12.3 Oncologic Emergencies: Tumor Lysis Syndrome & Supportive Care

Board Certified Pediatric Pharmacy Specialist BCPPS

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1 Chapter 1: Pediatric Patient Characteristics — Growth, Anthropometrics & Perinatal Exposure

1.1 Normal Growth, Development & Growth-Chart Interpretation 1.2 Anthropometrics: Body Surface Area, Dosing Weights & Maximum-Dose Caps 1.3 Medication Use in Pregnancy and Lactation

2 Chapter 2: Developmental Pharmacokinetics & Neonatal Principles

2.1 Developmental PK: Absorption, Distribution & Body Water Dynamics 2.2 Hepatic Metabolism & CYP/UGT Isoenzyme Maturation 2.3 Renal Function Maturation & Glomerular Filtration Development

3 Chapter 3: Neonatal Critical Care & Prematurity Complications

3.1 Neonatal Sepsis & Meningitis (Early-Onset vs Late-Onset Sepsis) 3.2 Respiratory Distress Syndrome, Surfactant & Bronchopulmonary Dysplasia 3.3 Patent Ductus Arteriosus, Apnea of Prematurity & Necrotizing Enterocolitis

4 Chapter 4: Pediatric Infectious Diseases — Respiratory & ENT Infections

4.1 Acute Otitis Media, Sinusitis & Pharyngitis 4.2 Pediatric Community-Acquired Pneumonia & Parapneumonic Effusion 4.3 Bronchiolitis, RSV Prevention (Nirsevimab, Clesrovimab, Palivizumab) & Viral Lower Respiratory Infections

5 Chapter 5: Pediatric Infectious Diseases — Systemic, Bone & CNS Infections

5.1 Pediatric Meningitis, Encephalitis & Brain Abscess 5.2 Skin, Soft Tissue, Osteomyelitis & Septic Arthritis 5.3 Pediatric Sepsis, Febrile Neutropenia & Central Line-Associated Bloodstream Infections

6 Chapter 6: Pediatric Pulmonary Medicine — Asthma & Status Asthmaticus

6.1 Chronic Pediatric Asthma Assessment & Stepwise Outpatient Pharmacotherapy 6.2 Status Asthmaticus & Acute Exacerbation Pharmacotherapy in ED/PICU 6.3 Aerosol Drug Delivery, Spacers & Specialized Inhalation Devices

7 Chapter 7: Cystic Fibrosis & Chronic Pediatric Respiratory Disorders

7.1 Pathophysiology, Diagnosis & Airway Clearance in Cystic Fibrosis 7.2 CFTR Modulator Therapies & Monitoring 7.3 CF Pulmonary Exacerbations, Chronic Infection Management & Comorbidities

8 Chapter 8: Pediatric Cardiology & Hemodynamics

8.1 Congenital Heart Defects & Ductal-Dependent Lesions 8.2 Pediatric Heart Failure & Cardiomyopathies 8.3 Pediatric Arrhythmias & Syncope Management

9 Chapter 9: Pediatric Resuscitation, Shock & Critical Care Support

9.1 PALS Resuscitation Algorithms & Cardiac Arrest Pharmacotherapy 9.2 Pediatric Shock States & Vasoactive / Inotropic Selection 9.3 Extracorporeal Membrane Oxygenation (ECMO) & Critical Care PK

10 Chapter 10: Pediatric Neurology & Psychiatric Disorders

10.1 Neonatal Seizures & Pediatric Status Epilepticus 10.2 Pediatric Epilepsy Syndromes & Maintenance Anticonvulsants 10.3 Attention-Deficit/Hyperactivity Disorder (ADHD) & Pediatric Mood Disorders

11 Chapter 11: Pediatric Endocrinology & Metabolic Disorders

11.1 Pediatric Type 1 Diabetes Mellitus Management & Insulin Technologies 11.2 Diabetic Ketoacidosis (DKA) Protocols & Cerebral Edema Prevention 11.3 Growth Hormone, Pubertal Disorders & Congenital Adrenal Hyperplasia

