Chronic lymphocytic leukemia (CLL) is a malignant, chronic lymphoproliferative disorder characterized by proliferation and accumulation of monoclonal B-cells in the bone marrow, peripheral blood, lymph nodes, liver and spleen.

It is the most common form of adult leukemia in the Western world but rare in Asians.

Exact etiology is unknown but usually associated with genetic aberrations and lesions.


Supportive Therapy

Autoimmune Cytopenias
  • Immune thrombocytopenic purpura is associated with poorer survival in chronic lymphocytic leukemia (CLL) patients
  • Treatment includes administration of corticosteroids; splenectomy, Rituximab, intravenous immunoglobulin (IVIG), or Cyclosporin may be considered for patients unresponsive to corticosteroid therapy
    • Romiplostim, & Eltrombopag may also be considered for patients unresponsive to splenectomy, steroids & intravenous immunoglobulin


  • Prevention of infectious complications by administration of intravenous immunoglobulin, anti-infective prophylaxis, & vaccinations are recommended
    • Annual influenza vaccination & S pneumoniae vaccine every 5 years is recommended
    • Immunoglobulin replacement therapy may be considered for patients with recurrent, severe infection despite prophylactic antibiotic therapy
    • Hepatitis B virus & Pneumocystis pneumonia prophylaxis with Acyclovir & Sulfamethoxazole/Trimethoprim respectively, are recommended for high-risk patients receiving anti-CD20 monoclonal antibodies & Alemtuzumab

Cytomegalovirus (CMV) reactivation

  • Occurs in 10-25% of patients undergoing treatment with Alemtuzumab
  • Prophylaxis with Ganciclovir may be considered in patients with increasing viral load during treatment
  • Quantitative PCR should be conducted every 2-3 weeks to measure cytomegalovirus (CMV) viremia

Hepatitis B Virus

  • Increased risk for hepatitis B virus reactivation in patients undergoing treatment with anti-CD20 monoclonal antibody
  • Prophylaxis with Entecavir is recommended for patients on immunosuppressive cytotoxic therapy with positive Hepatitis B surface antigen (HBsAg), HBsAg negative but Hepatitis B core antibody (HBcAb) positive, or elevated HBsAb levels with increasing HBV DNA load
    • Studies show that Lamivudine is an effective prophylactic option but with high incidence for resistance development
    • Adenofir, Telbivudine, & Tenofovir are options for patients unresponsive to Lamivudine therapy
  • Viral load should be monitored using polymerase chain reaction (PCR) monthly during & every 3 months after treatment
  • Prophylactic regimen should be continued until 12 months after treatment

Richter’s Transformation

  • Histologic transformation of chronic lymphocytic leukemia to a more aggressive form of lymphoma, diffuse large B-cell lymphoma (DLBCL)
  • Chemoimmunotherapeutic regimens such as OFAR (Oxaliplatin, Fludarabine, Cytarabine, Rituximab), hyper-CVAD (Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone alternating with high-dose Methotrexate & Cytarabine) with Rituximab, DA-EPOCH-R (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin w/ Rituximab), & RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) may be given
  • Hematopoietic stem cell transplatation may also be considered for chemotherapy-sensitive transformed chronic lymphocytic leukemia

Tumor Flare Reaction

  • An immune response composed of splenomegaly, fever, rashes, painful lymphadenopathy, lymphocytosis & bone pain
  • Commonly occurs in patients given immunomodulating agents (eg Lenalidomide) & kinase inhibitors (eg Ibrutinib, Idelalisib)
  • Corticosteroid administration is recommended for management of inflammation & lymphadenopathy
    • Prophylaxis with steroids may be considered for patients with bulky lymph nodes prior to initiation of Lenalidomide treatment
  • Antihistamines may be used to manage pruritus with rashes

Tumor Lysis Syndrome

  • Cellular destruction secondary to chemotherapy causing severe lymphadenopathy, hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, which may lead to acute renal failure
  • Prophylaxis prior to chemotherapy (especially w/ Lenalidomide, Obinutuzumab, Venetoclax, & chemoimmunotherapeutic agents) is recommended
    • May give Allopurinol for patients w/ low-to high-risk, or Febuxostat for patients at high-risk, 2-3 days prior to initiation of chemotherapy then continued for 10-14 days
    • Rasburicase is recommended for patients with any high-risk features, urgent need for treatment initiation, when unable to achieve adequate hydration & for patients with acute renal failure
  • Known to cause acute renal failure, cardiac arrhythmias, seizures, paralysis & eventually death if left untreated

Venous Thromboembolism

  • Associated w/ Lenalidomide use in chronic lymphocytic leukemia patients
  • Prophylaxis w/ Aspirin therapy for patients w/ platelet count ≥50 x 1012/L is recommended
    • Not recommended for patients currently undergoing anticoagulant therapy (eg Warfarin)
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