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heme.tumor-lysis-syndrome.core.v1PRODUCTION
heme.tumor-lysis-syndrome.core.v1

Tumor Lysis Syndrome (TLS)

hematologyacuteadult
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Identify setting: pre-treatment prophylaxis vs active TLS treatment; confirm malignancy type and planned/initiated cytotoxic therapy — Coiffier JCO 2008; NCCN 2024

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Clinical scenario framed (prevention vs treatment)

Patient inputs (11)

Tumor burden marker; high LDH predicts TLS risk — Coiffier JCO 2008; NCCN 2024

Pediatric dosing differs; elderly have less renal reserve — Coiffier JCO 2008

Cairo-Bishop criterion: uric acid >=8 mg/dL or 25% increase — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Cairo-Bishop criterion: K >=6 mEq/L or 25% increase; hyperK drives cardiac toxicity — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Cairo-Bishop criterion: PO4 >=4.5 mg/dL (adults) or 25% increase; drives calcium-phosphate deposition — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Cairo-Bishop criterion: corrected Ca <=7 mg/dL or 25% decrease; secondary to hyperphosphatemia — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Clinical TLS: Cr >=1.5x ULN defines renal involvement; uric acid nephropathy and calcium-phosphate deposition — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Oliguria/anuria signals AKI from uric acid or CaPO4 deposition; guides IVF rate and RRT decision — Coiffier JCO 2008

Risk stratification: Burkitt/ALL/DLBCL = high risk; AML = intermediate; solid tumors = generally low — Coiffier JCO 2008; NCCN 2024

WBC >50-100K increases TLS risk (high tumor burden) — Coiffier JCO 2008; NCCN 2024

HyperK cardiac toxicity: peaked T waves, widened QRS, sine wave — Cairo-Bishop JCO 2004; Coiffier JCO 2008

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (5)

5 need judgement
  • informationallife_threateninghyperK_ecg_changes
    K >=6 mEq/L with ECG changes (peaked T waves, widened QRS, sine wave) in TLS — Cairo-Bishop JCO 2004; Coiffier JCO 2008
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcardiac_arrhythmia_tls
    Cardiac arrhythmia attributable to TLS electrolyte derangements — Cairo-Bishop JCO 2004
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningseizure_hypocalcemia
    Seizure from symptomatic hypocalcemia (corrected Ca <=7 mg/dL with neuromuscular irritability) in TLS — Cairo-Bishop JCO 2004; Coiffier JCO 2008
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereclinical_tls_renal_failure
    Clinical TLS with AKI (Cr >=1.5x ULN) — Cairo-Bishop JCO 2004; Coiffier JCO 2008
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatehigh_risk_malignancy_pre_chemo
    High-risk malignancy (Burkitt, ALL WBC >100K, bulky DLBCL) about to start chemotherapy — Coiffier JCO 2008; NCCN 2024
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

TLS prevention: allopurinol + IVF (intermediate risk) vs rasburicase + IVF (high risk) — Coiffier JCO 2008; NCCN 2024
axis: tls_preventionstep low_risk - Low risk — hydration + monitoring only
Selected step "Low risk — hydration + monitoring only" — Solid tumors, CLL, indolent NHL, low tumor burden — Coiffier JCO 2008; NCCN 2024
  • IV_hydration
    first line
    fluid_therapy
    NS or LR at 150-200 mL/h (2-2.5 L/m2/day) • IV • continuous
    Coiffier JCO 2008 — maintain UOP >=2 mL/kg/h; dilute uric acid and phosphate

ed playbook — drug actions (4)

