Chronic lymphocytic leukemia clinical staging: Difference between revisions
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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. | 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 | 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. | ||
==References== | ==References== |
Revision as of 13:20, 7 August 2012
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Classification
Clinical staging
Staging is done with the Rai staging system and the Binet classification (see details[1]).
Rai staging system
Stage 0 | Absolute lymphocytosis (>15,000/mm3) without adenopathy, hepatosplenomegaly, anemia, or thrombocytopenia. |
Stage 1 | Absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia. |
Stage 2 | Absolute lymphocytosis with either hepatomegaly or splenomegaly with or without lymphadenopathy. |
Stage 3 | Absolute lymphocytosis and anemia (hemoglobin <11 g/dL) with or without lymphadenopathy, hepatomegaly, or splenomegaly. |
Stage 4 | Absolute lymphocytosis and thrombocytopenia (<100,000/mm3) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia. |
Binet Classification
Clinical stage A | No anemia or thrombocytopenia and fewer than three areas of lymphoid involvement (Rai stages 0, I, and II). |
Clinical stage B | No anemia or thrombocytopenia with three or more areas of lymphoid involvement (Rai stages I and II). |
Clinical stage C | Anemia and/or thrombocytopenia regardless of the number of areas of lymphoid enlargement (Rai stages III and IV). |
Gene mutation status
Recent publications suggest that two[2] or three[3] 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 (IgVH) gene mutation status.[4] High risk patients have an immature cell pattern with few mutations in the DNA in the IgVH 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 IgVH antibody DNA changes is difficult to perform, the presence of either cluster of differentiation 38 (CD38) or Z-chain–associated protein kinase-70 (ZAP-70) may be surrogate markers of high risk subtype of CLL.[4] Their expression correlates with a more immature cellular state and a more rapid disease course. Unmutated IgVH 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.
References
- ↑ National Cancer Institute. "Chronic Lymphocytic Leukemia (PDQ®) Treatment: Stage Information". Retrieved 2007-09-04.
- ↑ Rosenwald A, Alizadeh AA, Widhopf G; et al. (2001). "Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia". J. Exp. Med. 194 (11): 1639–47. PMID 11733578.
- ↑ Ghia P, Guida G, Stella S; et al. (2003). "The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression". Blood. 101 (4): 1262–9. doi:10.1182/blood-2002-06-1801. PMID 12406914.
- ↑ 4.0 4.1 Shanafelt TD, Byrd JC, Call TG, Zent CS, Kay NE (2006). "Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia". Ann. Intern. Med. 145 (6): 435–47. PMID 16983131.