Large granular lymphocytic leukemia: Difference between revisions
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{{Infobox medical condition (new) |
{{Infobox medical condition (new) |
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| name = Large granular lymphocytic leukemia |
| name = Large granular lymphocytic leukemia |
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| field = [[Hematology]], [[oncology]] |
| field = [[Hematology]], [[oncology]] |
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'''Large granular lymphocytic (LGL) leukemia''' is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular [[lymphocytes]] (LGLs) in the peripheral [[blood]].<ref name="who1">{{cite book |author=Elaine Sarkin Jaffe |author2=Nancy Lee Harris |author3=World Health Organization |author4=International Agency for Research on Cancer |author5=Harald Stein |author6=J.W. Vardiman |title=Pathology and genetics of tumours of haematopoietic and lymphoid tissues |publisher=IARC Press |location=Lyon |year=2001 |series=World Health Organization Classification of Tumors |volume=3 |isbn=978-92-832-2411-2 |url=https://books.google.com/books?id=XSKqcy7TUZUC}}</ref> |
'''Large granular lymphocytic (LGL) leukemia''' is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular [[lymphocytes]] (LGLs) in the peripheral [[blood]].<ref name="who1">{{cite book |author=Elaine Sarkin Jaffe |author2=Nancy Lee Harris |author3=World Health Organization |author4=International Agency for Research on Cancer |author5=Harald Stein |author6=J.W. Vardiman |title=Pathology and genetics of tumours of haematopoietic and lymphoid tissues |publisher=IARC Press |location=Lyon |year=2001 |series=World Health Organization Classification of Tumors |volume=3 |isbn=978-92-832-2411-2 |url=https://books.google.com/books?id=XSKqcy7TUZUC}}</ref> |
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It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, ''T-cell large granular lymphocyte leukemia'' is characterized by involvement of cytotoxic-[[T cell]]s).<ref name="pmid18791165">{{cite journal |vauthors=Epling-Burnette PK, Sokol L, Chen X, et al. |title=Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling |journal=Blood |volume=112 |issue=12 |pages=4694–8 |date=December 2008 |pmid=18791165 |doi=10.1182/blood-2008-02-136382 |pmc=2597136}}</ref> |
It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, ''T-cell large granular lymphocyte leukemia'' is characterized by involvement of cytotoxic-[[T cell]]s).<ref name="pmid18791165">{{cite journal |vauthors=Epling-Burnette PK, Sokol L, Chen X, et al. |title=Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling |journal=Blood |volume=112 |issue=12 |pages=4694–8 |date=December 2008 |pmid=18791165 |doi=10.1182/blood-2008-02-136382 |pmc=2597136}}</ref> |
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In a study based in the US, the average age of diagnosis was 66.5 years<ref>{{Cite journal| |
In a study based in the US, the average age of diagnosis was 66.5 years<ref>{{Cite journal|last1=Shah|first1=M V|last2=Hook|first2=C C|last3=Call|first3=T G|last4=Go|first4=R S|date=August 2016|title=A population-based study of large granular lymphocyte leukemia|journal=Blood Cancer Journal|language=En|volume=6|issue=8|pages=e455|doi=10.1038/bcj.2016.59|issn=2044-5385|pmc=5022177|pmid=27494824}}</ref> whereas in a French study the median age at diagnosis was 59 years (with an age range of 12–87 years old).<ref name=":0" /> In the French study, only 26% of patients were younger than 50 years which suggests that this disorder is associated with older age at diagnosis.<ref name=":0" /> Due to lack of presenting symptoms, the disorder is likely to be underdiagnosed in the general population.<ref>{{Cite journal|last=Kojić Katović|first=Sandra|date=2018|title=T-Cell Large Granular Lymphocytic Leukemia – Case Report|journal=Acta Clinica Croatica|language=en|volume=57|issue=2|pages=362–365|doi=10.20471/acc.2018.57.02.18|pmid=30431731|pmc=6531996|issn=0353-9466}}</ref> |
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==Signs and symptoms== |
==Signs and symptoms== |
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This disease is known for an indolent clinical course and incidental discovery.<ref name="who1"/> The most common physical finding is moderate [[splenomegaly]]. [[B symptoms]] are seen in a third of cases, and recurrent [[infections]] due to [[Anemia|anaemia]] and/or [[neutropenia]]<ref>{{Cite journal| |
