD high-risk hospitalized children for early diagnosis of invasive aspergillosis (2B).

 

In IFD high-risk children with persistent FN beyond 96 hours, perform evaluation for IFD; evaluation should include CT of the lungs and targeted imaging of other clinically suspected areas of infection (1B); consider CT of the sinuses in children ≥ 2 years of age (2C).

 

IFD Low-Risk

In IFD low-risk patients, do not implement routine galactomannan screening (1C).

All Patients

Use either caspofungin or liposomal amphotericin B for empiric antifungal therapy (1A).

 

IFD High-Risk

In neutropenic IFD high-risk children, initiate empiric antifungal treatment for persistent or recurrent fever of unclear etiology that is unresponsive to prolonged (≥ 96 hours) broad-spectrum antibacterial agents (1C).

 

IFD Low-Risk

In neutropenic IFD low-risk children, consider empiric antifungal therapy in the setting of persistent FN (2C).

*Parenthesis indicates GRADE strength of recommendation (1, strong; 2, weak) and quality of evidence (A, high; B, moderate; C, low or very low).

Abbreviations: AML,  acute myeloid leukemia; CT, computed tomography; FN, fever and neutropenia; GRADE, Grades of Recommendation Assessment, Development and Evaluation; CNS, central nervous system; HSCT, hematopoietic stem-cell transplant; IFD, invasive fungal disease

 

 

 

 

 

ASCO Guideline Disclaimer: The clinical practice guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. (“ASCO”) to assist practitioners in clinical decision making. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating physician, as the information does not account for individual variation among patients. Recommendations reflect high, moderate or low confidence that the recommendation reflects the net effect of a given course of action.  The use of words like “must,” “must not,” “should,” and “should not” indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating physician in the context of treating the individual patient. Use of the information is voluntary.  ASCO provides this information on an “as is” basis, and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.


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