  1. 1. aggressive IVF
    NS 200-250 mL/h • IV • continuous
    trigger: TLS suspected or confirmed — Coiffier JCO 2008
    Coiffier JCO 2008 — cornerstone; target UOP >=2 mL/kg/h
  2. 2. rasburicase
    0.2 mg/kg IV over 30 min • IV • single dose
    trigger: Established TLS or high-risk with elevated uric acid — Coiffier JCO 2008
    Coiffier JCO 2008 — rapid uric acid reduction; check G6PD; ice samples
  3. 3. calcium gluconate
    1-2 g IV over 5-10 min • IV • PRN
    trigger: K >=6.5 with ECG changes — Cairo-Bishop JCO 2004
    Cairo-Bishop JCO 2004 — cardiac membrane stabilization; does not lower K
  4. 4. insulin + dextrose
    10 units regular insulin IV + D50W 25g • IV • once; repeat PRN
    trigger: K >=6 — Coiffier JCO 2008
    Coiffier JCO 2008 — intracellular K shift; monitor glucose q1h

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: 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; Clinical TLS: lab TLS + renal failure (Cr >=1.5x ULN), cardiac arrhythmia, seizure, or sudden death — Cairo-Bishop JCO 2004; High-risk malignancy (Burkitt, ALL with WBC >100K, DLBCL with bulky disease) before initiating cytotoxic therapy — Coiffier JCO 2008; NCCN 2024.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Tumor Lysis Syndrome (TLS)** (heme.tumor-lysis-syndrome.core.v1).
Phenotype framing: 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)
Scope: Identify setting: pre-treatment prophylaxis vs active TLS treatment; confirm malignancy type and planned/initiated cytotoxic therapy — Coiffier JCO 2008; NCCN 2024

No severity triggers fired against current inputs.

Plan

Regimen axis: **TLS prevention: allopurinol + IVF (intermediate risk) vs rasburicase + IVF (high risk) — Coiffier JCO 2008; NCCN 2024** — step "Low risk — hydration + monitoring only".
1. IV_hydration NS or LR at 150-200 mL/h (2-2.5 L/m2/day) IV continuous (fluid_therapy, first line) — Coiffier JCO 2008 — maintain UOP >=2 mL/kg/h; dilute uric acid and phosphate

Setting playbook (ed) — Identify TLS via Cairo-Bishop criteria, initiate aggressive IVF, manage life-threatening hyperK, start rasburicase if established TLS — Cairo-Bishop JCO 2004; Coiffier JCO 2008
2. aggressive IVF NS 200-250 mL/h IV continuous — TLS suspected or confirmed — Coiffier JCO 2008 (Coiffier JCO 2008 — cornerstone; target UOP >=2 mL/kg/h)
3. rasburicase 0.2 mg/kg IV over 30 min IV single dose — Established TLS or high-risk with elevated uric acid — Coiffier JCO 2008 (Coiffier JCO 2008 — rapid uric acid reduction; check G6PD; ice samples)
4. calcium gluconate 1-2 g IV over 5-10 min IV PRN — K >=6.5 with ECG changes — Cairo-Bishop JCO 2004 (Cairo-Bishop JCO 2004 — cardiac membrane stabilization; does not lower K)
5. insulin + dextrose 10 units regular insulin IV + D50W 25g IV once; repeat PRN — K >=6 — Coiffier JCO 2008 (Coiffier JCO 2008 — intracellular K shift; monitor glucose q1h)

Non-pharmacologic actions:
- Foley catheter for strict I/O monitoring (Coiffier JCO 2008)
- Continuous telemetry (Cairo-Bishop JCO 2004)
- Oncology + nephrology STAT consults (Coiffier JCO 2008)
- AVOID calcium supplementation unless symptomatic hypocalcemia (seizure, tetany) (Cairo-Bishop JCO 2004; Coiffier JCO 2008)

AVOID / contraindication checks:
- Rasburicase G6PD contraindicated (Coiffier JCO 2008; NCCN 2024 — G6PD deficiency causes methemoglobinemia + hemolytic anemia; screen before use)
- Rasburicase ice sample (Coiffier JCO 2008 — uric acid sample must be placed on ice immediately to prevent ex vivo degradation by rasburicase)
- Allopurinol no existing uric acid reduction (Coiffier JCO 2008 — allopurinol only prevents new uric acid formation; does NOT reduce existing levels; use rasburicase for hyperuricemia)
- Avoid urine alkalinization (Coiffier JCO 2008 — previously recommended but now discouraged; promotes calcium phosphate precipitation)
- Avoid calcium supplementation unless symptomatic (Cairo Bishop JCO 2004; Coiffier JCO 2008 — exogenous calcium drives CaPO4 deposition in kidneys/tissues)