This disease is known for an indolent clinical course and incidental discovery.<ref name="who1"/> The most common physical finding is moderate [[splenomegaly]]. [[B symptoms]] are seen in a third of cases, and recurrent [[infections]] due to [[Anemia|anaemia]] and/or [[neutropenia]]<ref name="auto">{{Cite journal|last1=Sanikommu|first1=Srinivasa R.|last2=Clemente|first2=Michael J.|last3=Chomczynski|first3=Peter|last4=Afable|first4=Manuel G.|last5=Jerez|first5=Andres|last6=Thota|first6=Swapna|last7=Patel|first7=Bhumika|last8=Hirsch|first8=Cassandra|last9=Nazha|first9=Aziz|date=2017-06-20|title=Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL)|journal=Leukemia & Lymphoma|language=en|volume=59|issue=2|pages=416–422|doi=10.1080/10428194.2017.1339880|pmid=28633612|pmc=8694069 |issn=1042-8194}}</ref> are seen in almost half of cases.<ref name="lam2">{{cite journal |title=Large Granular Lymphocyte Leukemia |journal=Cancer Control |volume=5 |issue=1 |pages=25–33 |date=January 1998 |pmid=10761014 |doi=10.1177/107327489800500103 |author=Lamy T, Loughran TP |doi-access= }}</ref><ref name="cha1">{{cite journal |vauthors=Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF |title=Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes |journal=Blood |volume=68 |issue=5 |pages=1142–53 |date=November 1986 |doi=10.1182/blood.V68.5.1142.1142 |pmid=3490288 |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=3490288|doi-access=free }}</ref><ref name="pan1">{{cite journal |vauthors=Pandolfi F, Loughran TP, Starkebaum G, et al. |title=Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study |journal=Cancer |volume=65 |issue=2 |pages=341–8 |date=January 1990 |pmid=2403836 |doi= 10.1002/1097-0142(19900115)65:2<341::AID-CNCR2820650227>3.0.CO;2-2|doi-access=free }}</ref><ref name="lam1">{{cite journal |author=Lamy T|name-list-style=vanc|title=Clinical features of large granular lymphocyte leukemia |journal=Semin. Hematol. |volume=40 |issue=3 |pages=185–95 |date=July 2003 |pmid=12876667 |doi= 10.1016/S0037-1963(03)00133-1|last2=Loughran |first2=TP }}</ref> |
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[[Rheumatoid arthritis]] is commonly observed in people with T-LGLL, leading to a clinical presentation similar to [[Felty's syndrome]].<ref name="lou3">{{cite journal |vauthors=Loughran TP, Starkebaum G, Kidd P, Neiman P |title=Clonal proliferation of large granular lymphocytes in rheumatoid arthritis |journal=Arthritis Rheum. |volume=31 |issue=1 |pages=31–6 |date=January 1988 |pmid=3345230 |doi= 10.1002/art.1780310105 |
[[Rheumatoid arthritis]] is commonly observed in people with T-LGLL, leading to a clinical presentation similar to [[Felty's syndrome]].<ref name="lou3">{{cite journal |vauthors=Loughran TP, Starkebaum G, Kidd P, Neiman P |title=Clonal proliferation of large granular lymphocytes in rheumatoid arthritis |journal=Arthritis Rheum. |volume=31 |issue=1 |pages=31–6 |date=January 1988 |pmid=3345230 |doi= 10.1002/art.1780310105}}</ref> Signs and symptoms of [[anemia]] are commonly found, due to the association between T-LGLL and [[erythroid]] [[hypoplasia]].<ref name="kwo1">{{cite journal |vauthors=Kwong YL, Wong KF |title=Association of pure red cell aplasia with T large granular lymphocyte leukaemia |journal=J. Clin. Pathol. |volume=51 |issue=9 |pages=672–5 |date=September 1998 |pmid=9930071 |pmc=500904 |doi= 10.1136/jcp.51.9.672|url=}}</ref> |
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===Sites of involvement=== |
===Sites of involvement=== |
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The requisite [[lymphocytosis]] of this disease is typically 2-20x10<sup>9</sup>/L.<ref name="kwo1"/> |
The requisite [[lymphocytosis]] of this disease is typically 2-20x10<sup>9</sup>/L.<ref name="kwo1"/> |
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Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.<ref name="lam1"/><ref name="osh1">{{cite journal |vauthors=Oshimi K, Yamada O, Kaneko T, et al. |title=Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders |journal=Leukemia |volume=7 |issue=6 |pages=782–8 |date=June 1993 |pmid=8388971 |
Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.<ref name="lam1"/><ref name="osh1">{{cite journal |vauthors=Oshimi K, Yamada O, Kaneko T, et al. |title=Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders |journal=Leukemia |volume=7 |issue=6 |pages=782–8 |date=June 1993 |pmid=8388971 }}</ref><ref name="lou1">{{cite journal |vauthors=Loughran TP, Starkebaum G, Aprile JA |title=Rearrangement and expression of T-cell receptor genes in large granular lymphocyte leukemia |journal=Blood |volume=71 |issue=3 |pages=822–4 |date=March 1988 |doi=10.1182/blood.V71.3.822.822 |pmid=3345349 |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=3345349|doi-access=free }}</ref><ref name="lou2">{{cite journal |vauthors=Loughran TP, Kadin ME, Starkebaum G, et al. |title=Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia |journal=Ann. Intern. Med. |volume=102 |issue=2 |pages=169–75 |date=February 1985 |pmid=3966754 |doi= 10.7326/0003-4819-102-2-169}}</ref> |
