tumor lysis syndrome. chikwa.Darlin.pptx

Tumor lysis syndrome

1. TUMOUR LYSIS SYNDROME Darlington Chikwa (CUZ)

2. Definition A potentially life-threatening oncologic emergency resulting from the rapid destruction of tumor cells, which leads to hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia, which can result in end-organ damage.

3. Epidemiology The exact incidence is undetermined, but retrospective studies show up to 42% in high-grade non-Hodgkin lymphoma.
Common in hematologic cancers (e.g., non-Hodgkin lymphoma 30%, acute myeloid leukemia 19%, acute lymphoblastic leukemia 13%), with laboratory TLS at 9-19% and clinical TLS at 5-7% in various studies.
Rare in solid tumors but reported in cases like lung cancer (NSCLC 8 cases, SCLC 13 cases), breast (13 cases), gastrointestinal (39 cases), and others, often in advanced or metastatic stages.

4. Classification It is classified into laboratory TLS (biochemical abnormalities without clinical symptoms) and clinical TLS (when complications like acute renal failure, seizures, or cardiac arrhythmias occur). Also classified by risk: high (>5% incidence, e.g., advanced Burkitt lymphoma), intermediate (1-5%), low (<1%), based on tumor type, WBC count, and LDH levels.

5. Etiology TLS most commonly occurs after initiating cytotoxic treatment in patients with hematologic malignancies (e.g., ALL, AML, or NHL).
Can also manifest unrelated to therapy in patients with a very high tumor burden

6. Pathophysiology Tumor cell lysis → release of intracellular components (e.g., K+, PO43-, nucleic acids) into the bloodstream
↑ Nucleic acid → conversion to uric acid → hyperuricemia → urate nephropathy and risk of acute kidney injury
↓ Ca2+ secondary to PO43- binding → hypocalcemia → neuronal excitability → risk of seizures
Hyperphosphatemia: PO43- binds Ca2+ and forms calcium phosphate crystals that obstruct renal tubules → acute kidney injury
Hyperkalemia: changes in resting membrane potential → risk of cardiac arrhythmias

7. Pathophysiology Think of “PUKE calcium” to remember the electrolytes affected in tumor lysis syndrome: Phosphorus, Uric acid, and potassium (K+) are Elevated; Calcium is decreased.

8. Clinical features Symptoms emerge within 72 hours post-chemotherapy: abdominal pain, urinary issues (dysuria, oliguria, hematuria , flank pain)
Hyperkalemia: e.g., cardiac arrhythmias, nausea, vomiting, and diarrhea Hypocalcemia: e.g., anorexia, vomiting, cramps, tetany, seizures, altered mental status

9. Clinical features Physical findings: carpal/pedal spasms Chvostek /Trousseau signs, wheezing (hypocalcemia); renal colic

10. Investigations Metabolic panel hyperkalemia ≥6 mEq /L, hyperphosphatemia ≥4.5 mg/dL adults, hyperuricemia ≥8 mg/dL, hypocalcemia ≤7 mg/dL,

11. Investigations Imaging : Chest X-ray/CT for mediastinal masses; abdominal CT/ultrasound for tumors (avoid IV contrast in AKI). ECG : Detects arrhythmias from hyperkalemia/hypocalcemia.

12. Diagnosis Consider TLS in any patient with hematological malignancies and hyperleukocytosis who have electrolyte imbalances, kidney failure, or recently initiated cytotoxic therapy.

13. Diagnosis Based on Cairo-Bishop criteria: Laboratory TLS requires ≥2 lab changes (e.g., uric acid ≥8 mg/dL or 25% increase, potassium ≥6 mEq /L or 25% increase, phosphorus ≥4.5 mg/dL or 25% increase, calcium ≤7 mg/dL or 25% decrease) within 3 days before to 7 days after therapy.
Clinical TLS: Laboratory criteria plus ≥1 clinical feature (arrhythmia , seizure, sudden death) not due to therapy.
Graded 0 (none) to V (death) based on severity of complications.

14. Management Identify patients with established TLS and those at high risk (e.g., hematological malignancy, chemotherapy)
Start intensive fluid therapy, uric acid reduction, and correction of electrolyte imbalances.
Consider notifying ICU, nephrology, and oncology early on.

15. Management Aggressive hydration, Rasburicase for established TLS, Hemodialysis for severe cases or advanced AKI.
Hyperkalemia: cardiac monitoring and standard therapy for hyperkalemia if K+ ≥ 6 mEq /L, e.g., glucose and insulin (rapid action)
Hyperphosphatemia: hydration and possibly oral phosphate binders, e.g., sevelamer Hypocalcemia: Treat only if symptomatic and give the lowest calcium dose to relieve symptoms.

16. Complications Acute kidney injury (AKI) from crystal nephropathy and obstructive uropathy . Cardiac arrhythmias, syncope, sudden death from hyperkalemia/hypocalcemia. Seizures, altered mental status, tetany from hypocalcemia; multi-organ failure, death (mortality up to 21%). In solid tumors : Often fatal in reported cases due to advanced disease.

17. References [13] Tumor Lysis Syndrome – StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK518985/ (Updated Oct 5, 2024)
[14] Tumor Lysis Syndrome in Solid Tumors : An up to Date Review of the Literature - PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC4083673/
Additional sources from oncology reviews (e.g., ASCO guidelines, NEJM) align with these findings but were not fully accessible for detailed extraction.