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{{Chronic lymphocytic leukemia}}
{{Chronic lymphocytic leukemia}}
 
{{CMG}} {{AE}}{{HL}}
{{CMG}}; {{AE}} {{RT}}
 
==Overview==
==Overview==
Most [[Patient|patients]] with chronic lymphocytic leukemia are initially [[asymptomatic]]. If left untreated, [[Patient|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]]. [[Prognosis]] is generally good, and the 5-year [[survival rate]] of [[Patient|patients]] with chronic lymphocytic leukemia is 81.7%.


==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
===Natural History===
===Natural History===
The clinical course of [[chronic lymphocytic leukemia]] varies widely from patient to patient. Some patients die early because of complications, but most patients survive for 5 - 10 yrs.  The course of the disease is benign initially but followed by terminal, progressive and resistant phase which lasts for 1 - 2 yrs.
* Most [[Patient|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.


===Complications===
===Complications===
* [[Hypogammaglobulinemia]] leading to recurrent infection.
* Common complications of chronic lymphocytic leukemia include:<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="pmid107794222">{{cite journal |vauthors=Mauro FR, Foa R, Cerretti R, Giannarelli D, Coluzzi S, Mandelli F, Girelli G |title=Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features |journal=Blood |volume=95 |issue=9 |pages=2786–92 |date=May 2000 |pmid=10779422 |doi= |url=}}</ref><ref name="pmid8410123">{{cite journal |vauthors=Robertson LE, Pugh W, O'Brien S, Kantarjian H, Hirsch-Ginsberg C, Cork A, McLaughlin P, Cabanillas F, Keating MJ |title=Richter's syndrome: a report on 39 patients |journal=J. Clin. Oncol. |volume=11 |issue=10 |pages=1985–9 |date=October 1993 |pmid=8410123 |doi=10.1200/JCO.1993.11.10.1985 |url=}}</ref><ref name="pmid17986663">{{cite journal |vauthors=Visco C, Ruggeri M, Laura Evangelista M, Stasi R, Zanotti R, Giaretta I, Ambrosetti A, Madeo D, Pizzolo G, Rodeghiero F |title=Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia |journal=Blood |volume=111 |issue=3 |pages=1110–6 |date=February 2008 |pmid=17986663 |doi=10.1182/blood-2007-09-111492 |url=}}</ref>
* [[Autoimmune hemolytic anemia]] - IgG type
:* [[Richter's transformation]]  
* Transformation to high grade [[lymphoma]]
:* Recurrent [[infection]]s
* [[Richter's transformation]]
:* [[Anemia]]
* Gastrointestinal (GI) involvement - [[intussusception]], small intestinal bacterial contamination, [[colitis]]
:** [[Autoimmune]] [[thrombocytopenia]]
* Increased risk of other cancers - [[melanoma]], lung and gastrointestinal cancers
:** [[Red cells|Red cell]] [[aplasia]]  
:** [[Chemotherapy]]-induced [[anemia]]  
:* [[Immunity (medical)|Immune]] [[thrombocytopenia]]
:* [[Colitis]]
:* [[Intussusception]]
:* [[Small intestinal]] [[bacterial]] [[contamination]]
:* [[Tumor lysis syndrome]]
:* [[Constrictive pericarditis]]


===Prognosis===
===Prognosis===
The prognosis of chronic lymphocytic leukemia depends on:
* [[Prognosis]] is generally good, and the 5-year survival rate of [[Patient|patients]] with chronic lymphocytic leukemia is 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>
* Common [[prognostic]] factors for chronic lymphocytic leukemia [[Patient|patients]] include age, [[tumor]] stage, and the presence of certain [[genetic mutation]]s.<ref name="pmid267489322">{{cite journal |vauthors=Chen C, Puvvada S |title=Prognostic Factors for Chronic Lymphocytic Leukemia |journal=Curr Hematol Malig Rep |volume=11 |issue=1 |pages=37–42 |date=February 2016 |pmid=26748932 |doi=10.1007/s11899-015-0294-x |url=}}</ref>
* The table below lists [[prognostic]] factors for chronic lymphocytic leukemia [[Patient|patients]]:<ref name="pmid14576043">{{cite journal |vauthors=Shanafelt TD, Geyer SM, Kay NE |title=Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL |journal=Blood |volume=103 |issue=4 |pages=1202–10 |date=February 2004 |pmid=14576043 |doi=10.1182/blood-2003-07-2281 |url=}}</ref><ref name="pmid26748932">{{cite journal |vauthors=Chen C, Puvvada S |title=Prognostic Factors for Chronic Lymphocytic Leukemia |journal=Curr Hematol Malig Rep |volume=11 |issue=1 |pages=37–42 |date=February 2016 |pmid=26748932 |doi=10.1007/s11899-015-0294-x |url=}}</ref><ref name="pmid25461996" />
 
