hematology and oncology
Management of Adverse Effects of Cancer Therapy
Tumor Lysis and Cytokine Release Syndromes
Tumor lysis syndrome occurs because rapid death of cancer cells, resulting from cytotoxic Chemotherapy and some types of Tumor lysis syndrome occurs mainly in leukemias and lymphomas but can also occur in other hematologic cancers and, uncommonly, after treatment of solid cancers. Active Specific Immunotherapy used to treat B-cell leukemias may precipitate life-threatening tumor lysis and cytokine release days to weeks after vaccination. Diagnostic criteriafor tumor lysis syndrome include Acute Kidney Injury (AKI) None Hypocalcemia (calcium Asymptomatic Hyperuricemia (uric acid Hyperphosphatemia (phosphorus Hyperkalemia (potassium deposition in patients with hyperphosphatemia, and a pH of > 7 should be avoided. Treatment is given depending on the serum potassium level and may involve oral potassium-lowering drugs, IV calcium, and IV glucose and Preventionof tumor lysis syndrome is desirable. Often it is possible to anticipate development of tumor lysis syndrome (eg, when treating cancers with rapid cell turnover) and to give large volumes of fluids andallopurinolorrasburicasebefore starting chemotherapy and sometimes prior to immune therapy (such as bispecific monoclonal antibodies or CAR-T-cells) to protect the kidneys from damage from uric acid. Patients should receive vigorous IV hydration to establish a urine output of at least 100 mL/hour before treatment. Patients also should receiveallopurinolfor at least 2 days before and during chemotherapy; for patients with high cell burden, this regimen can be continued for 10 to 14 days after therapy.Rasburicaseis an enzyme that oxidizes uric acid to allantoin (a more soluble molecule) and is given at 0.15 to 0.2 mg/kg IV over 30 minutes once a day for 5 to 7 days, typically started 4 to 24 hours before the first chemotherapy treatment. Adverse effects may include anaphylaxis, hemolysis, hemoglobinuria, and methemoglobinemia. Guidelines regarding evaluation and management of tumor lysis syndrome are available ( Tumor lysis syndrome and cytokine release syndrome references ). Cytokine release syndrome (CRS) is related to but distinct from tumor lysis syndrome. Cytokine release syndrome occurs when large numbers of immune cells are activated and release inflammatory cytokines, including interleukin (IL)-6 and interferon gamma. It is a frequent complication of Immune Therapy such as bi-specific monoclonal antibodies or CAR-T-cells. Clinical features include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rash, and headache. Tachypnea, tachycardia, hypotension, tremor, loss of coordination, seizures, and delirium may occur. Typical features include Hypoxia Widened pulse pressure Increased or decreased cardiac output Increased bloodureanitrogen (BUN), D-dimer, liver enzymes, and bilirubin Low fibrinogen level Grading of cytokine release syndrome ( Tumor lysis syndrome and cytokine release syndrome references ) is as follows: Grade 1: Symptoms (eg, fever, nausea, fatigue, headache, myalgias, malaise) are not life-threatening and require symptomatic treatment only. Grade 2: Symptoms require and respond to moderate intervention with oxygen supplementation up to 40% FiO2, or hypotension that is responsive to fluids or low-dose vasopressor, or grade 2 organ toxicity. Grade 3: Symptoms require and respond to aggressive intervention with oxygen supplementation ≥ 40% FiO2, or hypotension requires high-dose or multiple vasopressors, or grade 3 organ toxicity, or grade 4 transaminitis. Grade 4: Symptoms are life threatening, including need for ventilator support, or indicate grade 4 organ toxicity (excluding transaminitis). Grade 5: Death Therapy of low-grade CRS is supportive. Moderate-grade CRS requires oxygen therapy and fluids and one or more antihypotensive drugs to raise blood pressure. Moderate and severe-grade (ie, grades 3 and 4) CRS are treated with immune suppressive drugs such as corticosteroids.Tocilizumab, an anti-interleukin-6 (IL-6) monoclonal antibody, is also used in severe CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) is a neuropsychiatric syndrome that can occur in some cancer patients treated with immune therapy. It is also related to cytokine-mediated toxicity and has been called cytokine release encephalopathy syndrome (CRES). Symptoms include confusion, depressed level of consciousness, disturbance in attention, lethargy, mental status changes, delirium, dizziness, muscle spasms, and muscle weakness ( Tumor lysis syndrome and cytokine release syndrome references ). Mild neurotoxicity is managed supportively. More severe neurotoxicity is treated withdexamethasoneormethylprednisolone. Patients with severe neurotoxicity may need treatment in the intensive care unit. 1.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 Haematol149(4):578–586, 2010. doi: 10.1111/j.1365-2141.2010.08143.x 2.Coiffier B, Altman A, Pui CH, et al: Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review.J Clin Oncol26(16):2767–2778, 2008. doi: 10.1200/JCO.2007.15.0177 3.Lee DW, Santomasso BD, Locke FL, et al: ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells.Biol Blood Marrow Transplant25(4):625–638, 2019. doi: 10.1016/j.bbmt.2018.12.758 