Monitoring

Regimen monitoring:
- K, Ca, PO4, uric acid, Cr, LDH q4-6h during active TLS or first 48-72h post-chemo — Coiffier JCO 2008; NCCN 2024
- Strict I/O: target UOP >=2 mL/kg/h — Coiffier JCO 2008
- Continuous telemetry for hyperK (peaked T waves, widened QRS) — Cairo-Bishop JCO 2004
- ECG if K >6 mEq/L — Cairo-Bishop JCO 2004; Coiffier JCO 2008
- Ca x PO4 product (>60 = high deposition risk) — Cairo-Bishop JCO 2004
- Uric acid on ice if rasburicase given — Coiffier JCO 2008

Setting (ed) monitoring:
- K, Ca, PO4, uric acid, Cr q4-6h — Coiffier JCO 2008
- Continuous cardiac telemetry — Cairo-Bishop JCO 2004
- UOP q1h — Coiffier JCO 2008
- Glucose q1h after insulin/dextrose — Coiffier JCO 2008

Follow-up plan: 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
- Close-out criterion: TLS resolved + chemo plan adjusted

Monitoring phase: 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

Disposition

Current setting: ed — Identify TLS via Cairo-Bishop criteria, initiate aggressive IVF, manage life-threatening hyperK, start rasburicase if established TLS — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Disposition criteria:
- Established clinical TLS → ICU for cardiac monitoring + possible RRT — Coiffier JCO 2008
- Lab TLS only → telemetry floor with q4-6h labs — Coiffier JCO 2008
- High-risk pre-chemo prophylaxis → monitored bed — NCCN 2024

Escalation triggers (move to higher acuity):
- Refractory hyperK (K >6.5 despite medical therapy) → nephrology for RRT — Coiffier JCO 2008; NCCN 2024
- Cardiac arrhythmia → ICU + cardiology — Cairo-Bishop JCO 2004
- Seizure from hypocalcemia → ICU + treat symptomatic hypoCa — Cairo-Bishop JCO 2004; Coiffier JCO 2008
- Oliguria/anuria despite aggressive IVF → RRT — Coiffier JCO 2008

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] K >=6 mEq/L with ECG changes (peaked T waves, widened QRS, sine wave) in TLS — Cairo-Bishop JCO 2004; Coiffier JCO 2008
- [LIFE_THREATENING] Cardiac arrhythmia attributable to TLS electrolyte derangements — Cairo-Bishop JCO 2004
- [LIFE_THREATENING] Seizure from symptomatic hypocalcemia (corrected Ca <=7 mg/dL with neuromuscular irritability) in TLS — Cairo-Bishop JCO 2004; Coiffier JCO 2008

Citations

- Cairo-Bishop TLS classification (Br J Haematol 2004); Coiffier et al TLS expert consensus (JCO 2008); Howard/Jones/Pui TLS review (NEJM 2011); NCCN Management of Tumor Lysis Syndrome [PMID:15384972](https://pubmed.ncbi.nlm.nih.gov/15384972/)
- Cited evidence (PMID 21561350) [PMID:21561350](https://pubmed.ncbi.nlm.nih.gov/21561350/)
- Cited evidence (PMID 18509186) [PMID:18509186](https://pubmed.ncbi.nlm.nih.gov/18509186/)
- Cited evidence (PMID 11342423) [PMID:11342423](https://pubmed.ncbi.nlm.nih.gov/11342423/)

Last reconciled with current guidelines: 2026-05-22.
References
  • Cairo-Bishop TLS classification (Br J Haematol 2004); Coiffier et al TLS expert consensus (JCO 2008); Howard/Jones/Pui TLS review (NEJM 2011); NCCN Management of Tumor Lysis Syndrome — PMID:15384972
  • Cited evidence (PMID 21561350) — PMID:21561350
  • Cited evidence (PMID 18509186) — PMID:18509186
  • Cited evidence (PMID 11342423) — PMID:11342423