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px"
| valign="top" |
|+
! style="background: #4479BA; width: 250px; color: #FFFFFF;" |'''Prognostic Factor'''
 
! style="background: #4479BA; width: 600px; color: #FFFFFF;" |'''Description'''
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Age]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:* Older age at the time of [[diagnosis]] is associated with a worse [[prognosis]].
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Gender'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:* [[Male|Males]] are associated with a worse [[prognosis]] when compared to [[Female|females]].
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Performance status]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:* Patient's poor [[performance status]] is associated with a worse [[prognosis]].
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''Stage'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Binet stages B and C or Rai stages 2-4 are associated with a worse [[prognosis]].
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Lymphocyte]] [[doubling time]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*A rapid [[lymphocyte]] doubling time is associated with a worse [[prognosis]].
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Genetics|Genetic]] [[Mutation|mutations]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[Deletion (genetics)|Deletion]] of [[chromosome 17]] short arm and [[chromosome 11]] long arm are associated with a worse [[prognosis]].
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Prolymphocyte|Prolymphocytes]] [[Percentage|percent]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*An increased percentage of [[prolymphocyte]]s is associated with a worse prongnosis.
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Histological]] [[analysis]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*[[Diffuse]] [[histology]] on [[bone marrow aspiration]] is associated with a worse [[prognosis]].
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Lactate]] [[dehydrogenase]] ([[Lactate dehydrogenase|LDH]]) level'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Elevated level of [[LDH]] is associated with a worse [[prognosis]].
 
|-
 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''β2-microglobulin level '''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*Elevated level of β2-microglobulin is associated with a worse [[prognosis]].
 
|-


* The stage of [[chronic lymphocytic leukemia]], whether lymphocytes are spread throughout the bone marrow, whether the chronic lymphocytic leukemia progresses to lymphoma or prolymphocytic leukemia.
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Lymphocyte]] surface markers'''|| style="padding: 5px 5px; background: #F5F5F5;" |
* Treatment response: Whether the chronic lymphocytic leukemia patient gets better with treatment or has come back.
:*Over [[expression]] of [[CD38]] is associated with a worse [[prognosis]].
* The patient's general health.
|-
* [[Beta-2-microglobulin]] (higher levels imply a worse prognosis).
* Lymphocyte doubling time (doubling of the white blood cell count in excess of 1 year implies a favorable prognosis).
* Bone marrow histology - worse if histology is diffuse.


Survival varies from 5 years to more than 25 years.
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Immunoglobulin]] (Ig)[[VHL gene|VH gene]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*The absence of IgVH [[gene]] [[mutation]] is associated with a worse [[prognosis]].


====Gene mutation status====
|-
Recent publications suggest that two<ref name="pmid11733578">{{cite journal |author=Rosenwald A, Alizadeh AA, Widhopf G, ''et al'' |title=Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia |journal=J. Exp. Med. |volume=194 |issue=11 |pages=1639-47 |year=2001 |pmid=11733578 |doi=}}</ref> or three<ref name="pmid12406914">{{cite journal |author=Ghia P, Guida G, Stella S, ''et al'' |title=The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression |journal=Blood |volume=101 |issue=4 |pages=1262-9 |year=2003 |pmid=12406914 |doi=10.1182/blood-2002-06-1801}}</ref> prognostic groups of CLL exist based on the maturational state of the cell. This distinction is based on the maturity of the lymphocytes as discerned by the immunoglobulin variable-region [[heavy chain]] (IgV<sub>H</sub>) gene mutation status.<ref name="pmid16983131">{{cite journal |author=Shanafelt TD, Byrd JC, Call TG, Zent CS, Kay NE |title=Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia |journal=Ann. Intern. Med. |volume=145 |issue=6 |pages=435-47 |year=2006 |pmid=16983131 |doi=|url=http://www.annals.org/cgi/content/full/145/6/435}}</ref>  High risk patients have an immature cell pattern with few mutations in the DNA in the IgV<sub>H</sub> antibody gene region whereas low risk patients show considerable mutations of the DNA in the antibody gene region indicating mature lymphocytes.


