Tumor Lysis Syndrome: Practice Essentials, Pathophysiology, Etiology

Tumor lysis syndrome occurs most often in patients with acute leukemia with high white blood cell (WBC) counts and in those with high-grade lymphomas, in response to aggressive treatment. Tumor lysis syndrome may also occur in other hematologic malignancies and in a variety of solid tumors such as hepatocellular carcinoma, lung cancer, and melanoma (especially when metastatic); neuroblastoma; and germ cell tumors. [7, 8] It occasionally occurs spontaneously, prior to any form of therapy. [1, 5]

Patients at highest risk are those with bulky, rapidly proliferating tumors that are sensitive to treatment. An elevated pretreatment lactate dehydrogenase (LDH) level, which correlates with high tumor volume, is a strong prognostic indicator for developing clinically significant complications of therapy. The presence of kidney insufficiency prior to therapy also correlates with an increased likelihood of tumor lysis syndrome.

An international consensus expert panel has proposed a classification that stratifies cancers into high, intermediate, or low risk for tumor lysis syndrome. [7] The high-risk group of cancers includes the following:

• Advanced Burkitt lymphoma/leukemia or early-stage disease with elevated baseline LDH
• Acute lymphocytic leukemia (ALL) with WBC count ≥ 100,000/µL, or less if the baseline elevation of LDH is twice the upper limit of normal (ULN)
• Acute myeloid leukemia (AML) with WBC count ≥10000/µL
• Diffuse large B-cell lymphoma with an elevated baseline LDH of twice ULN and bulky disease

Intermediate-risk malignancies include the following:

• AML with WBC of 25,000-100,000/µL
• ALL with WBC < 100,000/µL and an LDH of less than twice ULN
• Early-stage Burkitt lymphoma/leukemia with an LDH of less than twice ULN
• Diffuse large B-cell lymphoma with a baseline increase in LDH of twice ULN but non-bulky disease

Low-risk diseases include the following:

• Indolent lymphomas
• Chronic lymphocytic leukemia
• Chronic myeloid leukemia in the chronic phase
• AML with WBC count < 25,000/µL and an LDH elevated to less than twice ULN
• Multiple myeloma
• Solid tumors

Reports exist of tumor lysis syndrome associated with the administration of radiation therapy, [15] corticosteroids, hormonal agents, biologic response modifiers, and monoclonal antibodies. [10] Agents reported to cause tumor lysis syndrome include the following:

• Paclitaxel
• Fludarabine
• Etoposide
• Thalidomide [16]
• Bortezomib [17]
• Zoledronic acid [18]
• Hydroxyurea
• Carfilzomib [19]
• Sorafenib [20]
• Venetoclax [21]

The development of tumor lysis syndrome is not limited to the systemic administration of agents; it can occur with intrathecal administration of chemotherapy and with chemo-embolization. [22]

Rare clinical situations in which tumor lysis syndrome has been observed include pregnancy and fever. Patients under general anesthesia have also experienced tumor lysis syndrome.