Table 1. Clinical decision rules examined.

	Patient and disease related factors	Episode specific factors	Rule formulation	Outcome	Inclusion criteria	Exclusion criteria
Klaassen [24]	None	Absolute monocyte count	Absolutely monocyte count >100/mm3 = low risk of bacteraemia	Significant bacterial infection	ANC <500cells/mm3 or ≤1000cells/mm3 and falling. Temperature >38.0°C ≥2 occasions in ≥12 h, or once >38.5°C, or localised infection	New malignant diagnosis; bone marrow or stem-cell transplantation in preceding 6 months. Another medical condition that independently required inpatient observation. Interstitial infiltrate or lobar consolidation on chest x-ray
Alexander [28]	AML, Burkitts lymphoma, induction ALL, progressive disease, relapsed with marrow involvement	Hypotension, tachypnea/hypoxia <94%, new CXR changes, altered mental status, severe mucositis, vomiting or abdominal pain, focal infection, other clinical reason for in-patient treatment	Absence of any risk factor = low risk of serious medical complication	Significant adverse outcome	ANC ≤500/mm3, temperature >38.5°C. Outpatient status.	Post stem cell transplant
Rondinelli [27]	2 points for central venous catheter, 1 point for age >5 years	4.5 points for clinical site of infection,2.5 points for no URTI, 1 point each for fever >38.5°C, hemoglobin ≤7 g/dL	Total score <6 = low risk of serious infectious complication	Serious infectious compllications	ANC <500cells/mm3 or ≤1000cells/mm3 and falling, temperature ≥37.8°C ≥3 occasions in ≥24 h, or once >38.0°C. First episode per patient (new or relapsed disease)	Second or subsequent episode. Episodes in progressive disease (<6 m from between completing therapy and relapse). History of BMT
PINDA [26]	Relapsed leukaemia, chemotherapy within 7 days of episode	CRP ≥90 mg/dL, hypotension, platelets ≤50 G/L	Zero risk factors or only low platelets or only <7 days from chemotherapy = low risk of invasive bacterial infection	Invasive bacterial infection	ANC ≤500cells/mm3, axillary temperature ≥38.0°C ≥2 occasions 1 h apart, or once ≥38.5°C	Not reported
Ammann [32]	Bone marrow involvement, central venous catheter, pre-B-cell leukemia	Absence of clinical signs of viral infection, CRP >50 mg/dL, white blood cell count <0.5 G/L, hemoglobin >10 g/dL	Three or fewer risk factors = low risk of significant infection	Significant infection	Age 1–18 y, episode following non-myleoablative chemotherapy, temperature >38.5°C or >38°C for >2 h, and ANC <500 cells/mm3	High dose chemotherapy
SPOG (Adverse events rule) [7]	Applied after 24 hours: 4 points for chemotherapy more intensive than ALL maintenance	Applied after 24 hours: 5 points for hemoglobin >90 g/L, 3 points each for white blood cell count <0.3 G/L, platelet <50 G/L, any adverse event occurred	Total score <9 = low risk of adverse FN outcome	Significant adverse outcome	Age 1–18 y, episode following non-myleoablative chemotherapy, temperature >38.5°C or >38°C for >2 h, and ANC <500 cells/mm3	High dose chemotherapy
SPOG (Bacteraemia rule) [18]	None	Applied after 24 hours: shaking chills ever observed, haemoglobin >90 g/L, platelet <50 G/L, any other need for IP treatment	No risk factors = low risk of bacteraemia presenting after 24 hours	Late bacteraemia (>24 h)	Age 1–18 y, episode following non-myleoablative chemotherapy, temperature >38.5°C or >38°C for >2 h, and ANC <500 cells/mm3	High dose chemotherapy
Hakim [16]	Score from cancer diagnosis: AML = 20, ALL/lymphoma = 7, Solids = 0	Clinical presentation of serious unwell or toxic = 14, fever at presentation: ≥39°C = 11, ANC <100/mm3 = 10 points	Total score <24 = low risk of serious infection or sepsis	Serious infection or sepsis	Outpatient, temperature >38.3°C or >38°C for >1 h, and ANC <500 cells/mm3	Inpatients, stem cell transplant recipients
Hakim [16]	Score from cancer diagnosis: AML = 11, others = 0. Relapsed disease = 11. Non-white patient = 8	Clinical presentation of serious unwell or toxic = 20	Total score <20 = low risk of any medical complication	Any medical complication	Outpatient, temperature >38.3°C or >38°C for >1 h, and ANC <500 cells/mm3	Inpatients, stem cell transplant recipients
Delebarre [14] (abstract only)	1 point for hematological malignancy, chemotherapy at high-risk of prolonged neutropenia,	1 point for clinical signs of local infection, fever >39°C, white cell count <500/mm3 or monocytes <100/mm3 and procalcitonin >0.3 ng/ml. TWO points for severe sepsis.	High risk >1 point.	Severe infection	Unclear	Unclear
Mian [15] (abstract only)		No clear rule – uses postive blood culture result and raised CRP	No clear rule	Intensive care admission	Unclear	Unclear
Badiei [17]		Platelets <20 g/dL, temperature ≥39°C, ANC <100/mm3, mucositis, abnormal CXR on presentation	Risk of infection greater with more risk factors: no single threshold applied	Life threatening infection	Outpatient, temperature >38.5°C or >38°C for >1 h, and ANC <500 cells/mm3	BMT, Fever with new diagnosis, inpatient status

AML = acute myeloid leukaemia; ANC = Absolute neutrophil count; BMT = bone marrow transplant; CXR = chest radiograph; CRP = C-reactive protein; PINDA = Programa Infantil Nacional de Drogas Antineoplásticas; SPOG = Swiss Pediatric Oncology Group; URTI = upper respiratory tract infection.