Tumor Lysis Syndrome Flashcards
Vincent
what is TLS
rapid lysis of cells leading to the release of massive quantities of intracellular components into the bloodstream
caused by cytotoxic tx or spontaneous lysis
subsequent catabolism can lead to emergent life threatening conditions
what are some dx lab values for TLS
Uric acid > 8 mg/dL
Phosphate > 4.5 mg/dL
Potassium > 6 mEq/L
Corrected calcium < 7 mg/dL
At least 2 criteria observed within a 24 hour period
what are some clinical dx factors of TLS
Meets criteria for AKI
Sx: cardiac dysrhythmia, seizure, neuromuscular irritability, HoTN, HF, sudden death, etc.
Lab dx + at least one of the clinical criteria listed above
what are some risk factors for TLS
New dx of advanced stage diffuse large B-cell lymphoma (DLBCL) w large retroperitoneal mass → aggressive hematologic malignancy w large tumor burden “bulky disease”
Older age/pre-existing renal dysfunction
Pre-existing LDH elevation
What is considered high risk for TLS
Hematologic malignancies (leukemias and lymphomas)
– Advanced stage (3-4)
–Bulky disease
– Acute leukemia w WBC > 100
– LDH > 2*ULN
Pre-existing renal dysfunction or oncologic renal involvement
Uric acid or electrolytes > ULN
what is considered intermediate risk for TLS
Solid tumors that are highly sensitive, advanced stage, or large tumor burden:
– Neuroblastoma, SC lung cancer**
Hematologic malignancies w lower WBC and LDH cut offs
– Not advanced stage or bulky
what is considered low risk for TLS
Most solid tumors except those that are highly chemo sensitive advanced stage or large tumor burden
CML
what is hyperuricemia
Purine nucleic acids are catabolized into hypoxanthine → kidneys unable to clear uric acid fast enough → uric acid crystallization and deposition in renal tubules → AKI or renal failure
Tx recommendations for hyperuricemia
Hydration (goal urine output: ~ 100 mL/hour)
Allopurinol or rasburicase
– Per FDA: Febuxostat limited to patients who cannot tolerate other agents due to an increased risk of AE (SJS, cardiac, all cause mortality)
Goal: normalize uric acid level
allopurinol is preferred for …
ppx agent for patients at risk of developing TLS
what is the MOA of allopurinol
blocks conversion of nucleic acids released from cancer cells: hypoxanthine to xanthine to uric acid
Does not remove existing uric acid
Allopurinol AE
pruritic rash, diarrhea, hypersensitivity skin reactions
HLA-B*5801 allele = increased risk of severe cutaneous AE
allopurinol dose
600 mg x1, then 300 mg daily
Start tx 1-2 days prior to chemotherapy and continue for at least 7-10 days or until signs of TLS are absent
Allopurinol special population
renal dose adjust in CKD
Allopurinol DDI
6-MP, azathioprine
what to monitor w allopurinol
repeat uric acid levels according to TLS protocol and renal function
rasburicase is preferred for …
Preferred agent for lab or clinical TLS tx. May also be used as ppx in high risk pts
Rasburicase MOA
decreases uric acid by converting it into inactive metabolite (allantoin), easily excreted in urine.
