27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity

Structural Oncologic Emergencies

Superior Vena Cava Syndrome

• Causes: lung cancer (especially small cell), lymphoma, germ cell tumors, and increasingly indwelling catheters and pacemaker leads causing thrombosis.
• Presentation: facial and upper extremity swelling, distended neck and chest veins, plethora, cough, and dyspnea worsened by lying flat. Stridor, severe dyspnea at rest, and altered mental status from cerebral edema mark true emergencies.
• Management:
  • Elevate the head, give oxygen.
  • Establish the diagnosis before treating when the patient is stable, because treatment depends on tumor type: obtain tissue, since lymphoma and germ cell tumors respond rapidly to chemotherapy.
  • Endovascular stenting provides the fastest relief and is favored for severe symptoms.
  • Radiotherapy for radiosensitive tumors; anticoagulation and catheter removal for catheter-associated thrombosis.
  • Corticosteroids help in lymphoma and with airway edema, but can obscure a lymphoma diagnosis if given before biopsy.

Malignant Spinal Cord Compression

• Presentation: back pain that precedes neurologic signs (often worse when recumbent or with Valsalva), then weakness, sensory level, and finally bladder and bowel dysfunction. Breast, lung, prostate, myeloma, and lymphoma are the common primaries.
• Management:
  1. Dexamethasone immediately (commonly 10 mg IV, then 4 mg every 6 hours; higher loading doses are used in severe deficits).
  2. Urgent MRI of the whole spine, because multiple levels are common.
  3. Surgical decompression and stabilization in suitable candidates, particularly with spinal instability, a single level, or radioresistant tumor; otherwise radiotherapy. Function at the time of treatment is the strongest predictor of recovery, so hours matter.
• Cauda equina syndrome from malignancy follows the same urgent pathway.

Hyperviscosity Syndrome

• Causes: Waldenström macroglobulinemia (IgM), multiple myeloma (especially IgA), and extreme leukocytosis or polycythemia.
• Features: mucosal bleeding (epistaxis, gingival bleeding), visual changes with "sausage-link" retinal veins, headache, confusion, and heart failure.
• Treatment: urgent plasmapheresis for paraprotein-driven disease, then treat the underlying malignancy. Avoid red cell transfusion before viscosity is reduced.

Tumor Lysis Syndrome

Covered in the electrolyte section: hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia with acute kidney injury. Prevention uses hydration plus allopurinol, with rasburicase for high-risk patients (contraindicated in G6PD deficiency because it causes hemolysis, and samples must be kept on ice to avoid falsely low uric acid readings).

Hypercalcemia of Malignancy

• Mechanisms: parathyroid hormone-related peptide (squamous cancers, kidney, breast), osteolytic metastases, and calcitriol production in lymphoma.
• Treatment:
  • Isotonic saline to restore volume and calciuresis.
  • Calcitonin (4 units/kg every 12 hours) for rapid but transient lowering over the first 48 hours, after which tachyphylaxis develops.
  • Zoledronic acid (adjusted for kidney function) or denosumab (useful in kidney impairment and bisphosphonate failure) for durable control.
  • Glucocorticoids for calcitriol-mediated hypercalcemia in lymphoma and granulomatous disease.
  • Dialysis for severe hypercalcemia with kidney failure.
  • Loop diuretics are no longer routine; they are used only to manage volume overload.

Other Oncologic Emergencies

• Malignant pericardial effusion and tamponade: drainage with a pericardial window or catheter; sclerosis or intrapericardial therapy for recurrence.
• Malignant airway obstruction: stenting, laser, or radiotherapy; heliox as a bridge.
• Massive hemoptysis and gastrointestinal bleeding from tumor: embolization or radiotherapy.
• Adrenal insufficiency from metastases or checkpoint inhibitor hypophysitis.
• SIADH from small cell lung cancer.
• Thrombosis from Trousseau syndrome.
• Bowel obstruction or perforation, including after bevacizumab, and neutropenic enterocolitis.

Hematopoietic Cell Transplant Complications

ICU admission for transplant recipients no longer carries the futility once assumed; early admission and noninvasive support strategies, with clear goals, improve outcomes.

Cellular and Immune Therapy Toxicity

Cytokine Release Syndrome (CRS)

• Timing: hours to days after CAR-T cell infusion or bispecific T-cell engager therapy.
• Grading (ASTCT) is based on fever plus hypotension and hypoxemia:
  • Grade 1: fever alone.
  • Grade 2: hypotension not requiring vasopressors, or hypoxemia needing low-flow oxygen.
  • Grade 3: hypotension requiring one vasopressor, or hypoxemia requiring high-flow oxygen or noninvasive ventilation.
  • Grade 4: multiple vasopressors or positive-pressure ventilation.
• Treatment: supportive care and tocilizumab (an IL-6 receptor antagonist) for grade 2 or higher, with corticosteroids added for higher grades or inadequate response; anakinra and other agents for refractory cases. Rule out concurrent infection, which looks identical, and treat empirically.
• Related syndromes: ICANS (see the encephalopathy section), prolonged cytopenias, hypogammaglobulinemia, and hemophagocytic lymphohistiocytosis-like toxicity.

Immune Checkpoint Inhibitor Toxicity

Severe (grade 3 or 4) immune-related adverse events are an ICU problem:

• Myocarditis (high mortality; see the myocarditis section): high-dose methylprednisolone, escalate to abatacept or antithymocyte globulin.
• Pneumonitis: stop the drug, methylprednisolone 1 to 2 mg/kg, add infliximab or mycophenolate if no improvement in 48 hours.
• Colitis: steroids, then infliximab or vedolizumab; exclude infection and CMV.
• Hepatitis: steroids; avoid infliximab, use mycophenolate.
• Hypophysitis and adrenalitis: hormone replacement with hydrocortisone before levothyroxine.
• Diabetes with ketoacidosis: insulin; the beta cell loss is permanent.
• Myasthenia-like syndrome, Guillain-Barré-like neuropathy, and encephalitis: steroids plus IVIG or plasma exchange.
• General principle: hold the checkpoint inhibitor, give corticosteroids early for grade 3 or 4 toxicity, and add a second-line immunosuppressant if there is no response within 48 to 72 hours. Steroids do not blunt antitumor efficacy enough to justify withholding them in severe toxicity.