12 Chapter 12: Pediatric Hematology, Oncology & Supportive Care

12.1 Sickle Cell Disease: Vaso-occlusive Crises & Disease-Modifying Therapies 12.2 Pediatric Acute Lymphoblastic Leukemia (ALL) & Chemotherapy Toxicities 12.3 Oncologic Emergencies: Tumor Lysis Syndrome & Supportive Care

13 Chapter 13: Pediatric Medication Safety & Error Prevention

13.1 High-Alert Pediatric Medications & Ten-Fold Dosing Calculation Traps 13.2 Smart Infusion Pumps & Dose Error Reduction Systems (DERS) 13.3 Medication Reconciliation & Pediatric Care Transitions

14 Chapter 14: Pediatric Compounding & Formulation Technology

14.1 Non-Sterile Compounding (USP <795>) & Liquid Formulations 14.2 Sterile Compounding (USP <797>) & Micro-Dosing Considerations 14.3 Hazardous Drug Handling (USP <800>) & Excipient Toxicities

15 Chapter 15: Fluids, Electrolytes & Clinical Nutrition Support

15.1 Fluid Requirements, Dehydration Assessment & Maintenance Therapy 15.2 Electrolyte Disturbances: Sodium, Potassium & Calcium Management 15.3 Pediatric & Neonatal Parenteral Nutrition (PN) Formulation

16 Chapter 16: Pediatric Pain Management, Sedation & Delirium

16.1 Age-Specific Pain Assessment Tools & Analgesic Selection 16.2 Procedural Sedation & Rapid Sequence Intubation in Children 16.3 PICU Delirium, Iatrogenic Withdrawal & Weaning Strategies

17 Chapter 17: Biostatistics & Study Design in Pediatric Research

17.1 Observational vs Experimental Pediatric Study Designs 17.2 Biostatistical Testing, Power & Sample Size in Small Pediatric Cohorts 17.3 Diagnostic Testing, Sensitivity, Specificity & Predictive Values

18 Chapter 18: Pediatric Evidence Appraisal, Regulatory Framework & Ethics

18.1 Pediatric Drug Legislation: BPCA, PREA & Labeling Nuances 18.2 Institutional Review Boards (IRB), Assent & Informed Consent in Minors 18.3 Evaluating Clinical Practice Guidelines & Formulating Off-Label Recommendations

19 Chapter 19: Pediatric Education, Health Literacy & Communication

19.1 Caregiver Health Literacy & Pediatric Medication Adherence 19.2 Interprofessional Education & Clinical Teaching Strategies 19.3 Developing Age-Appropriate Patient Educational Materials

20 Chapter 20: Pediatric Immunizations & Public Health Advocacy

20.1 ACIP Pediatric Immunization Schedule: Routine Childhood Vaccines 20.2 Adolescent Immunizations, Vaccine Hesitancy & Catch-Up Schedules 20.3 Pediatric Public Health Disparities & Special Population Advocacy

21 Chapter 21: Pediatric Practice Management — Laboratory Stewardship, Pharmacoeconomics & Informatics

21.1 Pediatric Laboratory Practices: Blood Conservation, Sampling Timing & Age-Specific Reference Intervals 21.2 Pharmacoeconomics, Formulary Management & Cost-Containment in Pediatrics 21.3 Clinical Informatics, CPOE Decision Support & Drug Shortage Management

12.3 Oncologic Emergencies: Tumor Lysis Syndrome & Supportive Care

Key Takeaways Explain This Topic AI

The Cairo-Bishop definition establishes Laboratory Tumor Lysis Syndrome (LTLS) when two or more of the following criteria occur within 3 days prior to or 7 days after starting chemotherapy: hyperuricemia (>8.0 mg/dL or 25% increase), hyperkalemia (>6.0 mmol/L or 25% increase), hyperphosphatemia (>6.5 mg/dL in children or 25% increase), and hypocalcemia (<7.0 mg/dL or 25% decrease); Clinical TLS requires LTLS plus renal failure, cardiac arrhythmia, or seizures.

Prophylactic hyperhydration (2,000–3,000 mL/m2/day or 200 mL/kg/day targeting urine output ≥100 mL/m2/hr or ≥2–4 mL/kg/hr) must be administered without added potassium or calcium; urine alkalinization is strictly contraindicated in the setting of hyperphosphatemia because alkaline pH (≥7.0) promotes fatal calcium phosphate crystal precipitation in renal tubules.