Does not inhibit formation of uric acid
Rasburicase dose
0.1-0.2 mg/kg/day for up to 7 days
*Single fixed dose
Uric acid < 12 mg/dL: 3 mg x 1
Uric acid > 12 mg/dL: 6 mg x 1
Monitor every 4-6 hours and readmin as necessary
Rasburicase AE
hypersensitivity (anaphylaxis), oxidative hemolytic anemia, methemoglobinemia
rasburicase special population
no renal adjustments
CI in G6PD deficiency
Rasburicase clinical pearls
Special lab: creates false uric acid serum results → blood sample must be collected and put on ice w assay performed within 4 hours
Immediate onset of action
$$
No concern utilizing allopurinol and rasburicase together
what is the most life threatening abnormality of TLS
hyperkalemia
hyperkalemia possible sx
cardiac conduction abnormalities, arrhythmia, widening of QRS, muscle weakness, sudden cardiac death, etc
what to monitor in hyperkalemia
EKG- continuous cardiac rhythm monitoring
classes of hyperkalemia
mild/mod: ≥ 5-6.5 mEq/L and asymptomatic
Severe: sx OR ≥ 6.5 mEq/L
tx for mild/moderate hyperkalemia
Acute shift:
IV insulin regular 0.1 U/kg x 1 or 10 U x 1:
Followed by 25-50 gram of dextrose 50%
Less common shifting agents: albuterol nebulizer, sodium bicarb IV
Elimination:
IV loop diuretics – quick onset
K binders – slow onset
Ex: lokelma, kayexalate, etc
tx for severe hyperkalemia
Same tx options as mild/moderate AND
IV calcium gluconate 1-2g over 2-5 minutes to stabilize the heart
Renal replacement therapy (RRT) if life threatening or refractory
what happens when there is high levels of phosphate
increased risk of calcium/phosphate precipitation
Precipitate builds up and injures renal tubules → worsening AKI or failure
Secondarily causes hypocalcemia
is tx of hyperphosphatemia necessary if mild and asymptomatic in TLS
no
Pharmacologic tx not indicated unless severe/sx
hyperphosphatemia tx
Preventative measures
Initiate low phosphate diet
Avoid phosphorus in fluids
Pharmacologic tx:
Non-calcium phosphate binders (sevelamer hydroxide, lanthanum carbonate, etc)
Renal replacement therapy (RRT)– indicated in sx or refractory cases
hypocalcemia sx
muscle cramps, tetany, seizures, arrhythmias
is tx of hypocalcemia necessary for those who are asymptomatic in TLS
Tx not recommended due to increased risk of precipitate formation w phosphorous
is tx of hypocalcemia necessary for those who are symptomatic or have severe hypocalcemia in TLS
yes
Tx at lowest effective dose
Calcium gluconate 50-100 mg/kg over 2-5 minutes
monitoring for hypocalcemia
EKG (continuous cardiac monitoring), corrected Ca or ionized Ca every 4-6 hours
AKI Tx
Hydration – IV NS
Goal urine output: ~100 mL/hr OR 3 L/day
Consider mild diuresis to achieve goal
Avoid LR due to phos/calcium + K
Tx the underlying problem: hyperuricemia, hyperphosphatemia, etc
Eliminate other possible nephrotoxic agents
May have to consider RRT in severe cases w volume overload or oliguria
when to consider Renal replacement therapy
severe/refractory hyperkalemia
severe/refractory hyperphosphatemia
Acidosis
Fluid overload unresponsive to diuretics
Uremia causing encephalopathy
when does TLS occur
within first 48-72 hours after cytotoxic therapy initiation
when can first lab signs of TLS be observed
within 6-24 hours after initiation
when can ppx tx be dc for TLS
7-10 days
what are exacerbating meds of TLS
Thiazides: increase uric acid
Lithium: increase uric acid
ACE/ARB: increase K and may worsen AKI
IV fluids w electrolyte additives: increase electrolyte supplements
Multivitamin: increase electrolyte supplement
Cholecalciferol: increase calcium and risk for calcium/phos precipitate
Nephrotoxic meds: NSAIDs, aminoglycosides, etc
what are the guideline directed preventative measures for hydration
PO/IV fluids starting at least 24 hours prior to start of start of tx
goal UO: 100 ml/hr or 3 L per day
not urinary alkalization anymore
what are the guideline directed preventative measures for urate lowering therapy
allopurinol or rasburicase
allopurinol is preferred ppx agent
what are the guideline directed preventative measures for vigilant lab and clinical monitoring**
Low risk: once daily
Intermediate: every 8-12 hours
High: every 4-6 hours
what are the guideline directed preventative measures for cytoreduction considerations
Case-to-case basis
Consider starting steroids or hydroxyurea to decrease tumor burden prior to tx initiation