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===Peripheral blood=== |
===Peripheral blood=== |
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The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as [[perforin]] and [[granzyme B]].<ref name="sem1">{{cite journal |vauthors=Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP |title=The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis |journal=Blood |volume=89 |issue=1 |pages=256–60 |date=January 1997 | |
The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as [[perforin]] and [[granzyme B]].<ref name="sem1">{{cite journal |vauthors=Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP |title=The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis |journal=Blood |volume=89 |issue=1 |pages=256–60 |date=January 1997 |doi=10.1182/blood.V89.1.256 |pmid=8978299 |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=8978299}}</ref> [[Flow cytometry]] is also commonly used.<ref>{{Cite journal|last1=Lamy|first1=Thierry|last2=Loughran|first2=Thomas P.|date=2011-03-10|title=How I treat LGL leukemia|journal=Blood|language=en|volume=117|issue=10|pages=2764–2774|doi=10.1182/blood-2010-07-296962|issn=0006-4971|pmc=3062292|pmid=21190991}}</ref> |
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===Bone marrow=== |
===Bone marrow=== |
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The neoplastic cells of this disease display a mature [[T-cell]] [[immunophenotype]], with the majority of cases showing a [[CD4]]-/[[CD8]]+ T-cell subset [[immunophenotype]] versus other permutations of those markers.<ref name="cha1"/><ref name="pan1"/> Variable expression of [[CD11b]], [[CD56]], and [[CD57]]<ref name="lam1"/> are observed. Immunohistochemistry for [[perforin]], [[TIA-1]], and [[granzyme B]] are usually positive.<ref name="who1"/> |
The neoplastic cells of this disease display a mature [[T-cell]] [[immunophenotype]], with the majority of cases showing a [[CD4]]-/[[CD8]]+ T-cell subset [[immunophenotype]] versus other permutations of those markers.<ref name="cha1"/><ref name="pan1"/> Variable expression of [[CD11b]], [[CD56]], and [[CD57]]<ref name="lam1"/> are observed. Immunohistochemistry for [[perforin]], [[TIA-1]], and [[granzyme B]] are usually positive.<ref name="who1"/> |
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{| class="wikitable" |
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{| border="1" cellpadding="5" cellspacing="0" |
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! Type || Immunophenotype |
! Type || Immunophenotype |
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|- |
|- |
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|| Common type (80% of cases) |
|| Common type (80% of cases) |
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| style="text-align:center;"| [[CD3 (immunology)|CD3]]+, [[T-cell receptor|TCR]]αβ+, [[CD4]]-, [[CD8]]+ |
| style="text-align:center;"| [[CD3 (immunology)|CD3]]+, [[T-cell receptor|TCR]]αβ+, [[CD4]]-, [[CD8]]+ |
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|- style="text-align:center;" |
|- style="text-align:center;" |
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| rowspan="3"| Rare variants |
| rowspan="3"| Rare variants |
||
|| [[CD3 (immunology)|CD3]]+, [[T-cell receptor|TCR]]αβ+, [[CD4]]+, [[CD8]]- |
|| [[CD3 (immunology)|CD3]]+, [[T-cell receptor|TCR]]αβ+, [[CD4]]+, [[CD8]]- |
||
|- |
|- |
||
| style="text-align:center;"| [[CD3 (immunology)|CD3]]+, [[T-cell receptor|TCR]]αβ+, [[CD4]]+, [[CD8]]+ |
| style="text-align:center;"| [[CD3 (immunology)|CD3]]+, [[T-cell receptor|TCR]]αβ+, [[CD4]]+, [[CD8]]+ |
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===Genetic findings=== |
===Genetic findings=== |
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Clonal rearrangements of the [[T-cell receptor]] (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.<ref name="lou1"/><ref name="vie1">{{cite journal |vauthors=Vie H, Chevalier S, Garand R, et al. |title=Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder |journal=Blood |volume=74 |issue=1 |pages=285–90 |date=July 1989 | |
Clonal rearrangements of the [[T-cell receptor]] (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.<ref name="lou1"/><ref name="vie1">{{cite journal |vauthors=Vie H, Chevalier S, Garand R, et al. |title=Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder |journal=Blood |volume=74 |issue=1 |pages=285–90 |date=July 1989 |doi=10.1182/blood.V74.1.285.285 |pmid=2546620 |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=2546620|doi-access=free }}</ref> |
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Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy.<ref>{{Cite journal| |
Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy.<ref>{{Cite journal|last1=Shi|first1=Min|last2=He|first2=Rong|last3=Feldman|first3=Andrew L.|last4=Viswanatha|first4=David S.|last5=Jevremovic|first5=Dragan|last6=Chen|first6=Dong|last7=Morice|first7=William G.|date=March 2018|title=STAT3 mutation and its clinical and histopathologic correlation in T-cell large granular lymphocytic leukemia|journal=Human Pathology|volume=73|pages=74–81|doi=10.1016/j.humpath.2017.12.014|pmid=29288042|issn=0046-8177}}</ref> |
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==Treatment== |
==Treatment== |
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First line treatment is immunosuppressive therapy. A weekly dosage of [[Methotrexate]] (with or without daily [[Prednisone]]) may induce partial or complete response in some patients while others may require [[Cyclosporine]] or [[Cyclophosphamide]].<ref |
First line treatment is immunosuppressive therapy. A weekly dosage of [[Methotrexate]] (with or without daily [[Prednisone]]) may induce partial or complete response in some patients while others may require [[Cyclosporine]] or [[Cyclophosphamide]].<ref name="auto"/> |
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[[Alemtuzumab]] has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.<ref name="pmid14976065">{{cite journal |vauthors=Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH |title=Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia |journal=Blood |volume=103 |issue=5 |pages=1969–71 |date=March 2004 |pmid=14976065 |doi=10.1182/blood-2003-11-3951 }}</ref> |
[[Alemtuzumab]] has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.<ref name="pmid14976065">{{cite journal |vauthors=Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH |title=Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia |journal=Blood |volume=103 |issue=5 |pages=1969–71 |date=March 2004 |pmid=14976065 |doi=10.1182/blood-2003-11-3951 |doi-access=free }}</ref> |
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Experimental data suggests that treatment with [[Calcitriol|calcitrol]] (the active form of [[vitamin D]]) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines.<ref>{{Cite journal| |
Experimental data suggests that treatment with [[Calcitriol|calcitrol]] (the active form of [[vitamin D]]) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines.<ref>{{Cite journal|last1=Olson|first1=Kristine C.|last2=Kulling|first2=Paige M.|last3=Olson|first3=Thomas L.|last4=Tan|first4=Su-Fern|last5=Rainbow|first5=Rebecca J.|last6=Feith|first6=David J.|last7=Loughran|first7=Thomas P.|date=2016-10-07|title=Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL leukemia|journal=Cancer Biology & Therapy|language=en|volume=18|issue=5|pages=290–303|doi=10.1080/15384047.2016.1235669|issn=1538-4047|pmc=5499847|pmid=27715403}}</ref> |
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==Prognosis== |
==Prognosis== |
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==Epidemiology== |
==Epidemiology== |
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T-LGLL is a rare form of [[leukemia]], comprising 2-3% of all cases of chronic lymphoproliferative disorders. |
T-LGLL is a rare form of [[leukemia]], comprising 2-3% of all cases of chronic lymphoproliferative disorders.{{citation needed|date=November 2021}} |
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==History |
==History== |
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LGLL was discovered in 1985 by [[Thomas P. Loughran Jr.]] while working at [[Fred Hutchinson Cancer Research Center]].<ref>https://cancer.uvahealth.com/LGLLeBookNew.pdf</ref> Specimens from patients with LGLL are banked at the [[University of Virginia]] for research purposes, the only bank for such purposes.<ref>{{Cite web | url=https://cancer.uvahealth.com/cancers-we-treat/specialty-programs-clinics/lgl-leukemia | title=LGL Leukemia Program | UVA Health System}}</ref> |
LGLL was discovered in 1985 by [[Thomas P. Loughran Jr.]] while working at [[Fred Hutchinson Cancer Research Center]].<ref>{{Cite web |url=https://cancer.uvahealth.com/LGLLeBookNew.pdf |title=Archived copy |access-date=2016-12-12 |archive-date=2016-12-21 |archive-url=https://web.archive.org/web/20161221061035/https://cancer.uvahealth.com/LGLLeBookNew.pdf |url-status=dead }}</ref> Specimens from patients with LGLL are banked at the [[University of Virginia]] for research purposes, the only bank for such purposes.<ref>{{Cite web | url=https://cancer.uvahealth.com/cancers-we-treat/specialty-programs-clinics/lgl-leukemia | title=LGL Leukemia Program | UVA Health System}}</ref> |
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==References== |
==References== |
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== External links == |
== External links == |