Allopurinol (300–400 mg/m2/day divided TID) inhibits xanthine oxidase to block new uric acid formation, whereas rasburicase (0.1–0.2 mg/kg IV or a flat 3–6 mg single dose) directly degrades pre-existing uric acid into soluble allantoin within 4 hours; rasburicase is strictly contraindicated in G6PD deficiency due to the risk of life-threatening methemoglobinemia and severe hemolysis.

Blood samples drawn to monitor uric acid in patients who have received rasburicase must be collected in pre-chilled heparinized tubes, immediately immersed in an ice-water slurry, and analyzed within 4 hours to prevent in vitro enzymatic degradation and false undetectable uric acid reporting.

Pediatric febrile neutropenia (single temp ≥38.3°C or sustained ≥38.0°C for 1 hour with ANC <500/mcL) mandates empiric IV antipseudomonal monotherapy (cefepime 50 mg/kg q8h max 2 g, piperacillin-tazobactam, or meropenem) within a 60-minute 'door-to-needle' window, while routine PCP prophylaxis consists of oral TMP-SMX (5 mg/kg/day TMP divided BID 2–3 days per week).

Last updated: September 2026

12.3 Oncologic Emergencies: Tumor Lysis Syndrome & Supportive Care

Oncologic emergencies in pediatric hematology and oncology arise directly from tumor mass effects or from the rapid, massive lysis of malignant cells following initiation of cytotoxic chemotherapy. The sudden release of intracellular electrolytes, nucleic acids, and cellular metabolites overwhelms homeostatic clearance mechanisms, producing profound metabolic derangements, multiorgan failure, and early mortality.

Tumor Lysis Syndrome (TLS): Pathophysiology & Risk Factors

Tumor lysis syndrome (TLS) is characterized by the rapid breakdown of malignant cells that release large quantities of potassium, phosphorus, and nucleic acids into the systemic circulation:

Potassium: The primary intracellular cation (intracellular concentration ~140–150 mmol/L). Massive release overwhelms renal excretory capacity, producing life-threatening hyperkalemia within hours.

Phosphorus: Malignant lymphoblasts contain up to four times more intracellular organic phosphorus than normal mature lymphocytes. Rapid cell death dumps massive inorganic phosphate loads into plasma (hyperphosphatemia), which complexes with circulating calcium to precipitate insoluble calcium phosphate ( C a 3 ( P O 4 ) 2 Ca_3(PO_4)_2 C a 3 ​ ( P O 4 ​ ) 2 ​ ) crystals into renal collecting tubules and microvasculature, inducing acute nephrocalcinosis and secondary hypocalcemia .

Purine Nucleic Acids: Catabolized sequentially into hypoxanthine, then to xanthine, and finally to uric acid by the hepatic enzyme xanthine oxidase. Uric acid has low water solubility at normal physiological urinary pH ( p K a ≈ 5.4 – 5.7 pK_a \approx 5.4\text{--}5.7 p K a ​ ≈ 5.4 – 5.7 ). When filtered in massive amounts, it precipitates as needle-shaped monosodium urate crystals within the acidic lumen of the distal tubules and collecting ducts, producing obstructive uropathy, inflammation, and oliguric acute kidney injury. Purine Catabolic Cascade & Drug Interventions in TLS:

• Purine Nucleic Acids (Adenine, Guanine)
• │
• ▼
• Hypoxanthine
• │
• │ ◄── [Allopurinol Inhibits Xanthine Oxidase]
• ▼
• Xanthine
• │
• │ ◄── [Allopurinol Inhibits Xanthine Oxidase]
• ▼
• Uric Acid (Poor Aqueous Solubility; Precipitates in Renal Tubules)
• │
• │ ◄── [Rasburicase Catalyzes Degradation]
• ▼
• Allantoin + Hydrogen Peroxide (H2O2) + CO2
• (5–10x More Soluble in Water; Easily Excreted in Urine)
• Malignancy Risk Stratification

High Risk: Burkitt lymphoma/leukemia, lymphoblastic lymphoma, T-cell ALL, B-cell ALL with hyperleukocytosis ( W B C ≥ 100 , 000 / mcL WBC \ge 100,000/\text{mcL} W BC ≥ 100 , 000/ mcL ), AML with W B C ≥ 50 , 000 / mcL WBC \ge 50,000/\text{mcL} W BC ≥ 50 , 000/ mcL , and bulky tumors with baseline serum lactate dehydrogenase (LDH) > 2 × >2\times > 2 × upper limit of normal.

