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    Chronic Lymphocytic Leukemia Complication

    Hematological / Oncological

    Last Reviewed on Feb 28, 2024
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    By Tarinder Grewal,Jessica Ter Wolbeek

    First 5 Minutes

    When patients with a previous diagnosis of chronic lymphocytic leukemia (CLL) present to the emergency department, the following oncologic emergencies should always be considered:


    • Chronic lymphocytic leukemia (CLL) is a hematological malignancy wherein dysfunctional mature B cells accumulate in the blood and bone marrow.
    • CLL is the most common leukemia in adults, with 70 being the average age at diagnosis and nearly 2000 new cases in Canada each year.
    • A wide range of complications can occur in patients with CLL, many of which can lead to an emergency department presentation including:
      • infection
      • febrile neutropenia
      • tumour lysis syndrome (10% of CLL patients after chemotherapy)
      • autoimmune cytopenias including:
        • autoimmune hemolytic anemia (7-10% of patients with CLL)
        • immune thrombocytopenic purpura (1-5%)
      • Richter transformation (2-10%)
    • CLL complications may be disease-related and/or treatment-related.

    Diagnostic Process

    • It is important to establish whether the patient is on treatment for CLL, which chemotherapy or immunotherapy agent(s) they have received, and the timing of the last treatment.
    • Other history to inquire about includes subjective fever, sick contacts, travel history, respiratory symptoms including cough or dyspnea, diarrhea, nausea, vomiting, urinary symptoms, oliguria, changes in mental status, headache, stiff neck, skin changes including rash, new pain, and increased weight loss and/or night sweats.
    • A complete physical examination is essential with special attention paid to respiratory, skin, mucous membranes (look for evidence of mucositis), lymph nodes, assessment for hepatosplenomegaly, and examination of the perianal area for lesions.
    • Expert opinion recommends avoiding a DRE due to the risk of barrier compromise.
    • Choice of investigations should be driven by clinical suspicion.
    • Tests to consider include ECG, CBC with differential and peripheral smear, electrolytes, extended electrolytes, uric acid, creatinine, urea, liver enzymes, bilirubin, haptoglobin, LDH, lactate, blood cultures, urinalysis, and urine C&S.
    • Additional cultures can be considered if there are any localized infectious findings.
    • A lumbar puncture should be performed if symptoms of meningitis are present.
    • AP and lateral chest x-ray.
    • Febrile neutropenia
      • is defined as an abnormally low neutrophil count (ANC < 0.5×109/L) in conjunction with either:
        • a fever (a single oral temperature of ≥ 38.3°C or ≥ 38°C for more than 1 hour)
        • OR any infectious signs or symptoms.
    • Tumour lysis syndrome
      • is the rapid destruction of malignant cells.
      • hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia.
      • secondary renal failure is common.
      • cardiac arrhythmias also occur.
    • Patients with autoimmune hemolytic anemia (AIHA)
      • often have symptoms of anemia, e.g., fatigue, dyspnea on exertion, palpitations, pallor.
      • likely have low hemoglobin, elevated reticulocytes, low haptoglobin, elevated LDH, and elevated bilirubin.
      • Many CLL patients with warm AIHA have a negative direct antiglobulin test (DAT).
    • Symptoms and signs of immune thrombocytopenic purpura (ITP) include:
      • Fatigue, petechiae, purpura, or epistaxis.
      • platelet levels below 100×109/L.
    • Richter transformation
      • is the sudden conversion of CLL into a more aggressive form of cancer, usually diffuse large B-Cell lymphoma (DLBCL).
      • can be manifested as acute lymphadenopathy, splenomegaly, increased B-symptoms (Fever greater than 38 °C., Drenching sweats, especially at night. Unintentional weight loss of >10% of normal body weight over a period of 6 months or less).
      • can be diagnosed by lymph node biopsy.

