Chronic lymphocytic leukemia overview: Difference between revisions
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==Overview== | ==Overview== | ||
==Historical Perspective== | ==Historical Perspective== | ||
The first comprehensive clinical report of chronic lymphocytic leukemia was published by Dr. George Minot, an American physician, in 1924.<ref name="pmid8038488">{{cite journal| author=Rai KR| title=Progress in chronic lymphocytic leukaemia: a historical perspective. | journal=Baillieres Clin Haematol | year= 1993 | volume= 6 | issue= 4 | pages= 757-65 | pmid=8038488 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8038488 }} </ref> | |||
==Classification== | ==Classification== | ||
There is no classification system established for chronic lymphocytic leukemia. Common staging systems for chronic lymphocytic leukemia can be found [[Chronic lymphocytic leukemia clinical staging|'''here''']].<ref name="pmid1139039">{{cite journal| author=Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS| title=Clinical staging of chronic lymphocytic leukemia. | journal=Blood | year= 1975 | volume= 46 | issue= 2 | pages= 219-34 | pmid=1139039 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1139039 }} </ref> | |||
==Pathophysiology== | ==Pathophysiology== | ||
Chronic lymphocytic leukemia arises from pre-follicular center [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production. Development of chronic lymphocytic leukemia is the result of multiple [[genetic mutation]]s that promote both [[malignant]] leukemic proliferation and [[apoptotic]] resistance of mature B cells. Structural [[genetic mutation]]s 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.<ref name="wiki">Chronic Lymphocytic Leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref><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="patho">Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015</ref> | |||
==Causes== | ==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 [[Chronic lymphocytic leukemia pathophysiology|'''here''']].<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> | |||
==Differentiating Chronic Lymphocytic Leukemia from other Diseases== | ==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 node]]s, such as [[hairy cell leukaemia]], prolymphocytic leukaemia, [[follicular lymphoma]], and [[mantle cell lymphoma]].<ref name="H">Hoffbrand V, Moss P. Essential Haematology. John Wiley & Sons; 2011</ref> | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
In 2011, the age-adjusted [[incidence]] of chronic lymphocytic leukemia was 4.82 per 100,000 individuals in the United States.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref> Chronic lymphocytic leukemia is a disease of the elderly and is rarely encountered in individuals under the age of 40. Most 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== | ==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.<ref name="gov">What are the risk factors for chronic lymphocytic leukemia? American Cancer Society (2015) http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-risk-factors Accessed on October, 12 2015</ref><ref name="M"> Chronic Lymphocytic Leukemia. Mayoclinic (2015) http://www.mayoclinic.org/diseases-conditions/chronic-lymphocytic-leukemia/basics/risk-factors/con-20031195 Accessed on October, 12 2015</ref> | |||
==Screening== | ==Screening== | ||
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for chronic lymphocytic leukemia.<ref name="US">Recommendations. US preventive services task force (2015) http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=chronic+lymphocytic+leukemia+ Accessed on October, 12 2015</ref> | |||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
Most patients with [[chronic lymphocytic leukemia]] are initially asymptomatic. If left untreated, patients with [[chronic lymphocytic leukemia]] may progress to develop [[weight loss]], [[fever]], and [[lymph node]]s swelling. Common complications of chronic lymphocytic leukemia include [[immunodeficiency]], [[warm autoimmune hemolytic anemia]], and [[Richter's transformation]].<ref name="wiki">Chronic Lymphocytic Leukimea. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October ,12 2015</ref> Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is approximately 81.7%.<ref name="seer"> SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia. National Cancer Institute (2015) http://seer.cancer.gov/statfacts/html/clyl.html Accessed on October, 12 2015</ref> | |||
==Diagnosis== | ==Diagnosis== | ||
===Staging=== | ===Staging=== | ||
According to the Rai Staging System, there are five stages of chronic lymphocytic leukemia based on the degree of [[lymphocytosis]], [[hemoglobin]] level, [[platelet]]s level, presence of [[splenomegaly]], and presence of [[lymphadenopathy]].<ref name="pmid1139039">{{cite journal| author=Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS| title=Clinical staging of chronic lymphocytic leukemia. | journal=Blood | year= 1975 | volume= 46 | issue= 2 | pages= 219-34 | pmid=1139039 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1139039 }} </ref> 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.<ref name="pmid7237385">{{cite journal| author=Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J et al.| title=A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. | journal=Cancer | year= 1981 | volume= 48 | issue= 1 | pages= 198-206 | pmid=7237385 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7237385 }} </ref> The stage of the tumor is considered one of the important factors that determine the optimal management protocol of chronic lymphocytic leukemia patients.<ref name="pmid25461996">Nabhan C, Rosen ST (2014) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=25461996 Chronic lymphocytic leukemia: a clinical review.] ''JAMA'' 312 (21):2265-76. [http://dx.doi.org/10.1001/jama.2014.14553 DOI:10.1001/jama.2014.14553] PMID: [http://pubmed.gov/25461996 25461996]</ref> | |||
===History and Symptoms=== | ===History and Symptoms=== | ||
Symptoms of chronic lymphocytic leukemia include [[fever]], [[weight loss]], [[night sweats]], and recurrent [[ bleeding]].<ref name="wiki">Chronic Lymphocytic Leukimea. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October ,12 2015</ref> | |||