Intermediate Risk: B-ALL with WBC 50,000 to 100,000/mcL, AML with WBC 10,000 to 50,000/mcL, early-stage Burkitt lymphoma, and high-grade solid tumors (e.g., metastatic neuroblastoma, rhabdomyosarcoma) with extensive metastasis.

Low Risk: Indolent lymphomas, low-grade leukemias, and non-metastatic solid tumors.

Diagnostic Classification: Cairo-Bishop Definition

The standardized Cairo-Bishop Definition divides TLS into Laboratory TLS (LTLS) and Clinical TLS (CTLS) . Criteria must manifest within 3 days prior to or up to 7 days after the initiation of antineoplastic chemotherapy.

1. Laboratory TLS (LTLS)

Diagnosis requires two or more of the following metabolic abnormalities occurring concurrently within the 3-day pre-chemo to 7-day post-chemo window:

Metabolic Parameter Cairo-Bishop Diagnostic Threshold Percentage Change from Baseline

Hyperuricemia Uric Acid > 8.0 mg/dL > 8.0\text{ mg/dL} > 8.0 mg/dL ( > 476 mcmol/L >476\text{ mcmol/L} > 476 mcmol/L ) in children OR 25 % 25\% 25% increase from patient baseline

Hyperkalemia Potassium > 6.0 mmol/L > 6.0\text{ mmol/L} > 6.0 mmol/L ( > 6.0 mEq/L >6.0\text{ mEq/L} > 6.0 mEq/L ) OR 25 % 25\% 25% increase from patient baseline

Hyperphosphatemia Phosphorus > 6.5 mg/dL > 6.5\text{ mg/dL} > 6.5 mg/dL ( > 2.1 mmol/L >2.1\text{ mmol/L} > 2.1 mmol/L ) in children OR 25 % 25\% 25% increase from patient baseline

Hypocalcemia Corrected Calcium < 7.0 mg/dL < 7.0\text{ mg/dL} < 7.0 mg/dL ( < 1.75 mmol/L <1.75\text{ mmol/L} < 1.75 mmol/L ) OR Ionized Calcium < 1.12 mmol/L < 1.12\text{ mmol/L} < 1.12 mmol/L OR 25 % 25\% 25% decrease from patient baseline

2. Clinical TLS (CTLS)

Diagnosis requires the presence of Laboratory TLS (LTLS) PLUS at least one of the following clinical toxicities not attributable to other causes:

Renal Dysfunction: Serum creatinine ≥ 1.5 × \ge 1.5\times ≥ 1.5 × upper limit of normal for age , or oliguria ( < 0.5 mL/kg/hour <0.5\text{ mL/kg/hour} < 0.5 mL/kg/hour for ≥ 6 \ge 6 ≥ 6 hours).

Cardiac Arrhythmias: Life-threatening ventricular arrhythmias, heart block, or sudden cardiac arrest secondary to severe hyperkalemia or hypocalcemia.

Neuromuscular Seizures: Tetany, severe neuromuscular irritability, carpopedal spasm, altered mental status, or generalized tonic-clonic seizures secondary to severe hypocalcemia.

TLS Prevention & Management Protocols Management Algorithm for Tumor Lysis Syndrome:

• [High-Risk Pediatric Malignancy Identified]
• │
• ▼
• Aggressive Intravenous Hyperhydration (2,000–3,000 mL/m2/day without added K+/Ca2+)
• Target Urine Output: ≥100 mL/m2/hr (≥2–4 mL/kg/hr in infants <10 kg)
• │
• ┌─────────────────────┴─────────────────────┐
• ▼ ▼
• [Hyperphosphatemia Present?] [G6PD Deficiency Screen]
• NO Urinary Alkalinization • Negative: Rasburicase 0.1–0.2 mg/kg
• Alkaline pH (≥7.0) precipitates (Degrades existing uric acid)
• Calcium Phosphate (Ca x P > 60) • Positive: Allopurinol 300–400 mg/m2/day
• Nephrocalcinosis & Renal Failure (Avoid Rasburicase -> Hemolysis/MetHb)
• 1. Aggressive Intravenous Hyperhydration

Fluid Volume: Administer 2,000 to 3,000 mL/m 2 ^2 2 /day (or 150 to 200 mL/kg/day for infants < 10 kg <10\text{ kg} < 10 kg ), roughly 1.5 1.5 1.5 to 2 2 2 times maintenance.