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{{Medical resources |
{{Medical resources |
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| DiseasesDB = |
| DiseasesDB = |
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| ICD10 = |
| ICD10 = |
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| ICD9 = |
| ICD9 = |
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| ICDO = 9831/3 |
| ICDO = 9831/3 |
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| OMIM = |
| OMIM = |
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| MedlinePlus = |
| MedlinePlus = |
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| eMedicineSubj = |
| eMedicineSubj = |
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| eMedicineTopic = |
| eMedicineTopic = |
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| MeshID = D054066 |
| MeshID = D054066 |
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Latest revision as of 07:57, 14 October 2024
| Large granular lymphocytic leukemia | |
|---|---|
| Specialty | Hematology, oncology |
Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.[1]
It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells).[2]
In a study based in the US, the average age of diagnosis was 66.5 years[3] whereas in a French study the median age at diagnosis was 59 years (with an age range of 12–87 years old).[4] In the French study, only 26% of patients were younger than 50 years which suggests that this disorder is associated with older age at diagnosis.[4] Due to lack of presenting symptoms, the disorder is likely to be underdiagnosed in the general population.[5]
Signs and symptoms
[edit]This disease is known for an indolent clinical course and incidental discovery.[1] The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to anaemia and/or neutropenia[6] are seen in almost half of cases.[7][8][9][10]
Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome.[11] Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.[12]
Sites of involvement
[edit]The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.[1][7]
Cause
[edit]The postulated cells of origin of T-LGLL leukemia are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases.[1]
Diagnosis
[edit]Laboratory findings
[edit]The requisite lymphocytosis of this disease is typically 2-20x109/L.[12]
Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.[10][13][14][15]
Peripheral blood
[edit]The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as perforin and granzyme B.[16] Flow cytometry is also commonly used.[17]
Bone marrow
[edit]Bone marrow involvement in this disease is often present, but to a variable extent. Bone marrow biopsy is commonly used for diagnosis. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs.[1]
Immunophenotype
[edit]The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell subset immunophenotype versus other permutations of those markers.[8][9] Variable expression of CD11b, CD56, and CD57[10] are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive.[1]
| Type | Immunophenotype |
|---|---|
| Common type (80% of cases) | CD3+, TCRαβ+, CD4-, CD8+ |
| Rare variants | CD3+, TCRαβ+, CD4+, CD8- |
| CD3+, TCRαβ+, CD4+, CD8+ | |
| CD3+, TCRγδ+, CD4 and CD8 variable |
Genetic findings
[edit]Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.[14][18]
Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy.[19]
Treatment
[edit]First line treatment is immunosuppressive therapy. A weekly dosage of Methotrexate (with or without daily Prednisone) may induce partial or complete response in some patients while others may require Cyclosporine or Cyclophosphamide.[6]
Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.[20]
Experimental data suggests that treatment with calcitrol (the active form of vitamin D) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines.[21]
Prognosis
[edit]The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.[4]
Epidemiology
[edit]T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.[citation needed]
History
[edit]LGLL was discovered in 1985 by Thomas P. Loughran Jr. while working at Fred Hutchinson Cancer Research Center.[22] Specimens from patients with LGLL are banked at the University of Virginia for research purposes, the only bank for such purposes.[23]
References
[edit]- ^ a b c d e f Elaine Sarkin Jaffe; Nancy Lee Harris; World Health Organization; International Agency for Research on Cancer; Harald Stein; J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. Vol. 3. Lyon: IARC Press. ISBN 978-92-832-2411-2.
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- ^ "Archived copy" (PDF). Archived from the original (PDF) on 2016-12-21. Retrieved 2016-12-12.
{{cite web}}: CS1 maint: archived copy as title (link) - ^ "LGL Leukemia Program | UVA Health System".