Sandbox:therapy

# Immunochemotherapy
- The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is combination immunochemotherapy.
- 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 (>38.1C 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 hemolytic 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
- Immunochemotherapies for chronic lymphocytic leukemia include purine analogues, alkylating agents, monoclonal antibodies, steroids, corticosteroids, Tyrosine kinase inhibitors, 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
- Corticosteroids used for the management of chronic lymphocytic leukemia patients may include:
- Methylprednisolone
- Prednisone
- 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. refractory/relapsed therapy
- The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:

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

### First line therapy
- Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age include (in order of preference):
- Obinutuzumab AND chlorambucil
- Ofatumumab AND chlorambucil
- Rituximab AND chlorambucil
- Bendamustine  rituximab
- Obinutuzumab
- Fludarabine  rituximab
- Chlorambucil
- Rituximab
- Cladribine
- Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age include (in order of preference):
- Fludarabine AND cyclophosphamide AND rituximab
- Fludarabine AND rituximab
- Pentostatin AND cyclophosphamide AND rituximab
- Bendamustine AND rituximab

### Refractory/relapsed therapy
- Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age include (in order of preference):
- Ibrutinib
- Idelalisib  rituximab
- Fludarabine AND cyclophosphamide AND rituximab (reduced dose)
- Pentostatin AND cyclophosphamide AND rituximab (reduced dose)
- Bendamustine  rituximab
- High-dose methylprednisolone AND rituximab
- Ofatumumab
- Obinutuzumab
- Lenalidomide  rituximab
- Alemtuzumab  rituximab
- Dose-dense rituximab
- Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age include (in order of preference):
- Ibrutinib
- Idelalisib  rituximab
- Fludarabine AND cyclophosphamide AND rituximab
- Pentostatin AND cyclophosphamide AND rituximab
- Bendamustine  rituximab
- Fludarabine AND alemtuzumab
- Rituximab AND cyclophosphamide AND doxorubicin AND vincristine AND cytarabine
- Oxaliplatin AND fludarabine AND cytarabine AND rituximab
- Ofatumumab
- Obinutuzumab
- Lenalidomide  rituximab
- Alemtuzumab  rituximab
- High-dose methylprednisolone AND rituximab

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

### First line therapy
- Preferred immunochemotheraptic regimens for the treatment of such patients regardless the age group include (in order of preference):
- Ibrutinib
- High-dose methylprednisolone AND rituximab
- Fludarabine AND rituximab
- Fludarabine AND cyclophosphamide AND rituximab
- Obinutuzumab AND chlorambucil
- Alemtuzumab  rituximab
- Rituximab AND chlorambucil

### Refractory/relapsed therapy
- Preferred immunochemotheraptic regimens for the treatment of such patients regardless the age group include (in order of preference):
- Ibrutinib
- Idelalisib  rituximab
- High-dose methylprednisolone AND rituximab
- Lenalidomide  rituximab
- Ofatumumab
- Oxaliplatin AND fludarabine AND cytarabine AND rituximab

## Immunochemotherapeutic regimens for management of patients with chromosome 11q deletion

### First line therapy
- Preferred immunochemotheraptic regimens for the treatment such patients who are older than 70 years of age include (in order of preference):
- Obinutuzumab AND chlorambucil
- Ofatumumab AND chlorambucil
- Rituximab AND chlorambucil
- Bendamustine  rituximab
- Cyclophosphamide AND prednisone  rituximab
- Fludarabine AND cyclophosphamide AND rituximab (reduced dose)
- Rituximab
- Preferred immunochemotheraptic regimens for the treatment such patients who are younger than 70 years of age include (in order of preference):
- Fludarabine AND cyclophosphamide AND rituximab
- Bendamustine  rituximab
- Pentostatin AND cyclophosphamide AND rituximab
- Obinutuzumab AND chlorambucil
-  Jump up to: 1.0 1.1 1.2 Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 226576. doi:10.1001/jama.2014.14553. PMID 25461996..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
-  Jump up to: 2.0 2.1 2.2 Hallek M (2015). "Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment". Am J Hematol. 90 (5): 44660. doi:10.1002/ajh.23979. PMID 25908509.
-  Jump up to: 3.0 3.1 3.2 3.3 3.4 3.5 NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015)  Accessed on October, 15 2015