Fluid Composition: D 5 D_5 D 5 ​ 0.2% NaCl or D 5 D_5 D 5 ​ 0.45% NaCl. STRICTLY EXCLUDE all potassium, calcium, and phosphate from intravenous hydration fluids.

Urine Output Benchmark: Target a continuous urine output of ≥ 100 mL/m 2 / hour \ge 100\text{ mL/m}^2/\text{hour} ≥ 100 mL/m 2 / hour (or ≥ 2.0 to 4.0 mL/kg/hour \ge 2.0\text{ to } 4.0\text{ mL/kg/hour} ≥ 2.0 to 4.0 mL/kg/hour in infants and young children). If urine output is inadequate despite adequate intravascular volume repletion, administer a loop diuretic ( furosemide 0.5 to 1.0 mg/kg IV ) to promote tubular flow, provided obstructive uropathy and hypovolemia are ruled out.

2. The Urinary Alkalinization Controversy: Why It Is Contraindicated

Historically, intravenous sodium bicarbonate was added to hydration fluids to alkalinize urine ( p H ≥ 7.0 – 7.5 pH \ge 7.0\text{--}7.5 p H ≥ 7.0 – 7.5 ), increasing the solubility of free uric acid. However, contemporary pediatric oncology guidelines strongly advise against urinary alkalinization , particularly when hyperphosphatemia is present, for several reasons:

Calcium Phosphate Precipitation: In an alkaline milieu ( p H ≥ 7.0 pH \ge 7.0 p H ≥ 7.0 ), phosphate ionizes into dibasic phosphate ( H P O 4 2 − HPO_4^{2-} H P O 4 2 − ​ ), which binds circulating calcium with high affinity. When the calcium-phosphorus solubility product exceeds 60 mg 2 / dL 2 60\text{ mg}^2/\text{dL}^2 60 mg 2 / dL 2 ( [ Calcium ] × [ Phosphate ] > 60 [\text{Calcium}] \times [\text{Phosphate}] > 60 [ Calcium ] × [ Phosphate ] > 60 ), calcium phosphate precipitates into renal tubules, myocardium, and cardiac conduction tissue, accelerating acute renal failure and causing fatal arrhythmias.

Exacerbation of Hypocalcemic Symptoms: Alkalinization increases the negative charge on serum albumin, promoting competitive binding of ionized calcium to albumin. This sharply reduces the physiologically active ionized calcium fraction , precipitating severe tetany, laryngospasm, and seizures.

Xanthine Precipitation: In patients receiving allopurinol, urinary alkalinization actually decreases the solubility of xanthine and hypoxanthine, promoting xanthine nephropathy.

Rasburicase Superiority: The availability of rasburicase rapidly clears uric acid without requiring an alkaline urine pH.

Caution

BCPPS Board Rule: Do NOT add sodium bicarbonate to hydration fluids in patients with hyperphosphatemia or those receiving rasburicase. Maintain neutral urine pH with aggressive hydration alone.

3. Hypouricemic Pharmacotherapy: Allopurinol vs. Rasburicase

Pharmacological Parameter Allopurinol (Zyloprim) Rasburicase (Elitek, Fasturtec)

Mechanism of Action Competitive inhibitor of xanthine oxidase ; blocks conversion of hypoxanthine → \rightarrow → xanthine → \rightarrow → uric acid Recombinant urate oxidase enzyme; directly catabolizes insoluble uric acid into highly soluble allantoin

Onset of Action Slow; requires 24 to 72 hours to reduce circulating uric acid levels Ultra-rapid; reduces plasma uric acid by > 95 % >95\% > 95% within 4 hours

