1. Febrile Neutropenia Pedia Case

2. History AZ, 4 yo male from Bulacan admitted for the 3 rd 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

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

4. PE BP:100/60, PR:100, RR:30 (tachypneic), T= 38.5°C wt=15kg, ht=102cm Slightly pale palpebral conjunctivae Unremarkable neuro exam

5. Lab Results Day 1Day 3 Normal range Interpretation HGB 100100 115-155 anemic Hct 3837 35-45 normal Wbc 4000100004,500–11,000may indicate BM failure Lymp 804425-33 high; viral or chronic infection Seg 155654-62 neutropenia; normal Stab 53-5 normal Anc 80 5601,500-8,000 * *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).

6. Lab Results Normal urinalysis, chest xray BCS: Pseudomonas aeruginosa after 24 hrs incubation

7. Other Diagnostic Tests Initial laboratory evaluation includes a complete blood count 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

8. Medications Ceftazidime, Amikacin BCS after 3 days antibiotics showed no growth Discharged improved

9. Our patient presents with febrile neutropenia

10. 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

11. 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)

12. 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

13. 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

14. Adverse Reaction to Chemotherapy Rule in - Neutropenia - Weakness -Fever Rule out - Usually presents with abdominal distress and ulcerative stomatitis

15. Infectious Rule in - Fever - Tachypnea - Weakness - (+) BCS P. aeruginosa Rule out - Cannot be ruled out

16. Pathophysiology of Febrile Neutropenia in our patient

17. 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

18. 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

19. 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

20. 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.

21. 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

22. 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.

23. Management Cotrimoxazole – Especially for patients with ALL – Patient should receive this as prophylaxis against Pneomocyctic infection for the duration of chemotherapy