===Physical Examination=== | ===Physical Examination=== | ||
Physical examination of patients with chronic lymphocytic leukemia is usually remarkable for skin [[pallor]], palpable [[cervical]] [[lymph node]]s, and [[hepatomegaly]].<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="wiki">Chronic Lymphocytic Leukimea. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October ,12 2015</ref> | |||
===Laboratory Findings=== | ===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 cell]]s is a key diagnostic feature among patients with chronic lymphocytic leukemia.<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="wiki">Chronic Lymphocytic Leukimea. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October ,12 2015</ref> | |||
===X Ray=== | ===X Ray=== | ||
There are no X ray findings associated with chronic lymphocytic leukemia.<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="radio">Chronic lymphocytic leukemia. Dr Yuranga Weerakkody Radiopaedia (2015) http://radiopaedia.org/articles/chronic-lymphocytic-leukaemia Accessed on October, 14 2015</ref> | |||
===CT=== | ===CT=== | ||
There are no CT scan findings associated with chronic lymphocytic leukemia.<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="radio">Chronic lymphocytic leukemia. Dr Yuranga Weerakkody Radiopaedia (2015) http://radiopaedia.org/articles/chronic-lymphocytic-leukaemia Accessed on October, 14 2015</ref> | |||
===MRI=== | ===MRI=== | ||
MRI may be performed to detect spinal cord bone infiltration among chronic lymphocytic leukemia patients.<ref name="radio">Chronic lymphocytic leukemia. Dr Yuranga Weerakkody Radiopaedia (2015) http://radiopaedia.org/articles/chronic-lymphocytic-leukaemia Accessed on October, 14 2015</ref> | |||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
Revision as of 17:45, 17 October 2015
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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
Historical Perspective
The first comprehensive clinical report of chronic lymphocytic leukemia was published by Dr. George Minot, an American physician, in 1924.[1]
Classification
There is no classification system established for chronic lymphocytic leukemia. Common staging systems for chronic lymphocytic leukemia can be found here.[2]
Pathophysiology
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.[3][4][5][6]
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.[5]
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.[7]
Epidemiology and Demographics
In 2011, the age-adjusted incidence of chronic lymphocytic leukemia was 4.82 per 100,000 individuals in the United States.[8] Chronic lymphocytic leukemia is a disease of the elderly and is rarely encountered in individuals under the age of 40. Most 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.[9][10]
Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for chronic lymphocytic leukemia.[11]
Natural History, Complications and Prognosis
Most patients with chronic lymphocytic leukemia are initially asymptomatic. If left untreated, patients with chronic lymphocytic leukemia may progress to develop weight loss, fever, and lymph nodes swelling. Common complications of chronic lymphocytic leukemia include immunodeficiency, warm autoimmune hemolytic anemia, and Richter's transformation.[3] Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is approximately 81.7%.[12]
Diagnosis
Staging
According to the Rai Staging System, there are five stages of chronic lymphocytic leukemia based on the degree of lymphocytosis, hemoglobin level, platelets level, presence of splenomegaly, and presence of lymphadenopathy.[2] 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.[13] The stage of the tumor is considered one of the important factors that determine the optimal management protocol of chronic lymphocytic leukemia patients.[4]
History and Symptoms
Symptoms of chronic lymphocytic leukemia include fever, weight loss, night sweats, and recurrent bleeding.[3]
Physical Examination
Physical examination of patients with chronic lymphocytic leukemia is usually remarkable for skin pallor, palpable cervical lymph nodes, and hepatomegaly.[4][3]
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.[4][3]
X Ray
There are no X ray findings associated with chronic lymphocytic leukemia.[4][14]
CT
There are no CT scan findings associated with chronic lymphocytic leukemia.[4][14]
MRI
MRI may be performed to detect spinal cord bone infiltration among chronic lymphocytic leukemia patients.[14]
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
References
- ↑ Rai KR (1993). "Progress in chronic lymphocytic leukaemia: a historical perspective". Baillieres Clin Haematol. 6 (4): 757–65. PMID 8038488.
- ↑ 2.0 2.1 Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS (1975). "Clinical staging of chronic lymphocytic leukemia". Blood. 46 (2): 219–34. PMID 1139039.
- ↑ 3.0 3.1 3.2 3.3 3.4 Chronic Lymphocytic Leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
- ↑ 5.0 5.1 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.
- ↑ Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015
- ↑ Hoffbrand V, Moss P. Essential Haematology. John Wiley & Sons; 2011
- ↑ Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.
- ↑ What are the risk factors for chronic lymphocytic leukemia? American Cancer Society (2015) http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-risk-factors Accessed on October, 12 2015
- ↑ Chronic Lymphocytic Leukemia. Mayoclinic (2015) http://www.mayoclinic.org/diseases-conditions/chronic-lymphocytic-leukemia/basics/risk-factors/con-20031195 Accessed on October, 12 2015
- ↑ Recommendations. US preventive services task force (2015) http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=chronic+lymphocytic+leukemia+ Accessed on October, 12 2015
- ↑ SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia. National Cancer Institute (2015) http://seer.cancer.gov/statfacts/html/clyl.html Accessed on October, 12 2015
- ↑ Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J; et al. (1981). "A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis". Cancer. 48 (1): 198–206. PMID 7237385.
- ↑ 14.0 14.1 14.2 Chronic lymphocytic leukemia. Dr Yuranga Weerakkody Radiopaedia (2015) http://radiopaedia.org/articles/chronic-lymphocytic-leukaemia Accessed on October, 14 2015