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* '''Asymptomatic''' chronic lymphocytic leukemia  patients are managed with observation, whereas '''symptomatic''' chronic lymphocytic leukemia  patients are treated with immunochemotherapy.
==Immunochemotherapy==
* Indications to initiate immunochemotherapy among patients with chronic lymphocytic leukemia include:
* The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is combination immunochemotherapy.<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996  }} </ref>
:* Symptomatic chronic lymphocytic leukemia patients presenting with:
* '''[[Asymptomatic]]''' chronic lymphocytic leukemia  patients are managed with observation, whereas '''[[symptomatic]]''' chronic lymphocytic leukemia  patients are treated with immunochemotherapy.
::* Fever of unknown origin (>38.1°C for a period greater than two weeks)
* Indications to initiate immunochemotherapy among patients with chronic lymphocytic leukemia include:<ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509  }} </ref>
::* Night sweats for more than one month
:* [[Symptomatic]] chronic lymphocytic leukemia patients presenting with:
::* Unintentional significant weight loss over a period of six months
::* [[Fever]] of unknown origin (>38.1°C for a period greater than two weeks)
:* Patients presenting with [[thrombocytopenia]] or anemia due to bone marrow failure
::* [[Night sweats]] for more than one month
:* Patients presenting with refractory autoimmune anemia or refractory autoimmune thrombocytopenia
::* Unintentional significant [[weight loss]] over a period of six months
:* Evidence of symptomatic splenomegaly, with the spleen being palpated more than 6cm below the costal margin
:* Patients presenting with [[thrombocytopenia]] or [[anemia]] due to [[bone marrow failure]]
:* Evidence of symptomatic progressive lymph nodes swelling, with a size greater than 10 cm in diameter
:* Patients presenting with refractory [[autoimmune hemolytic anemia]] or refractory [[autoimmune]] [[thrombocytopenia]]
:* Evidence of a rapidly progressive lymphocytosis, which may be indicated by:
:* Evidence of symptomatic [[splenomegaly]], with the [[spleen]] being palpated more than 6cm below the [[costal margin]]
:* Evidence of symptomatic progressive [[lymph node]]s 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
::* An increase of greater than 50% over a 2-month period
::* A lymphocyte doubling period shorter than six months  
::* 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 agent]]s, [[monoclonal antibodies]], [[steroids]], [[corticosteroids]], [[Tyrosine kinase]] inhibitors, and [[B-cell]] [[receptor]] pathway inhibitors.<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996  }} </ref><ref name="NCCN">NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015</ref>
* 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:
:* '''Purine analogues''' used for the management of chronic lymphocytic leukemia patines may include:
::* Cladribine  
::* [[Cladribine]]
::* Fludarabine
::* [[Fludarabine]]
::* Pentostatin
::* [[Pentostatin]]
:* '''Alkylating agents''' used for the management of chronic lymphocytic leukemia patients may include:  
:* '''Alkylating agents''' used for the management of chronic lymphocytic leukemia patients may include:  
::* Bendamustine
::* [[Bendamustine]]
::* Chlorambucil
::* [[Chlorambucil]]
::* Cyclophosphamide
::* [[Cyclophosphamide]]
:* '''Monoclonal antibodies''' used for the management of chronic lymphocytic leukemia patients may include:  
:* '''Monoclonal antibodies''' used for the management of chronic lymphocytic leukemia patients may include:  
::* Rituximab  
::* [[Rituximab]]
::* Ofatumumab  
::* [[Ofatumumab]]
::* Obinutuzumab  
::* [[Obinutuzumab]]
::* Alemtuzumab  
::* [[Alemtuzumab]]
:* '''Immunomodulatory agents''' used for the management of chronic lymphocytic leukemia patients may include:  
:* '''Immunomodulatory agents''' used for the management of chronic lymphocytic leukemia patients may include:  
::* Lenalidomide
::* [[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:  
:* '''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)
::* [[Idelalisib]] (targets phosphoinositide 3-kinase delta)
::* Ibrutinib (targets bruton tyrosine kinase)
::* [[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 optimal immunochemotherapeutic regimens used for the management of chronic lymphocytic leukemia depends on a number of factors which include:<ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509  }} </ref>
:* The clinical presentation of the patients
:* The clinical presentation of the patients
:* The performance status of the patients
:* The [[performance status]] of the patients
:* The stage of the tumor
:* The stage of the [[tumor]]
:* The presence of specific genetic mutations
:* The presence of specific [[genetic mutation]]s
:* First line therapy vs. recurrent/refractory therapy
:* First line therapy vs. refractory/relapsed therapy
 
