Chronic%20lymphocytic%20leukemia Treatment

• Most common forms in chronic lymphocytic leukemia (CLL) patients include autoimmune hemolytic anemia, immune-mediated thrombocytopenia (also known as immune thrombocytopenic purpura) and pure red blood cell aplasia 
• Immune thrombocytopenic purpura is associated with poorer survival in CLL patients
• Treatment includes administration of corticosteroids; splenectomy, Rituximab, intravenous immunoglobulin (IVIg), or Cyclosporin may be considered for patients unresponsive to corticosteroid therapy
  • Romiplostim and Eltrombopag may also be considered for patients unresponsive to splenectomy, steroids and intravenous immunoglobulin

Infection/Reactivation

• Prevention of infectious complications by administration of intravenous immunoglobulin, anti-infective prophylaxis, and vaccinations are recommended
  • Annual influenza vaccination (except live vaccines) and pneumococcal polysaccharide vaccine (PPSV23) every 5 years is recommended
  • Recombinant adjuvanted zoster vaccine is recommended for treatment-naive patients or those given Bruton's tyrosine kinase inhibitor therapy
  • Coronavirus disease 2019 (COVID-19) vaccine for all CLL patients
  • Immunoglobulin replacement therapy (monthly subcutaneous or IVIg) may be considered for patients with recurrent, severe infection despite prophylactic antibiotic therapy
  • Herpes virus and Pneumocystis pneumonia prophylaxis with Acyclovir and Sulfamethoxazole/Trimethoprim respectively, are recommended for high-risk patients receiving Duvelisib or Idelalisib, purine analog or Bendamustine-based chemoimmunotherapy and/or Alemtuzumab

Cytomegalovirus (CMV) Reactivation

• Increased risk of reactivation in patients receiving Alemtuzumab, Idelalisib or Fludarabine-based chemoimmunotherapy
• 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 (HBV)

• Increased risk for hepatitis B virus reactivation in patients undergoing treatment with anti-CD20 monoclonal antibody, Alemtuzumab, Ibrutinib and Idelalisib
• 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 hepatitis B surface antibody (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, and Tenofovir are options for patients unresponsive to Lamivudine therapy
• Viral load should be monitored using polymerase chain reaction (PCR) monthly during and every 3 months after treatment
• Prophylactic regimen should be continued until 12 months after treatment

Richter’s Transformation

• Histologic transformation of CLL to a more aggressive form of lymphoma such as diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL)
• Chemoimmunotherapeutic regimens such as OFAR (Oxaliplatin, Fludarabine, Cytarabine, Rituximab), hyper-CVAD (Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone alternating with high-dose Methotrexate and Cytarabine) with Rituximab, DA-EPOCH-R (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin with Rituximab), and RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) may be given
  • For patients with history of 1 full dose of Rituximab IV therapy, SC Rituximab plus human recombinant hyaluronidase may be used
  • For chemotherapy-refractory or del(17p)/TP53 mutation patients who are unable to receive chemoimmunotherapy, treatment options include Nivolumab with or without Ibrutinib, or Pembrolizumab with or without Ibrutinib
• Hematopoietic cell transplantation may also be considered for chemotherapy-sensitive transformed CLL

Tumor Flare Reactions

• An immune response composed of splenomegaly, fever, rashes, painful lymphadenopathy, lymphocytosis and bone pain
• Commonly occurs in patients given immunomodulating agents (eg Lenalidomide) and kinase inhibitors (eg Ibrutinib, Idelalisib)
• Corticosteroid administration is recommended for management of inflammation and 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 with Lenalidomide, Obinutuzumab, Venetoclax, and chemoimmunotherapeutic agents) is recommended
  • May give Allopurinol for patients with 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 and for patients with acute renal failure
• Known to cause acute renal failure, cardiac arrhythmias, seizures, paralysis and eventually death if left untreated

Venous Thromboembolism

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