Sandbox:therapy

• Asymptomatic patients with chronic lymphocytic leukemia are managed with observation, whereas symptomatic patients with chronic lymphocytic leukemia are treated with immunochemotherapy.
• Indications to initiate immunochemotherapy among patients with chronic lymphocytic leukemia include:

• Symptomatic chronic lymphocytic leukemia patients presenting with:

• Fever of unknown origin (>38.1°C for a period greater than two weeks)
• Night sweats for more than one month
• Unintentional significant weight loss over a period of six months

• Patients presenting with thrombocytopenia or anemia due to bone marrow failure
• Patients presenting with refractory autoimmune anemia or refractory autoimmune thrombocytopenia
• Evidence of symptomatic splenomegaly, with the spleen being palpated more than 6cm below the costal margin
• Evidence of symptomatic progressive lymph nodes swelling, with a size greater than 10 cm in diameter
• Evidence of a rapidly progressive lymphocytosis, which may be indicated by:

• An increase of greater than 50% over a 2-month period
• A lymphocyte doubling period shorter than six months

• The optimal therapy for chronic lymphocytic leukemia depends on a number of factors which include:

• The clinical presentation of the patients
• The stage of the tumor
• The presence of specific genetic mutations
• The performance status of the patients
• First line therapy vs. second line therapy

• The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is combination immunochemotherapy.
• Immunochemotherapies for chronic lymphocytic leukemia include purine analogues, alkylating agents, monoclonal antibodies, Tyrosine kinase and B-Cell receptor pathway inhibitors.
• Purine analogues used for the management of chronic lymphocytic leukemia patines may include:

• Cladribine
• Fludarabine
• Pentostatin

• Alkylating agents used for the management of chronic lymphocytic leukemia patients may include:

• Bendamustine
• Chlorambucil
• Cyclophosphamide

• Monoclonal antibodies used for the management of chronic lymphocytic leukemia patients may include:

• Rituximab (anti-CD20)
• Ofatumumab (anti-CD20)
• Obinutuzumab (anti-CD20)
• Alemtuzumab (anti-CD52)

• Immunomodulatory agents used for the management of chronic lymphocytic leukemia patients may include:

• Lenalidomide

• Tyrosine kinase and B-Cell receptor pathway inhibitors used for the management of chronic lymphocytic leukemia patients may include:

• Idelalisib (targets phosphoinositide 3-kinase delta)
• Ibrutinib (targets bruton tyrosine kinase)