Chronic lymphocytic leukemia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

Overview

The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy. Asymptomatic chronic lymphocytic leukemia patients are managed with observation and follow-up, whereas symptomatic chronic lymphocytic leukemia patients are treated with immunochemotherapy. Immunochemotherapies used for the treatment of chronic lymphocytic leukemia patients include purine analogues, alkylating agents, monoclonal antibodies, corticosteroids, tyrosine kinase inhibitors, and B-cell receptor pathway inhibitors. Radiation therapy is not recommended for the management of chronic lymphocytic leukemia patients.

Immunochemotherapy

  • The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy.
  • Asymptomatic chronic lymphocytic leukemia patients are managed with observation and follow-up, whereas symptomatic chronic lymphocytic leukemia patients are treated with immunochemotherapy.[1]
  • 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 ≥ one month
  • Unintentional significant weight loss (≥10%) over a period of six months
  • An increase of greater than 50% over a 2-month period
  • A lymphocyte doubling in a period shorter than six months
  • Purine analogues such as:
  • Alkylating agents such as:
  • Monoclonal antibodies such as:
  • Immunomodulatory agents such as:
  • Corticosteroids such as:
  • Tyrosine kinase and B-Cell receptor pathway inhibitors such as:
  • Idelalisib (targets phosphoinositide 3-kinase delta)
  • Ibrutinib (targets bruton tyrosine kinase)
  • The optimal immunochemotherapeutic regimen used for the management of chronic lymphocytic leukemia patients depends on a number of factors which include:
  • The algorithm below summarizes the management approach for chronic lymphocytic leukemia patients:[12][13][14]


 
 
 
 
 
Initial patients evaluation
 
 
 
 
 
 
 
 
 
 
History
Physical examination
Complete blood count
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Staging
 
 
 
 
 
 
Rai Staging System
Binet Staging System
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rai stage 0-2
Binet stage A
 
Rai stage 3-4
Binet stage B-C
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients managed by observation and close follow-up
 
Evaluate patients by Cumulative Index Illness Rating Scale
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fit patients (CIRS <6)
 
Frail patients (CIRS ≥6)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FISH chromosomal analysis
 

Obinutuzumab AND chlorambucil
Ofatumumab AND chlorambucil

Rituximab AND chlorambucil
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunochemotherapeutic regimens for the management of patients without chromosome 17p deletion or chromosome 11q deletion can be found here
 
Immunochemotherapeutic regimens for the management of patients with chromosome 17p deletion can be found here
 
Immunochemotherapeutic regimens for the management of patients with chromosome 11q 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 (or younger than 70 years of age with a poor performance status) include (in order of preference):[15][16][17][18]
  • Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age with a good performance status include (in order of preference):[19][20][21][22][23]

Refractory/Relapsed Therapy

  • Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age (or younger than 70 years of age with a poor performance status) include (in order of preference):[24][25][26]
  • Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age with a good performance status include (in order of preference):[27][28][29]

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):[30][31][32][33][34]

Refractory/Relapsed Therapy

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

Immunochemotherapeutic Regimens for the Management of Patients with Chromosome 11q Deletion

First Line Therapy

  • Preferred immunochemotheraptic regimens for the treatment of such patients who are older than 70 years of age (or younger than 70 years of age with a poor performance status) include (in order of preference):[35]
  • Preferred immunochemotheraptic regimens for the treatment of such patients who are younger than 70 years of age with a good performance status include (in order of preference):[36][37]

Allogeneic stem cell transplantation

  • Allogeneic stem cell transplantation (alloSCT) is the only potentially curative end stage treatment option in chronic lymphocytic leukemia patients.[38]

Supportive Therapy

Opportunistic Infections Prophylaxis

  • Vaccines recommended for chronic lymphocytic leukemia patients include:
  • Other strategies for the prevention of opportunistic infections include:

Autoimmune Cytopenia Prophylaxis

Thromboprophylaxis

  • A daily aspirin dose is recommended among chronic lymphocytic leukemia patients who receive lenalidomide while their platelet count is greater than 50000 per microliter.
  • However, aspirin administration is not needed for such chronic lymphocytic leukemia patients who are already on warfarin.

Radiation Therapy

  • Radiation therapy is not recommended for the management of chronic lymphocytic leukemia patients.

References

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  3. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S (October 2010). "Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial". Lancet. 376 (9747): 1164–74. doi:10.1016/S0140-6736(10)61381-5. PMID 20888994.
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  37. Woyach JA, Ruppert AS, Rai K, Lin TS, Geyer S, Kolitz J, Appelbaum FR, Tallman MS, Belch AR, Morrison VA, Larson RA, Byrd JC (February 2013). "Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential cancer and leukemia group B studies". J. Clin. Oncol. 31 (4): 440–7. doi:10.1200/JCO.2011.41.5646. PMC 3731920. PMID 23233702.
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