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 combination immunochemotherapy.[1] Asymptomatic chronic lymphocytic leukemia patients are managed with observation and follow-up, whereas symptomatic chronic lymphocytic leukemia patients are treated with immunochemotherapy. Immunochemotherapies for chronic lymphocytic leukemia include purine analogues, alkylating agents, monoclonal antibodies, steroids, corticosteroids, Tyrosine kinase inhibitors, and B-cell receptor pathway inhibitors.[1][2] Radiation therapy is not recommended for the management of chronic lymphocytic leukemia patients.[3]
Immunochemotherapy
- The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is combination immunochemotherapy.[1]
- Asymptomatic chronic lymphocytic leukemia patients are managed with observation and follow-up, whereas symptomatic chronic lymphocytic leukemia patients are treated with immunochemotherapy.
- Indications to initiate immunochemotherapy among patients with chronic lymphocytic leukemia include:[3]
- 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 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.[1][2]
- 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:[3]
- 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:[1][3][2]
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) | ||||||||||||||||||||||||||||||||||||||||||||
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):[2]
- 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):[2]
- 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):[2]
- 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):[2]
- 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
Supportive Therapy
Infection prophylaxis
- Pneumococcal vaccine administered every five years
- Influenza vaccine administered annually
- Live attenuated vaccines should be avoided among chronic lymphocytic leukemia patients.
- Other strategies for the prevention of opportunistic infections include:
- Sulfamethoxazole/trimethoprim can be administered to patients receiving purine analogues as a prophylaxis for pneumocystis pneumonia infection
- Acyclovir can be administered to patients receiving purine analogues as a prophylaxis for herpes simplex virus infection.
Autoimmune cytopenia prophylaxis
- Corticosteroids is recommended for the management of autoimmune cytopenia among chronic lymphocytic leukemia patients. Other therapeutic measures may include:[2]
- Romiplostim is recommended for the management of autoimmune thrombocytopenia among chronic lymphocytic leukemia patients.
Radiation Therapy
- Radiation therapy is not recommended for the management of chronic lymphocytic leukemia patients.[1][2][3]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 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
- ↑ 3.0 3.1 3.2 3.3 3.4 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.