Effect on Pre-existing Uric Acid ZERO effect ; prevents new uric acid synthesis but cannot degrade pre-existing circulating crystals Directly degrades and clears pre-existing circulating and tissue uric acid deposits

Pediatric Dosing 300 to 400 mg/m 2 ^2 2 /day orally divided TID (or 10 mg/kg/day divided TID; maximum 600–800 mg/day) 0.10 to 0.20 mg/kg IV infused over 30 minutes daily (or single flat-dose: 3 mg or 6 mg IV)

Primary Metabolic Risk Accumulation of insoluble hypoxanthine and xanthine → \rightarrow → xanthine nephropathy Generates hydrogen peroxide ( H 2 O 2 H_2O_2 H 2 ​ O 2 ​ ) → \rightarrow → severe methemoglobinemia and hemolysis in G6PD deficiency

Major Contraindications Severe hypersensitivity (HLA-B*58:01 allele; Stevens-Johnson syndrome / TEN) Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency

Rasburicase Black Box Warnings & Laboratory Sample Handling

G6PD Deficiency Black Box Warning: Rasburicase oxidizes uric acid to allantoin, generating stoichiometric quantities of hydrogen peroxide ( H 2 O 2 H_2O_2 H 2 ​ O 2 ​ ) . In erythrocytes with normal glucose-6-phosphate dehydrogenase (G6PD) activity, H 2 O 2 H_2O_2 H 2 ​ O 2 ​ is neutralized by reduced glutathione (GSH) generated via NADPH. In patients with inherited G6PD deficiency, erythrocytes cannot produce NADPH; unbuffered H 2 O 2 H_2O_2 H 2 ​ O 2 ​ oxidizes hemoglobin iron ( F e 2 + → F e 3 + Fe^{2+} \rightarrow Fe^{3+} F e 2 + → F e 3 + ), producing life-threatening methemoglobinemia and inducing massive oxidative membrane damage that precipitates acute intravascular hemolysis. Screen high-risk ethnic groups (African, Mediterranean, Middle Eastern, Southeast Asian descent) prior to administration when feasible. If severe hemolysis or methemoglobinemia occurs, discontinue rasburicase immediately and administer supportive care. Note that methylene blue is ineffective for rasburicase-induced methemoglobinemia in G6PD-deficient patients because its mechanism depends on NADPH generated by G6PD; use ascorbic acid or exchange transfusion instead.

Critical Laboratory Handling Mandate: Rasburicase remains enzymatically active ex vivo in drawn blood samples at room temperature. If blood is allowed to sit at room temperature, rasburicase will continue to rapidly degrade all uric acid in the tube, resulting in falsely low or undetectable laboratory uric acid measurements that mask severe in vivo hyperuricemia.

Important

Blood Sample Handling for Uric Acid in Rasburicase-Treated Patients:

Draw blood into pre-chilled heparinized tubes (green-top tubes placed on ice before venipuncture).

Immediately immerse the tube in an ice-water slurry (wet ice) .

Transport on ice directly to the clinical laboratory.

Centrifuge and assay the plasma within 4 hours of collection.

4. Management of Life-Threatening Hyperkalemia & Hyperphosphatemia

Acute Hyperkalemia ( K + > 6.0 – 6.5 mmol/L K^+ > 6.0\text{--}6.5\text{ mmol/L} K + > 6.0 – 6.5 mmol/L or ECG Changes):

Myocardial Membrane Stabilization: Calcium gluconate 10% at 50 to 100 mg/kg IV (0.5 to 1.0 mL/kg) infused over 5 to 10 minutes with continuous cardiac monitoring. Restores normal myocardial membrane threshold potential to prevent ventricular fibrillation. Does NOT lower serum potassium.

Intracellular Potassium Shifting:

Regular Insulin: 0.1 units/kg IV combined with Dextrose 25% 2.0 mL/kg IV (0.5 g/kg) over 30 minutes.

Nebulized Albuterol: 2.5 mg (weight < 20 kg <20\text{ kg} < 20 kg ) or 5.0 mg (weight ≥ 20 kg \ge 20\text{ kg} ≥ 20 kg ) via nebulizer over 15 minutes.

