😱Emergencies in Hematolo...
Highlights
- 😱Emergencies in hematology😱
Tumor lysis syndrome (TLS)
A short 🧵 #MedTwitter
1/19
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- What's TLS?
-major comorbidity in the management of hematologic malignancies and one of the major conditions young colleagues should
👉know to detect and to handle❗️
-modern definition of TLS is based on the Cairo–Bishop criteria for laboratory and clinical TLS
2/19
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- Clinical TLS:
-simply defined as laboratory TLS with the addition of an elevated creatinine not attributable to
- History:
-phenomenon of chemotherapy-induced TLS became apparent soon after effective therapies for leukemia and lymphoma were discovered early in 20th century
-several reports published describing uric acid nephropathy and acute failure within days after treatment
4/19
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- Pathogenesis I:
-lysis of tumour cells👉release of cell contents, incl electrolytes, proteins and nucleic acids
- nucleic acid and protein contents are quickly broken down in the liver👉production of uric acid
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- Pathogenesis II:
-release of potassium & phosphorus
-rapid increases in potassium, sometimes potentiated by renal failure👉arrhythmias -hypocalcaemia (Ca2+ phosphorus precipitation & tissue deposition)👉muscle cramps, tetany, arrhythmias, seizures
6/19
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- Pathogenesis III:
-mechanism behind acute injury is multi-factorial -hyperuricemia👉direct crystallization within renal tubules
-uric acid-induced renal vasoconstriction tissue hypoxia, reperfusion injury & local inflammation
7/19
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- Risk stratification:
-serum creatinine, arrhythmia and/or seizures, with the most severe clinical sequela determining the grade
BUT
-expert opinion, not validated prospectively
-acute failure >50% but only ~1% show seizures
8/19
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- In general:
-severity of TLS may depend on the cancer mass, potential for lysis of tumor cells, characteristics of the patient and supportive care
-the greater the cancer mass, the greater the quantity of cellular contents released after anticancer therapy
9/19 https://t.co/BW4h314zG9 (View Tweet)
- Patient history matters!
-perhaps a more clinically relevant is identification of patients at highest risk
-CML considered low-risk, as is CLL
BUT
iCLL classified as intermediate-risk if WBC >50×10^9/l or if treated with targeted therapies such as venetoclax
10/19
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- Drug-associated TLS (selection):
-all anti-CD20 monoclonal antibody therapies
-ibrutinib, lenalidomide, pazopanib, trastuzumab
-venetoclax (ramp-up!)
-paclitaxel, radiation, corticosteroids, fludarabine, immune checkpoint inhibitors...
11/19
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- Prevention:
-CRITICAL
-hydration is backbone for prevention/treatment
-
- goal: improve volume status and create the optimal environment forexcretion of uric acid and phosphate
-
- rules of 👍 i~3 l/m2/day or targeting urine output of at least 100–150 ml/h
12/19
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- Controversy "urine alkalization":
-may prevent uric acid crystal formation
BUT
-can ⬇️xanthine solubility👉promote crystal formation
-can ⬆️Ca2+ phosphate precipitates
-allopurinol can lead to xanthinuria
-alkalization+allopurinol not currently recommended
13/19 https://t.co/UTfXf2tHRL (View Tweet)
- Allopurinol:
-xanthine oxidase inhibitor
- -⬇️serum uric acid levels
-
- ⬇️risk of uric acid crystallization and acute renal failure
-recommended: daily for adults 600–800 mg (into 2–3 doses)
-lower dose eg 300 mg often utilized
-started 1–2 days prior to chemo + hydration
14/19
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- Rasburicase:
-recombinant urate oxidase
-converting uric acid to allantoin
-rapid and high efficacy (median 1 day)
BUT
-no randomized trial showed superiority vs allopurinol
-recommended for high risk
-general practice: if the baseline uric acid is >8 mg/dl
15/19
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- CAVE:
-patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) are at risk for acute haemolytic anaemia after administration of rasburicase
-FDA recommends performing G6PD enzyme activity testing in patients at higher risk for G6PD deficiency
16/19
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- Febuxostat:
-another oral xanthine oxidase inhibitor
-pharmacologic advantage over allopurinol: inhibits both oxidized+reduced form of xanthine oxidase👉potency⬆️ and no need for dose adjustment in renal failure
BUT
-FLORENCE trial showed NO difference to allopurinol
17/19
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- Prognosis:
-often not the principle cause of mortality (infections, sepsis!)
-eg in AML, only ~5% show clinical TLS
BUT
👉 associated with a much higher death rate (~70% vs 25% for laboratory)
-adapt for risk and patient characteristics❗️
18/19 https://t.co/UmHoCVlnU4 (View Tweet)
- TLS summary:
❗️Emergency
❗️Monitor: lab+clinical (🫘 failure, 🫀arrhythmias, seizures)
❗️Risk stratify: disease, morbidity, treatment
❗️Secure venous access
❗️Prevention/treatment: HYDRATION, allopurinol for lower and +rasburicase for higher risk
#MedTwitter https://t.co/G5j6j6ZeWj (View Tweet)
- References & resources:
https://t.co/HDvz3pTngD
https://t.co/nBnTcTTQVp
https://t.co/oDUJqIWf2H
https://t.co/rgtKgkiyuL https://t.co/R1G9Lb8ZPj (View Tweet)