Jordan King PharmD Candidate

Hyperuricemia Hyperkalemia Hyperphosphatemia Hypocalcemia

Kidney injury

Laboratory: >2 within 3 days before or 7 days after

Clinical: >1 + Laboratory Serum Creatinine Seizures Cardiac dysrhythmias Death

Hyperuricemia Hyperkalemia Hyperphosphatemia Hypocalcemia

Laboratory: >2 Simultaneously within 3 days before or 7 days after

Clinical: >1 + Laboratory

Hyperuricemia Hyperkalemia Hyperphosphatemia Hypocalcemia (symptomatic

hypocalcemia constitutes tumor lysis syndrome)

Serum Creatinine Seizures Cardiac dysrhythmias Death

25% change from baseline NOT considered criterion

Cancer Mass mass = lysed cells Large tumor burden

Organ infiltration, bone marrow involvement

Cell Lysis Potential LDH Cancers more susceptible to treatment Intensity of initial treatment

Patient Factors Pre-existing nephropathy Dehydration Hypotension Nephrotoxins (vancomycin, aminoglycosides, contrast die) Oliguria

Supportive Care Inadequate hydration Potassium or Phosphate supplementation Delayed uric acid removal (allopurinol vs rasburicase)

 IV Fluids
Increase renal perfusion, increase GFR, decrease acidosis, increase urine output

Loop diuretic
Increase urine output

 Rasburicase
Breaks down uric acid Prevents xanthine accumulation

Allopurinol
Does not breakdown uric acid (2 days to remove) Xanthine accumulation = xanthine nephropathy

 Plasma uric acid levels were measured immediately before uric acid-lowering agents and at 4 hrs, 12 hrs and every 12 hrs through 96 hrs Main objective was to compare the decrease in plasma uric acid levels by the 2 uric acid-lowering groups in the first 5 days of chemotherapy Primary efficacy endpoint was AUC0-96 of plasma uric acid curve

Outcome Measured Mean uric acid AUC0-96 Change from baseline (%) Time to uric acid control (< 8.0 mg/dL) in baseline hyperuricemia

Rasburicase

Allopurinol

Statistical Significance P < .0001

Rasburicase
128.1 mg/dL.hr 328.5 mg/dL.hr

-86.0

-12.1

P < .0001

4.0 hours

23.9 hours

 Hyperkalemia
Cardiac Dysrhythmias Most dangerous; sudden death Limit K+ intake during risk period Continuous cardiac monitoring Check K+ levels Q4-6hrs Oral SPS
Other: dialysis, glucose + insulin, Ca+ glucoronate

Hypocalemia
Cardiac Dysrhythmias Neuromuscular Irritability Limit Phosphorus intake during risk period Provide lowest dose Ca+ to relieve symptoms (symptomatic) Do NOT treat nonsymptomatic Phosphate binders

 Renal replacement therapy

Lower threshold to begin therapy in TLS Continuous replacement removes more phosphate Hyperphosphatemia-induced symptomatic hypocalcemia Hyperuricemia typically NOT an indication (rasburicase)

 8 year old boy presents to otolaryngologist for tonsillectomy. Two days after appointment parents took pt emergency department for congestion, sore throat and difficulty breathing. Dexamethasone 4mg was administered IM and loratadine prescribed. In next 36 hours the patients congestion and breathing improved, but malaise and vomiting developed. He returned to the emergency department where he was found to be dehydrated.

WBC: 84,000 mm3 Na: 133 mmol/L K: 5.9 mmol/L Bicarb: 16 mmol/L SCr: 1.0 mg/dL Phos: 8.5 mg/dL Ca: 6.7 mg/dL Uric acid: 12.3 mg/dL LDH: 4,233 IU/L

 Chest x-ray revealed a small mediastinal mass ECG was normal Suspicion for tumor lysis syndrome

2 boluses of NS (20 ml/kg) Rasburicase (0.15 mg/kg) Aluminum hydroxide 800 mg Maintenance IV fluids (2.5L/m2)

Transferred by ambulance to a tertiary care center and diagnose with T-cell ALL

 Complications
Oliguria Hyperphosphatemia SCr increased to 2.1 next day and peaked at 3.8 on day 5 HTN that resolved after 2 months

Pt did not require dialysis 5 years after diagnosis remains in remission

 Goldman SC, Holcenberg JS, Finklestein JZ, et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood. 2001 May 15;97(10):29983003. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med. 2011 May 12;364(19):1844-54.