Since assessment of the IgV<sub>H</sub> antibody DNA changes is difficult to perform, the presence of either [[cluster of differentiation]] [[CD38|38]] ([[CD38]]) or Z-chain–associated protein kinase-70 ([[ZAP-70]]) may be surrogate markers of high risk subtype of CLL.<ref name="pmid16983131"/> Their expression correlates with a more immature cellular state and a more rapid disease course.  Unmutated IgV<sub>H</sub> survive worse than mutated and are associated with aggressive CLL.  The ZAP70 (AKA Zeta-Associated Protein) presence on the CLL cell correlates with unmutated immunoglobulin genes and a poor prognosis. Conversely, its absence indicates the presence of mutated genes and a good clinical outcome.  Patients positive for ZAP70 have a CLL more aggressive in nature and more refractory to treatment.  They are more likely to evolve to more unfavorable cytogenetic abnormalitites.
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" align="center" | '''[[Membrane]]-bound [[Protein|proteins]]'''|| style="padding: 5px 5px; background: #F5F5F5;" |
:*The [[expression]] of [[Zeta-chain-associated protein 70 kD|zeta-chain-associated protein kinase]] 70 ([[ZAP-70|ZAP]]) is associated with a worse [[prognosis]].
|}


==References==
==References==

Latest revision as of 15:50, 28 February 2019

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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

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. Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is 81.7%.

Natural History, Complications and Prognosis

Natural History

Complications

  • Common complications of chronic lymphocytic leukemia include:[1][2][3][4]

Prognosis
Prognostic Factor Description
Age
Gender
Performance status
Stage
  • Binet stages B and C or Rai stages 2-4 are associated with a worse prognosis.
Lymphocyte doubling time
Genetic mutations
Prolymphocytes percent
  • An increased percentage of prolymphocytes is associated with a worse prongnosis.
Histological analysis
Lactate dehydrogenase (LDH) level
β2-microglobulin level
  • Elevated level of β2-microglobulin is associated with a worse prognosis.
Lymphocyte surface markers
Immunoglobulin (Ig)VH gene
Membrane-bound proteins

References

  1. ↑ 1.0 1.1 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. ↑ Mauro FR, Foa R, Cerretti R, Giannarelli D, Coluzzi S, Mandelli F, Girelli G (May 2000). "Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features". Blood. 95 (9): 2786–92. PMID 10779422.
  3. ↑ Robertson LE, Pugh W, O'Brien S, Kantarjian H, Hirsch-Ginsberg C, Cork A, McLaughlin P, Cabanillas F, Keating MJ (October 1993). "Richter's syndrome: a report on 39 patients". J. Clin. Oncol. 11 (10): 1985–9. doi:10.1200/JCO.1993.11.10.1985. PMID 8410123.
  4. ↑ Visco C, Ruggeri M, Laura Evangelista M, Stasi R, Zanotti R, Giaretta I, Ambrosetti A, Madeo D, Pizzolo G, Rodeghiero F (February 2008). "Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia". Blood. 111 (3): 1110–6. doi:10.1182/blood-2007-09-111492. PMID 17986663.
  5. ↑ SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia. National Cancer Institute (2015) http://seer.cancer.gov/statfacts/html/clyl.html Accessed on October, 12 2015
  6. ↑ Chen C, Puvvada S (February 2016). "Prognostic Factors for Chronic Lymphocytic Leukemia". Curr Hematol Malig Rep. 11 (1): 37–42. doi:10.1007/s11899-015-0294-x. PMID 26748932.
  7. ↑ Shanafelt TD, Geyer SM, Kay NE (February 2004). "Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL". Blood. 103 (4): 1202–10. doi:10.1182/blood-2003-07-2281. PMID 14576043.
  8. ↑ Chen C, Puvvada S (February 2016). "Prognostic Factors for Chronic Lymphocytic Leukemia". Curr Hematol Malig Rep. 11 (1): 37–42. doi:10.1007/s11899-015-0294-x. PMID 26748932.

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