Sodium Bicarbonate: 1 to 2 mEq/kg IV over 10 minutes if metabolic acidosis is present.

Potassium Removal: Loop diuretics (furosemide 1 mg/kg IV); potassium-binding resins ( Sodium Zirconium Cyclosilicate [Lokelma] 5–10 g orally TID or Patiromer); emergent Continuous Renal Replacement Therapy (CRRT) or Hemodialysis if medical therapy fails.

Hyperphosphatemia ( > 6.5 mg/dL >6.5\text{ mg/dL} > 6.5 mg/dL ) & Hypocalcemia Management:

Treat hyperphosphatemia with hyperhydration and non-calcium oral phosphate binders ( Sevelamer carbonate 50–100 mg/kg/dose orally TID with meals).

Hypocalcemia Warning: Do NOT treat asymptomatic hypocalcemia! Administering intravenous calcium in a patient with severe hyperphosphatemia sharply increases the [ Calcium ] × [ Phosphate ] [\text{Calcium}] \times [\text{Phosphate}] [ Calcium ] × [ Phosphate ] product, precipitating widespread metastatic calcification in renal tubules, coronary vessels, and lung parenchyma. Administer IV calcium gluconate ONLY for symptomatic hypocalcemia manifested by tetany, seizures, or severe QTc prolongation.

Pediatric Febrile Neutropenia (FN)

Febrile neutropenia is a medical emergency that carries high mortality in pediatric oncology due to impaired inflammatory responses and rapid progression to septic shock.

Clinical Definitions:

Fever: A single oral or tympanic temperature measurement of ≥ 38.3 ∘ C \ge 38.3^\circ\text{C} ≥ 38. 3 ∘ C ( 101.0 ∘ F 101.0^\circ\text{F} 101. 0 ∘ F ) , OR a sustained temperature of ≥ 38.0 ∘ C \ge 38.0^\circ\text{C} ≥ 38. 0 ∘ C ( 100.4 ∘ F 100.4^\circ\text{F} 100. 4 ∘ F ) over a 1-hour duration.

Neutropenia: An Absolute Neutrophil Count (ANC) < 500 / mcL < 500/\text{mcL} < 500/ mcL , OR an ANC < 1 , 000 / mcL < 1,000/\text{mcL} < 1 , 000/ mcL with an anticipated decline to < 500 / mcL < 500/\text{mcL} < 500/ mcL within 48 hours. ANC Calculation (cells/mcL) = Total WBC (cells/mcL) × ( % Segmented Neutrophils + % Band Neutrophils 100 ) \text{ANC Calculation (cells/mcL)} = \text{Total WBC (cells/mcL)} \times \left( \frac{\%\text{ Segmented Neutrophils} + \%\text{ Band Neutrophils}}{100} \right) ANC Calculation (cells/mcL) = Total WBC (cells/mcL) × ( 100 % Segmented Neutrophils + % Band Neutrophils ​ )

The 60-Minute "Door-to-Needle" Benchmark: Broad-spectrum intravenous antimicrobials must be administered within 60 minutes of triage arrival .

First-Line Empiric Antimicrobial Monotherapy:

Cefepime: 50 mg/kg IV every 8 hours (maximum single dose 2,000 mg).

Piperacillin-Tazobactam: 80 to 100 mg/kg (piperacillin component) IV every 6 to 8 hours (maximum 4,000 mg/dose).

Meropenem: 20 mg/kg IV every 8 hours (maximum 1,000 mg/dose; preferred for penicillin anaphylaxis or ESBL history).

When to Add Vancomycin (15 mg/kg IV every 6 to 8 hours): Do NOT routinely add empiric vancomycin to initial monotherapy. Vancomycin is reserved for:

• Hemodynamic instability or septic shock
• Suspected central catheter-associated bloodstream infection (erythema, purulence at exit site)
• Clinically obvious skin or soft tissue infection
• Known colonization with Methicillin-Resistant S. aureus (MRSA)
• Severe mucositis in patients receiving high-dose cytarabine
• Supportive Care Prophylaxis Regimens
• 1. Pneumocystis jirovecii Pneumonia (PCP / PJP) Prophylaxis

Prolonged T-cell suppression and high-dose corticosteroid therapy place pediatric leukemia and lymphoma patients at extreme risk for life-threatening interstitial pneumonia caused by Pneumocystis jirovecii .

