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heme.tumor-lysis-syndrome.core.v1

Tumor Lysis Syndrome (TLS)

hematologyacuteadultacuteinpatient
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Tumor lysis syndrome dossier. STEP 3 deepened (2026-05-16). 2026-05-22 PMID+RxCUI remediation (live-verified): Cairo-Bishop 15051767(=colorectal-cancer survival JCO)->15384972 (Br J Haematol 2004 classification); removed fabricated "ASCO 2024 Howard" PMID 38194618(=monoclonal-antibody adsorption Mol Pharm) entirely — no such guideline exists, all 147 inline "ASCO 2024 Howard" labels reworded to the verified Coiffier JCO 2008 consensus; Coiffier 21747150(=multifocal-fibrosclerosis case report)->18509186 (the real Coiffier JCO 2008, already in the list — duplicate consolidated); Goldman 11342417(=cord-blood transplant Blood)->11342423 (the real rasburicase-vs-allopurinol RCT). RxCUI fixes (RxNav reverse-lookup): rasburicase 358896(invalid)->283821, calcium gluconate 4850(=glucose)->1908, regular insulin 5856(invalid)->253182, sodium polystyrene sulfonate 35936(invalid)->56512, patiromer 2284718(=remdesivir)->1716203, sevelamer 18600(=azatadine)->214824, aluminum hydroxide 215167(invalid)->612; allopurinol 519 confirmed correct. §5.5.1 effect sizes (rasburicase 4-h urate ↓86% vs allopurinol ↓12% Goldman; lab-TLS ~18-26% / clinical-TLS ~3-6% Howard NEJM 2011). last_reconciled 2026-05-22.

Entry points (3)

  • lab_abnormality
    Lab TLS: >=2 of uric acid >=8, K >=6, PO4 >=4.5, Ca <=7 (or 25% change from baseline) within 3 days before or 7 days after cytotoxic therapy — Cairo-Bishop JCO 2004
    hyperuricemia_hyperK_hyperPO4_hypoCa
  • symptom
    Clinical TLS: lab TLS + renal failure (Cr >=1.5x ULN), cardiac arrhythmia, seizure, or sudden death — Cairo-Bishop JCO 2004
    clinical_tls
  • problem_list
    High-risk malignancy (Burkitt, ALL with WBC >100K, DLBCL with bulky disease) before initiating cytotoxic therapy — Coiffier JCO 2008; NCCN 2024
    high_risk_malignancy_pre_chemo

Required inputs (11)

  • uric_acidrequired
    lab • used at ENTRY
    Cairo-Bishop criterion: uric acid >=8 mg/dL or 25% increase — Cairo-Bishop JCO 2004; Coiffier JCO 2008
  • potassiumrequired
    lab • used at ENTRY
    Cairo-Bishop criterion: K >=6 mEq/L or 25% increase; hyperK drives cardiac toxicity — Cairo-Bishop JCO 2004; Coiffier JCO 2008
  • phosphorusrequired
    lab • used at ENTRY
    Cairo-Bishop criterion: PO4 >=4.5 mg/dL (adults) or 25% increase; drives calcium-phosphate deposition — Cairo-Bishop JCO 2004; Coiffier JCO 2008
  • calciumrequired
    lab • used at ENTRY
    Cairo-Bishop criterion: corrected Ca <=7 mg/dL or 25% decrease; secondary to hyperphosphatemia — Cairo-Bishop JCO 2004; Coiffier JCO 2008
  • creatininerequired
    lab • used at ENTRY
    Clinical TLS: Cr >=1.5x ULN defines renal involvement; uric acid nephropathy and calcium-phosphate deposition — Cairo-Bishop JCO 2004; Coiffier JCO 2008
  • ldhrequired
    lab • used at CONTEXT
    Tumor burden marker; high LDH predicts TLS risk — Coiffier JCO 2008; NCCN 2024
  • agerequired
    demographic • used at CONTEXT
    Pediatric dosing differs; elderly have less renal reserve — Coiffier JCO 2008
  • malignancy_typerequired
    history • used at RISK_STRATIFICATION
    Risk stratification: Burkitt/ALL/DLBCL = high risk; AML = intermediate; solid tumors = generally low — Coiffier JCO 2008; NCCN 2024
  • wbcrequired
    lab • used at RISK_STRATIFICATION
    WBC >50-100K increases TLS risk (high tumor burden) — Coiffier JCO 2008; NCCN 2024
  • ecg
    imaging • used at RED_FLAGS
    HyperK cardiac toxicity: peaked T waves, widened QRS, sine wave — Cairo-Bishop JCO 2004; Coiffier JCO 2008
  • urine_outputrequired
    lab • used at MONITORING
    Oliguria/anuria signals AKI from uric acid or CaPO4 deposition; guides IVF rate and RRT decision — Coiffier JCO 2008

12-phase flow (12)

