Chronic lymphocytic leukemia overview

# Overview
Chronic lymphocytic leukemia arises from pre-follicular, center B cells, which are normally involved in the process of human immunoglobulins production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis, characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleolus, and the presence of smudge cells. The first comprehensive clinical report of chronic lymphocytic leukemia was published in 1924 by Dr. George Minot, an American physician. Chronic lymphocytic leukemia must be differentiated from other diseases that cause weight loss,  night sweats, hepatosplenomegaly, and palpable lymph nodes, such as hairy cell leukaemia, prolymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.  The most potent risk factor in the development of chronic lymphocytic leukemia is advanced age. Other risk factors include male gender, positive family history, and exposure to certain chemicals. The majority of patients with chronic lymphocytic leukemia are asymptomatic at the time of diagnosis. If left untreated, patients with chronic lymphocytic leukemia may progress to develop weight loss, fever, and lymphadenopathy. Common complications of chronic lymphocytic leukemia include immunodeficiency, warm autoimmune hemolytic anemia, and Richter's transformation. Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is approximately 81.7%. Physical examination of patients with chronic lymphocytic leukemia is usually remarkable for skin pallor, palpable cervical lymph nodes, and hepatomegaly. Laboratory findings consistent with the diagnosis of chronic lymphocytic leukemia include abnormal complete blood count, immunohistochemistry, and electrophoresis. Monoclonality of kappa and lambda producing B cells is a key diagnostic feature among patients with chronic lymphocytic leukemia. According to the Rai Staging System, there are five stages of chronic lymphocytic leukemia based on the degree of lymphocytosis, hemoglobin concentration, platelets concentration, presence of splenomegaly, and presence of lymphadenopathy. While according to the Binet Staging System, there are three stages of chronic lymphocytic leukemia based on the degree of lymphocytosis, the presence of anemia or thrombocytopenia, and the involvement of three or more lymph node regions. Bone marrow biopsy and lymph node biopsy may be helpful in the diagnosis of chronic lymphocytic leukemia. Karyotyping and fluorescent in situ hybridization detect any chromosomal mutations involved in the development of chronic lymphocytic leukemia. The tumor stage is considered one of the important factors that determine the optimal management protocol of chronic lymphocytic leukemia patients. The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy.

# Historical Perspective
The first comprehensive clinical report of chronic lymphocytic leukemia was published in 1924 by Dr. George Minot, an American physician.

# Classification
There is no classification system established for chronic lymphocytic leukemia. Staging systems for chronic lymphocytic leukemia can be viewed here.

# Pathophysiolog,y
Chronic lymphocytic leukemia arises from pre-follicular, center B cells, that are normally involved in the process of human immunoglobulins production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis, characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleolus, and the presence of smudge cells.

# Causes
There are no established direct causes for chronic lymphocytic leukemia. Common genetic mutations involved in the development of chronic lymphocytic leukemia can be found here.

# Differentiating Chronic Lymphocytic Leukemia from other Diseases
Chronic lymphocytic leukemia must be differentiated from other diseases that cause weight loss,  night sweats, hepatosplenomegaly, and palpable lymph nodes, such as hairy cell leukaemia, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.

# Epidemiology and Demographics
In 2011, the age-adjusted incidence of chronic lymphocytic leukemia was 4.82 per 100,000 individuals in the United States. Chronic lymphocytic leukemia is a disease of the elderly and is rarely encountered in individuals under the age of 40. The majority of patients who are newly diagnosed with chronic lymphocytic leukemia are over the age 50 years. Males are more commonly affected with chronic lymphocytic leukemia than females.

# Risk Factors
The most potent risk factor in the development of chronic lymphocytic leukemia is advanced age. Other risk factors include male gender, positive family history, and exposure to certain chemicals.

# Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for chronic lymphocytic leukemia.

# Natural History, Complications and Prognosis
Most patients with chronic lymphocytic leukemia are asymptomatic at the time of diagnosis. If left untreated, patients with chronic lymphocytic leukemia may progress to develop weight loss, fever, and lymphadenopathy. Common complications of chronic lymphocytic leukemia include immunodeficiency, warm autoimmune hemolytic anemia, and Richter's transformation. Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is 81.7%.

# Diagnosis

## Staging
According to the Rai Staging System, there are five stages of chronic lymphocytic leukemia based on the degree of lymphocytosis, hemoglobin concentration, platelets concentration, presence of splenomegaly, and presence of lymphadenopathy. While according to the Binet Staging System, there are three stages of chronic lymphocytic leukemia based on the degree of lymphocytosis, the presence of anemia or thrombocytopenia, and the involvement of three or more lymph node regions. The tumor stage is considered one of the important factors that determine the optimal management protocol of chronic lymphocytic leukemia patients.

## History and Symptoms
Symptoms of chronic lymphocytic leukemia include fever, weight loss, night sweats, and recurrent bleeding.

## Physical Examination
Physical examination of patients with chronic lymphocytic leukemia is usually remarkable for skin pallor, palpable cervical lymph nodes, and hepatomegaly.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of chronic lymphocytic leukemia include abnormal complete blood count, immunohistochemistry, and electrophoresis. Monoclonality of kappa and lambda producing B cells is a key diagnostic feature among patients with chronic lymphocytic leukemia.

## X Ray
There are no X ray findings associated with chronic lymphocytic leukemia.

## CT
CT scan is not required to confirm the diagnosis of chronic lymphocytic leukemia.

## MRI
MRI may be performed to detect spinal cord bone infiltration among chronic lymphocytic leukemia patients.

## Echocardiography or Ultrasound
There are no ultrasound findings associated with chronic lymphocytic leukemia.

## Other Imaging Findings
There are no other imaging studies needed to confirm the diagnosis of chronic lymphocytic leukemia.

## Other Diagnostic Studies
Bone marrow biopsy and lymph node biopsy  may be helpful in the diagnosis of chronic lymphocytic leukimea. Karyotyping and fluorescent in situ hybridization detect any chromosomal mutations involved in the development of chronic lymphocytic leukemia.

# Treatment

## Medical Therapy
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.

## Surgery
Surgical intervention is not recommended for the management of chronic lymphocytic leukemia patients.