Tumour lysis syndrome

Risk stratification for TLS[37]Cairo MS, Coiffier B, Reiter A, et al. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010 May;149(4):578-86. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2010.08143.x http://www.ncbi.nlm.nih.gov/pubmed/20331465?tool=bestpractice.com ​​

Patients can be categorised as low, intermediate, or high risk depending on the type of malignancy, treatment sensitivity (of the tumour), disease stage, white blood cell (WBC) count, tumour burden (bulk), lactate dehydrogenase (LDH) levels, and pre-existing renal impairment/renal abnormality.

Low-risk patients include those with:

• Solid tumours, except rare solid tumours that are chemosensitive (e.g., neuroblastoma, germ cell tumours, small cell lung cancer), or others with bulky or advanced disease

• Chronic myeloid leukaemia: chronic phase

• Chronic lymphocytic leukaemia when treated exclusively with alkylating agents

• Multiple myeloma

• Hodgkin's lymphoma

• Acute myeloid leukaemia with WBC count <25 × 10⁹/L (<25,000/microlitre) and LDH <2 times the upper limit of normal (ULN)

• Indolent/low proliferating non-Hodgkin's lymphoma (e.g., small lymphocytic lymphoma, follicular lymphoma, marginal B-cell lymphoma, MALT lymphoma, mantle cell lymphoma [non-blastoid], cutaneous T-cell lymphoma, and anaplastic large cell lymphoma [adults])

Patients with low-risk disease who have renal dysfunction/involvement should be categorised as intermediate risk.

Intermediate-risk patients include those with:

• Rare solid tumours that are chemosensitive (e.g., neuroblastoma, germ cell tumours, small cell lung cancer), or others with bulky or advanced-stage disease

• Early-stage Burkitt's lymphoma with LDH <2 times the ULN

• Early-stage lymphoblastic lymphoma with LDH <2 times ULN

• Acute lymphoblastic leukaemia with WBC count <100 × 10⁹/L (<100,000/microlitre) and LDH <2 times ULN

• Acute myeloid leukaemia with WBC count ≥25 × 10⁹/L (≥25,000/microlitre) to <100 × 10⁹/L (<100,000/microlitre), or WBC count <25 × 10⁹/L (<25,000/microlitre) and LDH ≥2 times ULN

• Chronic lymphocytic leukaemia with WBC count ≥50 × 10⁹/L (≥50,000/microlitre) and/or treated with fludarabine or targeted agents (e.g., rituximab, lenalidomide, obinutuzumab, venetoclax)

Patients with intermediate-risk disease who have renal dysfunction/involvement, or uric acid, potassium, and/or phosphate levels above the normal range, should be categorised as high risk.

High-risk patients include those with:

• Certain high-grade non-Hodgkin's lymphoma (e.g., advanced-stage Burkitt's lymphoma or lymphoblastic lymphoma) and bulky high-grade non-Hodgkin's lymphoma (e.g., diffuse large B-cell lymphoma)

• Acute lymphoblastic leukaemia with WBC count ≥100 × 10⁹/L (≥100,000/microlitre), or WBC count <100 × 10⁹/L (<100,000/microlitre) and LDH ≥2 times ULN

• Acute myeloid leukaemia with WBC count ≥100 × 10⁹/L (≥100,000/microlitre)

• Chronic lymphocytic leukaemia treated with venetoclax if there is a high tumour burden (lymph node ≥10 cm or lymph node ≥5 cm and absolute lymphocyte count [ALC] ≥25,000/microlitre) or a medium tumour burden (lymph node 5 cm to <10 cm; or ALC ≥25 × 10⁹/L [≥25,000/microlitre]) in those with creatinine clearance <1.34 mL/s (<80 mL/min)

Cairo and Bishop grading classification for TLS (2004)[2]Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004 Oct;127(1):3-11. https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2004.05094.x http://www.ncbi.nlm.nih.gov/pubmed/15384972?tool=bestpractice.com

Grade 0

• No laboratory TLS; creatinine ≤1.5 times ULN; no clinical manifestations.

Grade 1

• Laboratory TLS; creatinine 1.5 times ULN; cardiac arrhythmia but medical intervention is not indicated; no seizure activity.

Grade 2

• Laboratory TLS; creatinine >1.5 to 3.0 times ULN; cardiac arrhythmia requiring non-urgent medical intervention; one brief generalised seizure, or seizures well controlled by anticonvulsants, or infrequent focal motor seizures not interfering with activities of daily living.

Grade 3

• Laboratory TLS; creatinine >3 to 6 times ULN, cardiac arrhythmias symptomatic and incompletely controlled medically or requiring a device (e.g., defibrillator); seizure activity with altered consciousness or poorly controlled seizure disorder with breakthrough generalised seizures.

Grade 4

• Laboratory TLS; creatinine >6 times ULN; life-threatening arrhythmia associated with heart failure, hypotension, syncope, or shock; seizure activity that is prolonged, repetitive, or difficult to control.

Grade 5

• Laboratory TLS and death.