  1. 1FRAME
    Identify setting: pre-treatment prophylaxis vs active TLS treatment; confirm malignancy type and planned/initiated cytotoxic therapy — Coiffier JCO 2008; NCCN 2024
    inputs: malignancy_type
    advance: Clinical scenario framed (prevention vs treatment)
  2. 2ENTRY
    Apply Cairo-Bishop 2004 laboratory TLS criteria: >=2 of uric acid >=8, K >=6, PO4 >=4.5, Ca <=7 (or 25% change); classify as lab TLS vs clinical TLS (+ renal failure, arrhythmia, seizure) — Cairo-Bishop JCO 2004
    inputs: uric_acid, potassium, phosphorus, calcium, creatinine
    advance: Cairo-Bishop classification assigned
  3. 3CONTEXT
    Tumor type, tumor burden (LDH, WBC, bulky disease), baseline renal function, baseline uric acid, hydration status, concomitant nephrotoxins, prior TLS episodes — Coiffier JCO 2008; NCCN 2024
    inputs: age, ldh, malignancy_type
    advance: Risk context gathered
  4. 4RED_FLAGS
    Hyperkalemia with ECG changes (peaked T, wide QRS, sine wave — emergency); symptomatic hypocalcemia (tetany, seizure, QTc prolongation); oliguria/anuria; cardiac arrhythmia — Cairo-Bishop JCO 2004; Coiffier JCO 2008
    inputs: potassium, calcium, ecg
    advance: Life-threatening electrolyte emergencies triaged
  5. 5INITIAL_WORKUP
    STAT: BMP (K, Ca, PO4, Cr, BUN), uric acid, LDH, CBC with diff, coag, urinalysis, ECG; calculate Ca x PO4 product (>60 = high deposition risk) — Cairo-Bishop JCO 2004; Coiffier JCO 2008; NCCN 2024
    inputs: uric_acid, potassium, phosphorus, calcium, creatinine, ldh
    actions: panel.renal, panel.cbc
    advance: Baseline labs complete + ECG reviewed
  6. 6BRANCHING_WORKUP
    Renal ultrasound if AKI (obstruction vs intrinsic); echocardiogram if arrhythmia/HF; repeat labs q4-6h for trending — Coiffier JCO 2008; NCCN 2024
    advance: Additional studies sent if AKI or cardiac involvement
  7. 7DIFFERENTIAL
    Bayesian pivots — TLS favoured by markedly elevated uric acid (commonly >15 mg/dL) + hyperphosphatemia + temporal link (-3 to +7 days of cytotoxic therapy) + high tumor burden (LDH, WBC); urinary uric-acid:creatinine ratio >1 favours acute urate nephropathy over other AKI. Look-alikes with named pivots: rhabdomyolysis (CK markedly elevated + myoglobinuria, urate less extreme, no chemo link), contrast nephropathy (recent iodinated contrast, bland sediment), obstructive uropathy (hydronephrosis on US), drug-induced AKI (calcineurin inhibitor exposure), adrenal crisis (hyponatremia + hyperK without hyperPO4/hyperuricemia) — Howard NEJM 2011 (PMID 21561350); Coiffier JCO 2008 (PMID 18509186)
    advance: TLS confirmed as primary etiology and look-alikes pivoted out
  8. 8RISK_STRATIFICATION
    HIGH (laboratory TLS ~18-26%, clinical TLS ~3-6% — Howard NEJM 2011 PMID 21561350): Burkitt lymphoma, ALL/AML with WBC >100K, DLBCL with bulky disease + elevated LDH, any tumor with baseline uric acid >7.5 or Cr >1.4 — rasburicase prophylaxis. INTERMEDIATE: AML with WBC 25-100K, ALL with WBC <100K, DLBCL non-bulky — allopurinol + aggressive IVF. LOW: solid tumors, CLL, indolent NHL — monitoring + hydration. MODERN: venetoclax (CLL/AML) ramp-up is now a leading targeted-therapy TLS trigger requiring risk-adapted debulk + hydration ± rasburicase — NCCN 2024; Howard NEJM 2011 (PMID 21561350); Coiffier JCO 2008 (PMID 18509186)
    inputs: malignancy_type, wbc, ldh
    advance: Risk tier assigned (high/intermediate/low)
  9. 9TREATMENT
    PREVENTION: Low risk — hydration + monitoring. Intermediate — allopurinol 300-800mg/day PO + aggressive IVF (2.5-3 L/m2/day). High — rasburicase 0.2 mg/kg IV single dose + aggressive IVF. TREATMENT (established TLS): rasburicase 0.2 mg/kg IV (repeat q12-24h PRN); aggressive IVF 200-250 mL/h; hyperK management (calcium gluconate, insulin/dextrose, kayexalate, emergent RRT if refractory); phosphate binders if hyperPO4; AVOID calcium unless symptomatic (drives CaPO4 deposition); RRT for refractory hyperK, volume overload, severe AKI — Coiffier JCO 2008; Cairo-Bishop JCO 2004; NCCN 2024
    actions: protocol.hyperkalemia.emergency.v1
    advance: Treatment initiated per risk tier
  10. 10DISPOSITION
    High-risk prophylaxis: monitored bed or ICU. Established clinical TLS: ICU for cardiac monitoring + possible RRT. Lab TLS without clinical features: telemetry floor — Coiffier JCO 2008; NCCN 2024
    advance: Disposition set
  11. 11MONITORING
    Labs (K, Ca, PO4, uric acid, Cr, LDH) q4-6h during active TLS or first 48-72h of high-risk chemotherapy; strict I/O with target UOP >=2 mL/kg/h; continuous telemetry for hyperK; repeat ECG if K >6 — Coiffier JCO 2008; Cairo-Bishop JCO 2004; NCCN 2024
    inputs: uric_acid, potassium, phosphorus, calcium, creatinine, urine_output
    actions: panel.renal
    advance: Electrolytes normalizing + adequate UOP
  12. 12FOLLOWUP
    Transition to daily labs once stable; resume chemotherapy when TLS resolved + electrolytes normalized + renal function recovered; document TLS episode for future cycle risk assessment; dose-adjust or change chemo regimen if recurrent TLS — Coiffier JCO 2008; NCCN 2024
    advance: TLS resolved + chemo plan adjusted