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Table 2 Clinical management recommendations for HD IL-2 therapy

From: High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014

Issue Considerations Management
Venous access Central line (for possible vasopressors) Typical
Double or triple lumen PICC line placement
Power inject and large volume capacity Remove temporary lines at end of cycle
Minimize catheter associated infection Variations
Broviac/Hickman catheter
Subclavian/IJ catheter
IV fluids Maintenance of volume with CLS Typical
Boluses for blood pressure support D5NS or D5LR 10 ml - 125 ml/hr
Administration of drugs PRN KCL, HCO3, Mg replacement
Replacement of electrolytes Variations
IL-2 only compatible with D5W D5W, NS, 0.45% NaCl
Infections No active infections Typical
Prevention Gram + prophylactic antibiotic
IV catheter likeliest source Variations
Avoid unnecessary in-dwelling catheters Expanded coverage per hospital
Chills/rigors Chills and rigors occur 1-2 hrs after IL-2 Fever-Typical
Fever Fever is common 2-4 hrs after IL-2 Acetaminophen 650 mg 30 min pre-dose, q 4-6 hrs and prn
Indomethacin 25 mg q 6-8 hrs
Constitutional symptoms Muscle joint aches continuous and progressive during IL-2 treatment Fever-Variation
Meperidine 25 mg IV q 15 m prn
Morphine 2-4 mg IV q 15 m prn
Nausea/vomiting Episodic occurrence throughout therapy Typical- Prophylaxis
Nausea > vomiting Ondansetron 0.15 mg/kg q 8 hrs
Granisetron 1 mg daily
Ondansetron at longer interval
Compazine 10 mg po q 6 hrs
Use of antinausea agents prn
Epigastric distress Gastritis induced by stress, medications Typical
H2 blocker prophylaxis
PPI prophylaxis
Mucositis/stomatitis Progressive with continued treatment Typical
No prophylaxis
Oncology mouthwash
Diarrhea Can be profuse and increases with therapy Typical
5HT-3 antagonist anti-emetic prophylaxis Imodium
may have positively impacted Lomotil
  Break between IL-2 doses
  5HT-3 antagonist prophylaxis
Patient monitoring I & O, Weight Per shift and daily
Blood pressure, pulse, respirations, temp Q 2-4 hrs
Blood work Daily
EKG Continuous cardiac monitoring
O2 Saturation Q 2-4 hrs
Mental status examination Q 8 hrs
Increase frequency as needed
Aldesleukin/Interleukin-2 dose and administration IL-2 incompatible with salt solutions. Typical: 600,000 IU/kg infused over 15 minutes Q 8 hrs up to 14 doses.
Dissolve in sterile water for injection Dilute into 50 cc D5W Variations: 720,000 IU/kg Q 8 hrs Q 12 hrs < 14 maximum doses
Stop infusion, flush IV tubing with 50 cc D5W before and after each dose.  
Hypotension Maintain systolic BP 80-90 mm hg Fluid boluses, 250-500 ml NS
Blood pressure nadirs 4-6 hrs after each dose with diminished recovery with cumulative dosing 2xday
Increase maintenance fluid rate
Phenylephrine 0.1-4.0 mcg/kg/min
Hold next dose
Prior to each dose anticipate ability to respond to next nadir DC IL-2
Dopamine 1-6 ug/kg/min
Progressive refractoriness to support measures Pressors with minimal fluids
Fluids without pressors
Cardiac arrhythmias Sinus tachycardia Manage BP and fever
Common and progresses over a cycle
Peaks 2-4 hrs after dose with fever and hypotension
Must resolve prior to next dose
Supraventricular tachycardia, atrial fibrillation Medical Conversion
Less common Cardizem as needed
Atrial fibrillation Digoxin
Ventricular tachycardia Medical Conversion
Acute treatment
Discontinue IL-2
Renal function   Typical
Oliguria Output less than 50-100 cc/8 hrs Fluid bolus, if no improvement next shift hold IL-2 dose
Rising creatinine Creatinine >3-4
Stop NSAIDS and nephrotoxic antiobiotics
Urine output and creatinine resolve after discontinuation of IL-2 Hold overnight dose
If am creatinine improved continue
If only one kidney always consider obstruction of ureter Variations
Dopamine 1-6 mcg/kg/min
Pulmonary Tachypnea/Dyspnea Typical
Diagnose etiology and treat Oxygen 2-4 L nasal cannula, increasing up to 35% rebreather
Hypoxic causes-Fluid overload, capillary leak, bronchospasm Reassurance or sedative for anxiety, treat bronchospasm or acidosis if appropriate
Non hypoxic causes Hold IL-2 dose if O2sat < 95%
Anxiety, fever, acidosis
Maintain O 2 sat > 92-5% Variation
Monitor bicarbonate
Peripheral edema Expect to gain 5-10% body weight Elevation, compression, limit fluid support in subsequent cycles
Treat edema symptomatically Diuretics upon conclusion of IL-2 dosing are not necessary but may speed process
Entrapment of peripheral nerves in upper extremity may need therapy Treat peripheral nerve pain
Neurotoxicity   Typical
Protean manifestations Formal neuro checks
Gradual onset with sudden worsening near end of cycle Enlist family evaluation
May persist after cessation of therapy Lorazepam and Haloperidol
Delusions, Visual hallucinations Hold IL-2 liberally for suspected neurotoxicity
Warn patient of vivid dreams after discharge
Dermatologic   Typical
Rash, erythema, dry desquamation Emollient lotions and creams Oatmeal bath
Pruritus Antihistamines
Moist dermatitis Hold IL-2 dose
Nonalcohol, no steroid topicals
Metabolic Hypomagnesemia, hypocalcemia (but low albumin - so corrected may be WNL), Hypokalemia- Daily electrolyte panels
Acidosis due to diarrhea, hypoperfusion Correct electrolytes cautiously prn
Hypothyroidism a slow onset problem Magnesium and HCO3, particularly if diarrhea a problem
HCO3 < 18 meq/L hold dose of IL-2
Check TSH at beginning of cycle
RL as support fluids may decrease need for HCO3
Hepatic ↑Bilirubin (up to 10) Monitor daily
↓Albumin (down to 1.8) No intervention except if SGOT SGPT are >5x
↑Hepatic aminotransferases Resolves spontaneously
  Stop acetaminophen if bilirubin > 5
Hematologic ↓Platelets Transfuse platelets if < 20 K
Lymphs ↓during IL-2, ↑post therapy Other abnormalities require no intervention
Eosinophils progressively ↑with several cycles Significant anemia needs evaluation for cause
Endocrine Hypothyroidism - slow onset after completion of treatment Check TFTs at beginning of cycle and monitor TFTs with subsequent visits
Requires serial monitoring