*The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996  }} </ref><ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509  }} </ref><ref name="NCCN">NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015</ref>
*The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:
<br>
<br>
{{familytree/start |summary=PE diagnosis Algorithm.}}
{{familytree/start |summary=PE diagnosis Algorithm.}}
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<br>
<br>
===Immunochemotherapeutic regimens for the management of patients without chromosome 17p deletion or chromosome 11q deletion===
===Immunochemotherapeutic regimens for the management of patients without chromosome 17p deletion or chromosome 11q deletion===
Bendamustine + Rituximab
Chlorambucil
Chlorambucil + PredniSONE
Cladribine


Cyclophosphamide/PredniSONE
====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'''):<ref name="NCCN">NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015</ref>
:* [[Obinutuzumab]] {{and}} [[chlorambucil]]
:* [[Ofatumumab]] {{and}} chlorambucil
:* [[Rituximab]] {{and}} chlorambucil
:* [[Bendamustine]] {{withorwithout}} rituximab
:* [[Obinutuzumab]]
:* [[Fludarabine]] {{withorwithout}} [[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


Cyclophosphamide/PredniSONE + 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'''):<ref name="NCCN">NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015</ref>
FCR (Fludarabine/Cyclophosphamide + Rituximab)
:* [[Ibrutinib]]
 
:* [[Idelalisib]] {{withorwithout}} [[rituximab]]
Fludarabine
:* [[Fludarabine]] {{and}} [[cyclophosphamide]] {{and}} rituximab (reduced dose)
 
:* [[Pentostatin]] {{and}} cyclophosphamide {{and}} rituximab (reduced dose)
FR (Fludarabine + Rituximab)
:* [[Bendamustine]] {{withorwithout}} rituximab
 
:* High-dose [[methylprednisolone]] {{and}} rituximab
MethylPREDNISolone (Pulse)
:* [[Ofatumumab]]
 
:* [[Obinutuzumab]]
PCR (Pentostatin/Cyclophosphamide + Rituximab)
:* [[Lenalidomide]] {{withorwithout}} rituximab
 
:* [[Alemtuzumab]] {{withorwithout}} rituximab
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]] {{withorwithout}} [[rituximab]]
:* [[Fludarabine]] {{and}} [[cyclophosphamide]] {{and}} [[rituximab]]
:* [[Pentostatin]] {{and}} cyclophosphamide {{and}} rituximab
:* [[Bendamustine]] {{withorwithout}} rituximab
:* [[Fludarabine]] {{and}} [[alemtuzumab]]
:* Rituximab {{and}} cyclophosphamide {{and}} [[doxorubicin]] {{and}} [[vincristine]] {{and}} [[cytarabine]]
:* [[Oxaliplatin]] {{and}} [[fludarabine]] {{and}} [[cytarabine]] {{and}} rituximab
:* [[Ofatumumab]]
:* [[Obinutuzumab]]
:* [[Lenalidomide]] {{withorwithout}} rituximab
:* [[Alemtuzumab]] {{withorwithout}} rituximab
:* High-dose [[methylprednisolone]] {{and}} rituximab


===Immunochemotherapeutic regimens for the management of patients with chromosome 17p deletion===
===Immunochemotherapeutic regimens for the management of patients with chromosome 17p deletion===
Alemtuzumab + Rituximab
====First line therapy====
 
