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Large granular lymphocytic leukemia

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Large granular lymphocytic leukemia
SpecialtyImmunology, oncology, angiology Edit this on Wikidata

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 categoires: T-cell LGL (T-LGL) leukemia and natural-killer (NK)-cell LGL (NK-LGL) leukemia. As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells). [2]

It is also known by the following terms: proliferation of large granular lymphocytes (LGLs), LGL leukemia, Tγ-lymphoproliferative disorder, and, in common with other T cell leukemias such as T-cell prolymphocytic leukemia, T-cell chronic lymphocytic leukemia.[1]

Epidemiology

T-LGL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.

Etiology

The postulated cells of origin of T-LGL 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]

Clinical features

Clinical presentation

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 the associated neutropenia are seen in almost half of cases.[3][4][5][6]

Rheumatoid arthritis is commonly observed in patients with T-LGL, leading to a clinical presentation similar to Felty's syndrome.[7] Signs and symptoms of anemia are commonly found, due to the association between T-LGL and erythroid hypoplasia.[8]

Laboratory findings

The requisite lymphocytosis of this disease is typically 2-20x109/L.[8]

Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.[6][9][10][11]

Sites of involvement

The leukemic cells of T-LGL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.[1][3]

Prognosis

The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.[12]

Morphology

Peripheral blood

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.[13]

Bone marrow

Bone marrow involvement in this disease is often present, but to a variable extent. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs.[1]

Molecular Findings

Immunophenotype

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.[4][5] Variable expression of CD11b, CD56, and CD57[6] 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

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.[10][14]

Treatment

Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.[15]

References

  1. ^ a b c d e f g 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 92-832-2411-6.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. ^ Epling-Burnette PK, Sokol L, Chen X, et al. (December 2008). "Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling". Blood. 112 (12): 4694–8. doi:10.1182/blood-2008-02-136382. PMC 2597136. PMID 18791165.
  3. ^ a b "Large Granular Lymphocyte Leukemia". Cancer Control. 5 (1): 25–33. January 1998. PMID 10761014.
  4. ^ a b Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF (November 1986). "Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes". Blood. 68 (5): 1142–53. PMID 3490288.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ a b Pandolfi F, Loughran TP, Starkebaum G, et al. (January 1990). "Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study". Cancer. 65 (2): 341–8. doi:10.1002/1097-0142(19900115)65:2<341::AID-CNCR2820650227>3.0.CO;2-2. PMID 2403836.
  6. ^ a b c Lamy T; Loughran, TP (July 2003). "Clinical features of large granular lymphocyte leukemia". Semin. Hematol. 40 (3): 185–95. doi:10.1016/S0037-1963(03)00133-1. PMID 12876667. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  7. ^ Loughran TP, Starkebaum G, Kidd P, Neiman P (January 1988). "Clonal proliferation of large granular lymphocytes in rheumatoid arthritis". Arthritis Rheum. 31 (1): 31–6. doi:10.1002/art.1780310105. PMID 3345230.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ a b Kwong YL, Wong KF; Wong, K. F. (September 1998). "Association of pure red cell aplasia with T large granular lymphocyte leukaemia". J. Clin. Pathol. 51 (9): 672–5. doi:10.1136/jcp.51.9.672. PMC 500904. PMID 9930071.
  9. ^ Oshimi K, Yamada O, Kaneko T, et al. (June 1993). "Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders". Leukemia. 7 (6): 782–8. PMID 8388971.
  10. ^ a b Loughran TP, Starkebaum G, Aprile JA (March 1988). "Rearrangement and expression of T-cell receptor genes in large granular lymphocyte leukemia". Blood. 71 (3): 822–4. PMID 3345349.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Loughran TP, Kadin ME, Starkebaum G, et al. (February 1985). "Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia". Ann. Intern. Med. 102 (2): 169–75. doi:10.7326/0003-4819-102-2-169. PMID 3966754.
  12. ^ Bareau, B; Rey, J; Hamidou, M; Donadieu, J; Morcet, J; Reman, O; Schleinitz, N; Tournilhac, O; et al. (2010). "Analysis of a French cohort of patients with large granular lymphocyte leukemia: A report on 229 cases". Haematologica. 95 (9): 1534–41. doi:10.3324/haematol.2009.018481. PMC 2930955. PMID 20378561.
  13. ^ Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP (January 1997). "The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis". Blood. 89 (1): 256–60. PMID 8978299.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Vie H, Chevalier S, Garand R, et al. (July 1989). "Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder". Blood. 74 (1): 285–90. PMID 2546620.
  15. ^ Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH (March 2004). "Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia". Blood. 103 (5): 1969–71. doi:10.1182/blood-2003-11-3951. PMID 14976065.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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