    Recommended Treatment

    • Febrile neutropenia
      • treat with broad spectrum antibiotics immediately after blood cultures are drawn
        • piperacillin-tazobactam 4.5g IV q6h.
        • additional antibiotics such as vancomycin or metronidazole may be indicated.
      • continue with infectious workup after antibiotics have been initiated.
    • CLL patients with an infection and ANC > 1×109/L
      • most often the infection is bacterial and can be treated with antibiotics directed at the most likely pathogen, based on the clinical presentation.
      • common pathogens include S. pneumoniae and H. influenzae.
      • active treatment of CLL increases the risk of atypical pathogens such as Mycobacteria, Listeria, Pneumocystis jirovecii, Aspergillus, and Cryptococcus.
      • viral reactivation should be treated with early antiviral therapy.
    • Tumour lysis syndrome
      • cardiac monitoring.
      • urine output.
      • intensive hydration with IV fluids, up to 6L per day.
      • hemodialysis may be indicated.
      • treatment guidelines no longer support alkalinization of the urine.
      • management of hyperkalemia with calcium gluconate, insulin, bicarbonate, beta agonists, and oral potassium binders (Kayexalate – sodium polystyrene); Calcium resonium.
      • oral phosphate binders (Calcium carbonate (tums); Renvela (sevelamer carbonate).
      • hyperuricemia can be managed pharmacologically with allopurinol or rasburicase.
      • patients with cardiac or neurologic signs of hypocalcemia should receive intravenous calcium repletion.
    • AIHA
      • supportive care includes blood transfusion, if indicated by hemoglobin levels, and folic acid supplementation (1mg PO daily).
      • definitive treatment is as for idiopathic autoimmune cytopenia, with most patients responding to corticosteroids.
        • prednisone 1-2 mg/kg PO daily for 2 to 4 weeks and tapered over months.
      • there is good evidence for improved outcomes using combined therapy with rituximab, but optimal dosing is unknown.
    • ITP
      • treatment decisions are based on the presence and severity of bleeding, bleeding risk, and platelet count.
      • first-line treatments include platelet transfusion (for critical bleeding), IVIG, glucocorticoids (usually dexamethasone 40mg IV daily for 4 days).
      • as in AIHA, rituximab has been used with good results but the most effective dosing is not clearly defined.
    • Richter transformation
      • initial treatment should be supportive.
      • patients should be referred to medical oncology for treatment of the new lymphoma.

    Criteria For Hospital Admission

    • Any patient with a hematological malignancy and febrile neutropenia with high risk features.
    • Sepsis.
    • All patients with tumour lysis syndrome should be admitted to hospital.
    • Patients with cardiac, neurological, or kidney manifestations of TLS should be admitted to ICU.
    • Patients with AIHA or ITP requiring transfusion or IV therapies.

    Criteria For Transfer To Another Facility

    • Dependent on local resources.

    Criteria For Close Observation And/or Consult

    • Febrile neutropenia: consult oncology/hematology ± infectious diseases.
    • Tumour lysis syndrome: consult oncology, consider consults to nephrology and palliative care.
    • AIHA and/or ITP: consult oncology ± hematology.
    • Richter transformation: consult oncology.

    Quality Of Evidence?


    Expert opinion.


    Related Information

    Reference List

    1. Rai KR, Stilgenbauer, S. 2022. Overview of the complications of chronic lymphocytic leukemia. UpToDate. Retrieved January 2024 from https://www.uptodate.com/contents/overview-of-the-complications-of-chronic-lymphocytic-leukemia

    2. Dearden C. Disease-specific complications of chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2008:450-6.

    3. Autore F, Pasquale R, Innocenti I, Fresa A, Sora’ F, Laurenti L. Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review. Cancers (Basel). 2021 Nov 19;13(22):5804.

    4. Wacker DA, McCurdy MT. Oncologic Emergencies. In: Walls RM, Hockberger RS, Gausche-Hill M, Erickson TB, Wilcox SR, editors. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 10th ed. Philadelphia (US): Elsevier; 2023. p. 1500-1516.

    5. Higdon ML, Atkinson CJ, Lawrence, KV. Oncologic Emergencies. Am Fam Physician. 2018 97(11):741-748.


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