Sandbox:therapy

• Asymptomatic chronic lymphocytic leukemia patients are managed with observation, whereas symptomatic chronic lymphocytic leukemia patients 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 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
• Ofatumumab
• Obinutuzumab
• Alemtuzumab

• 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)

• The optimal immunochemotherapeutic regimens used for the management of chronic lymphocytic leukemia depends on a number of factors which include:

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

• The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:

Initial patients evaluation

History Physical examination Complete blood count

Staging

Rai Staging System Binet Staging System

Rai stage 3-4 Binet stage B-C

Rai stage 0-2 Binet stage A

Evaluate patients by cumulative index illness rating scale

Patients managed by observation and close follow-up

Frail patients (CIRS ≥6)

Fit patients (CIRS <6)

Retixumab/obinutuzumab AND chlorambucil

FISH chromosomal analysis

Immunochemotherapeutic regimens for management of patients without chromosome 17p deletion or chromosome 11q deletion can be found here

Immunochemotherapeutic regimens for management of patients with chromosome 17p deletion can be found here

Immunochemotherapeutic regimens for management of patients with chromosome 17p deletion can be found here

Immunochemotherapeutic regimens for the management of patients without chromosome 17p deletion or chromosome 11q deletion

Bendamustine + Rituximab

Chlorambucil

Chlorambucil + PredniSONE

Cladribine

Cyclophosphamide/PredniSONE

Cyclophosphamide/PredniSONE + Rituximab

FCR (Fludarabine/Cyclophosphamide + Rituximab)

Fludarabine

FR (Fludarabine + Rituximab)

MethylPREDNISolone (Pulse)

PCR (Pentostatin/Cyclophosphamide + Rituximab)

Rituximab

Immunochemotherapeutic regimens for the management of patients with chromosome 17p deletion

Alemtuzumab + Rituximab

Bendamustine + Rituximab

FCR (Fludarabine/Cyclophosphamide + Rituximab)

FR (Fludarabine + Rituximab)

HDMP (High-Dose Methylprednisolone) + Rituximab

Immunochemotherapeutic regimens for management of patients with chromosome 11q deletion

Bendamustine + Rituximab

Chlorambucil

Chlorambucil + PredniSONE

Cyclophosphamide/PredniSONE

Cyclophosphamide/PredniSONE + Rituximab

FCR (Fludarabine/Cyclophosphamide + Rituximab)

PCR (Pentostatin/Cyclophosphamide + Rituximab)

Reduced-dose FCR (Fludarabine/Cyclophosphamide + Rituximab)

Rituximab