* Preferred immunochemotheraptic regimens for the treatment of such patients regardless the age group include ('''in order of preference'''):<ref name="NCCN">NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015</ref>
Bendamustine + Rituximab
:* [[Ibrutinib]]
 
:* High-dose [[methylprednisolone]] {{and}} [[rituximab]]
FCR (Fludarabine/Cyclophosphamide + Rituximab)
:* [[Fludarabine]] {{and}} rituximab
 
:* Fludarabine {{and}} cyclophosphamide {{and}} rituximab
FR (Fludarabine + Rituximab)
:* [[Obinutuzumab]] {{and}} [[chlorambucil]]
 
:* [[Alemtuzumab]] {{withorwithout}} [[rituximab]]
HDMP (High-Dose Methylprednisolone) + 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 {{withorwithout}} [[rituximab]]
:* High-dose [[methylprednisolone]] {{and}} rituximab
:* [[Lenalidomide]] {{withorwithout}} rituximab
:* [[Ofatumumab]]
:* [[Oxaliplatin]] {{and}} [[fludarabine]] {{and}} [[cytarabine]] {{and}} rituximab


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


Bendamustine + Rituximab
====First line therapy====
 
* Preferred immunochemotheraptic regimens for the treatment such patients who are '''older than 70 years''' of age include (in order of preference):<ref name="NCCN">NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015</ref>
Chlorambucil
:* [[Obinutuzumab]] {{and}} chlorambucil
 
:* [[Ofatumumab]] {{and}} chlorambucil
Chlorambucil + PredniSONE
:* [[Rituximab]] {{and}} [[chlorambucil]]
 
:* [[Bendamustine]] {{withorwithout}} [[rituximab]]
Cyclophosphamide/PredniSONE
:* [[Cyclophosphamide]] {{and}} [[prednisone]] {{withorwithout}} rituximab
 
:* [[Fludarabine]] {{and}} cyclophosphamide {{and}} rituximab (reduced dose)
Cyclophosphamide/PredniSONE + Rituximab
:* Rituximab  
 
FCR (Fludarabine/Cyclophosphamide + Rituximab)
 
PCR (Pentostatin/Cyclophosphamide + Rituximab)
 
Reduced-dose FCR (Fludarabine/Cyclophosphamide + Rituximab)


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]] {{withorwithout}} [[rituximab]]
:* [[Pentostatin]] {{and}} cyclophosphamide {{and}} rituximab
:* [[Obinutuzumab]] {{and}} [[chlorambucil]]

Latest revision as of 22:09, 16 October 2015

Immunochemotherapy

  • The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is combination immunochemotherapy.[1]
  • 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:[2]
  • 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
  • An increase of greater than 50% over a 2-month period
  • A lymphocyte doubling period shorter than six months
  • Purine analogues used for the management of chronic lymphocytic leukemia patines may include:
  • Alkylating agents used for the management of chronic lymphocytic leukemia patients may include:
  • Monoclonal antibodies used for the management of chronic lymphocytic leukemia patients may include:
  • Immunomodulatory agents used for the management of chronic lymphocytic leukemia patients may include:
  • Corticosteroids used for the management of chronic lymphocytic leukemia patients may include:
  • 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:[2]
  • The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:[1][2][3]


 
 
 
 
 
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

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):[3]
  • Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age include (in order of preference):

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):[3]
  • Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age include (in order of preference):

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):[3]

Refractory/relapsed therapy

  • Preferred immunochemotheraptic regimens for the treatment of such patients regardless the age group include (in order of preference):

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):[3]
  • Preferred immunochemotheraptic regimens for the treatment such patients who are younger than 70 years of age include (in order of preference):
  1. ↑ 1.0 1.1 1.2 Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
  2. ↑ 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): 446–60. doi:10.1002/ajh.23979. PMID 25908509.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 NCCN Guidelines Version 2.2015 CLL/SLL. National Comprehensive Cancer Network. (2015) http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf Accessed on October, 15 2015
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