First-Line Regimen: Trimethoprim-Sulfamethoxazole (TMP-SMX): Dosed at 5 mg/kg/day (based on the trimethoprim component) orally divided twice daily , administered on 2 or 3 consecutive days per week (e.g., Monday-Tuesday-Wednesday or Friday-Saturday-Sunday).

Alternative Regimens (for Severe Sulfa Allergy / Documented G6PD Deficiency):

Dapsone: 2 mg/kg/day orally once daily (maximum 100 mg/day) OR 4 mg/kg once weekly (maximum 200 mg/week). Must screen for G6PD deficiency prior to initiation due to hemolytic risk.

Atovaquone (Mepron): Dosed at 30 to 45 mg/kg orally once daily with a high-fat meal (dosing: 30 mg/kg/day for ages 1–3 months and > 24 >24 > 24 months; 45 mg/kg/day for ages 4–24 months; maximum 1,500 mg/day).

Aerosolized Pentamidine: 300 mg once monthly via Respirgard II nebulizer for cooperative children ≥ 5 \ge 5 ≥ 5 years of age .

2. Chemotherapy-Induced Nausea & Vomiting (CINV)

Pediatric guidelines from the Pediatric Oncology Group of Ontario (POGO) and ASCO/MASCC stratify CINV regimens based on the emetogenic potential of the chemotherapy protocol:

Highly Emetogenic Chemotherapy (HEC) (e.g., cisplatin, cyclophosphamide ≥ 1 , 000 mg/m 2 \ge 1,000\text{ mg/m}^2 ≥ 1 , 000 mg/m 2 , high-dose cytarabine, dacarbazine): Requires an aggressive 3-Drug Prophylactic Regimen administered prior to antineoplastic infusion:

5-HT3 Receptor Antagonist: Ondansetron 0.15 mg/kg IV every 8 hours (maximum 16 mg/dose) OR Granisetron 10 to 40 mcg/kg IV once daily (maximum 1,000 mcg/dose).

Dexamethasone: 2 to 4 mg/m 2 ^2 2 orally or IV every 12 hours (Note: Omit dexamethasone if the chemotherapy protocol already incorporates therapeutic corticosteroids, as in ALL induction).

Neurokinin-1 (NK1) Receptor Antagonist:

Aprepitant (Oral): Approved down to 6 months of age; weight-tiered dosing for patients ≥ 6 \ge 6 ≥ 6 months: Body weight < 30 kg <30\text{ kg} < 30 kg : Day 1: 3.0 mg/kg (max 125 mg); Days 2 and 3: 2.0 mg/kg (max 80 mg); Body weight ≥ 30 kg \ge 30\text{ kg} ≥ 30 kg : Day 1: 125 mg ; Days 2 and 3: 80 mg .

Fosaprepitant (IV Prodrug): 4.0 mg/kg IV (maximum 150 mg) infused over 30 minutes as a single dose on Day 1.

Practice Pearls & BCPPS Exam Traps

Exam Trap 1: Never administer rasburicase to a patient with known or suspected G6PD deficiency. The resulting hydrogen peroxide surge triggers irreversible methemoglobinemia and massive intravascular hemolysis that cannot be treated with methylene blue.

Exam Trap 2: Do not interpret a post-rasburicase uric acid level of < 0.5 mg/dL <0.5\text{ mg/dL} < 0.5 mg/dL as therapeutic success if the blood specimen was left sitting on the nursing station counter at room temperature. The report reflects ex vivo destruction of uric acid in the tube rather than true intravascular status.

Exam Trap 3: Never add sodium bicarbonate to IV hydration fluids when serum phosphorus is elevated. Alkalinizing the urine in the face of hyperphosphatemia precipitates catastrophic calcium phosphate crystal nephropathy ( C a × P > 60 Ca \times P > 60 C a × P > 60 ), directly causing oliguric renal failure.

Board Rule: For pediatric febrile neutropenia, never delay the first dose of broad-spectrum antibiotics to await blood culture results, central line placement, or chest radiographs. The institutional "door-to-needle" time must be under 60 minutes .