Tumor Lysis Syndrome (TLS)

Etiology/cancers most likely to cause TLS:
--Non-Hodgkin's lymphomas (Burkitt's, lymphoblastic, B-ALL>>DLBCL>>indolent NHL)
--ALL (WBC count >100,000 is highest risk)
--AML (WBC count >50,000 is highest risk)
--CLL (WBC count 10-100K when treated with fludarabine)

Pathophysiology: results from massive tumor cell lysis with release of potassium, phosphate, nucleic acids

• Metabolism of nucleic acids --> uric acid, which is poorly water soluble
• Due to high metabolic demands, phosphorus concentration in malignant cells is 4x that of normal cells
• Precipitation of uric acid and calcium phosphate in renal tubules leads to kidney injury
• Signs and symptoms: arrhythmia, renal failure, heart failure, tetany/cramping (from hypocalcemia), seizure

Diagnosis:
--Labaratory criteria (2 or more of the following):
     *uric acid >8 or 25 % increase from baseline
     *potassium >6 or 25% increase from baseline
     *phos>4.5 or 25% increase from baseline
     *Ca<& or 25% decrease from baseline
--clinical TLS is defined laboratory criteria + a creat >1.5x baseline, arrhythmia/sudden death, or seizure
--Cairo-Bishop score grades TL based on the creat elevation and clinical symptoms

Treatment:
--best treatment is early prevention (in our case the pt presented in TLS due to the highly aggressive nature of his cancer, but most commonly TLS is precipitated by starting chemotherapy/steroids
--IVF hydration is a mainstay of therapy
--allopurinol can be used prophylactically in pt's at low-int risk as it inhibits production of uric acid by inactivating xanthine oxidase, but does not degrade

---rasburicase (recombinant urate oxidase, an enzymes humans do not make endogenously) is used to treat severe hyperuricemia and is used preventitively in pt's at high risk of developing TLS.  The exzyme works by oxidizing uric acid into allantoin, which is water soluble--highly effective but $$
--hyperkalemia and hyperphosphatemia are treated with kayexelate and phosphate binders, but HD or CVVHD is often used in refractory cases
--caution of treating hypocalcemia before decreasing hyperphosphatemia as you can precipitate calcium phosphate precipitant formation-->stones and obstruction (unless life-threatening hypocalcemia)
--minimal data to support alkanization of the urine (theoretically to improve xanthine excretion)

(Christopher Woo MD, 12/14/10)

(Victoria Kelly MD, 6/11/10)