Febrile Neutropenia

Pedia Case

History

• AZ, 4 yo male from Bulacan admitted for the 3rd time

• CC: fever for 3 days• HPI: - Diagnosed w/ ALL since 3 yo- Has gone through 3 cycles of chemotherapy,

most recent of which was last week

History

- 3 days PTA: low to moderate grade fever (max 38.5°C) after 3rd cycle of chemotherapy, given paracetamol to no avail. Symptoms persisted w/ dec. appetite and weakness

ROS:(+) weakness(+) cough(+) soft stool

PE

• BP:100/60, PR:100, RR:30 (tachypneic), T= 38.5°C

• wt=15kg, ht=102cm • Slightly pale palpebral conjunctivae• Unremarkable neuro exam

Lab Results

Day 1 Day 3 Normal range Interpretation• HGB 100 100 115-155 anemic• Hct 38 37 35-45 normal• Wbc 4000 10000 4,500–11,000 may indicate BM failure• Lymp 80 44 25-33 high; viral or chronic infection• Seg 15 56 54-62 neutropenia; normal• Stab 5 3-5 normal• Anc 80 560 1,500-8,000 *

*in practical clinical terms, a normal ANC is 1.5 or higher; a "safe" ANC is 500-1500; a low ANC is less than 500. A safe ANC means that the patient's activities do not need to be restricted (on the basis of the ANC).

Lab Results

• Normal urinalysis, chest xray• BCS: Pseudomonas aeruginosa after 24 hrs

incubation

Other Diagnostic Tests

• Initial laboratory evaluation includes a complete bloodcount with differential and platelets count, liver and renal function tests, oxygen saturation, urinalysis

• cultures of other suspected sites • tissue sampling of suspected sites (bronchoalveolar lavage,

lumbar puncture, etc).• Serology and PCR to determine presence of infectious

organisms

Medications

• Ceftazidime, Amikacin• BCS after 3 days antibiotics showed no growth• Discharged improved

Our patient presents with febrile neutropenia

Febrile Neutropenia• A clinical presentation of fever ( one temperature

reading > or = 38.5 C or 3 readings of > 38C but < or = to 38.5C per hour) in a neutropenic or granulocytopenic patient

• Neutropenia- absolute neutrophil count of < 1000 cells/mm3 and can be associated with high risk of developing severe bacterial and fungal infections when absolute neutrophil count of < 500 cells/mm3)

• Granulocytopenia- <500/cumm or falling counts near this level starting from 1000/cu.mm

Causes of Febrile Neutropenia• Immunodeficiency ( Malignancy, malnutrition)• Infections (75% of children with Febrile

Neutropenia has documented site of infection)-Gram (+) cocci are the most common as well

as P.aeruginosa, E. coli, and Klebsiella-Gram (-) pathogens-Enterobacter and Acinetobacter

• Malignancy (the cancer itself and/or the immunosuppressive drugs treatment for it)

Febrile Neutropenia in a patient w/ ALL can be:• Non-infectious- Due to the malignant process itself- Due to adverse reactions to chemotherapeutic

agents• Infectious

Acute Lymphocytic Leukemia (malignant process itself)

• Rule in- Patient history- Fever (due to release of

endogenous pyogens)- Loss of appetite- granulocytopenia

• Rule out- unlikely to be the sole

cause of the symptoms because if fever is due to endogenous pyrogens, it is usually present at the time the tumor is diagnosed and the occurrence of fever at a later date should therefore be considered infectious until proven otherwise

Adverse Reaction to Chemotherapy

• Rule in- Neutropenia- Weakness- Fever

• Rule out- Usually presents with

abdominal distress and ulcerative stomatitis

Infectious

• Rule in- Fever- Tachypnea- Weakness- (+) BCS P. aeruginosa

• Rule out- Cannot be ruled out

Pathophysiology of Febrile Neutropenia in our patient

Etiology for Acute Lymphoblastic Leukemia(ALL) is still being studied but studies show that exposure to

insecticides and fertilizers in adults contribute to its development. It is also the most common leukemia in

children

AZ has been diagnosed with Acute Lymphoblastic Leukemia (malignancy) involving the bone marrow and

has underwent 3 cycles of chemotherapy (immunosuppressive)

AZ becomes immunodeficient and acquired INFECTION (Pseudomonas)

AZ developed Severe Febrile Neutropenia

Management

• Initial evaluation– PE (skin lesions, mucous membranes, IV catheter

sites, perirectal area)– Granulocyte count– Blood cultures, XRAY and other appropriate tests

based on Hx

Management

• Antibiotics– Use antibiotics active for both gram (-) and gram (+)

bacteria– It is important to note that risk stratification is very

important in the initial management of febrile neutropenia in the pediatric cancer setting to identify those at risk for of complications and mortality

– One goal of risk stratification has been to identify the low-risk patient who may be able to receive oral antibiotic therapy for febrile neutropenia

Management

• Antifungal therapy– Fungal infections in cancer patients are often

associated with neutropenia– Use a broad spectrum antifungal agent (ex.

Voriconazole and Posaconazole) but always keep in mind that azoles are different from each other and there is no singale antifungal efficacious against all fungi.

Management

• Antiviral therapy– Among the viral infections cancer patients are

prone to acquire, thise caused by the herpes group are prominent.

– Acyclovir has a long history of safety both as a therapeutic and prophylactic agent although a number of other drugs offer advantage.

– Drugs that offer activity against influenza virus are good options

Management

• G-CSF (Granulocyte-Colony Stimulating Factor)– Enhance granulocyte recovery after

chemotherapy– May have adverse affects such as fever,

hypoxemia and pleural effusion– Not a standard of care, yet.

Management

• Cotrimoxazole– Especially for patients with ALL– Patient should receive this as prophylaxis against

Pneomocyctic infection for the duration of chemotherapy