93 Large Granular Lymphocytic Leukemia Flashcards
The presence of interstitial and/or intrasinusoidal clusters of at least ____ CD8+ and/or TIA-1+ LGLs or at least ____ granzyme B+ LGLs has been correlated with marrow involvement by LGLL.
Eight, six
The marrow biopsy in T-LGLL may be hypo-, normo-, or hypercellular, with often preserved trilineage hematopoiesis.
There may be occasional nodules of reactive CD4+ and B lymphocytes as well as scattered LGL, which are better seen in the aspirate.
Large Granular Lymphocytic (LGL) Leukemia is primarily characterized by the proliferation of which type of cells
T lymphocytes or NK cells
A common clinical feature of LGL leukemia includes:
Neutropenia (80%)
Anemia (45%)
The T-LGL leukemia is often associated with which underlying condition
Autoimmune disorders, particularly rheumatoid arthritis
Results from an indolent clonal expansion of large granular lymphocytes (LGLs) with a T-cell (CD3+) phenotype and a clonal T-cell receptor gene rearrangement(s), usually α and β chains.
T-cell large granular lymphocytic leukemia (T-LGLL)
A clonal expansion of LGL with a NK cell (CD3–) phenotype.
It lacks convenient markers to determine clonality, such as antigen receptor rearrangements.
Chronic lymphoproliferative disorders of natural killer cells (CLPD-NK)
In the Eastern Cooperative Oncology Group (ECOG) 5998 study, the cut off for the diagnosis of LGL leukemia is greater than ____, with a TCRαβ+/CD3+/CD8+/CD57+ immunophenotype, lasting more than ______.
0.50 × 10^9/L
6 months
CD5 is dimly expressed
In the Eastern Cooperative Oncology Group (ECOG) 5998 study, the cut off for diagnosis of CLDP-NK (CD3–/CD8+/CD16+ and/or (CD16+/CD56+) is:
NK-LGL leukemia cells typically express CD2, CD16, and CD56 markers.
Greater than 0.75 × 10^9/L
Appear to be the key cytokines regulating LGLL proliferation and survival.
Platelet-derived growth factor (PDGF) and interleukin (IL)-15
Overexpression of Fas (CD95) and the Fas ligand (CD178), which also is found at high levels in patients’ sera, may also contribute to the LGL proliferation.
A hallmark of LGLLs
Chronic activation of the JAK/STAT3 pathway
TRUE OR FALSE
About half the patients with T-LGLL are asymptomatic at diagnosis, and diagnosis is based on examination of blood.
TRUE
About half the patients with T-LGLL are asymptomatic at diagnosis, and diagnosis is based on examination of blood.
LGLL is the most commonly associated disease in patients with this condition
Pure red cell aplasia
Indications for therapy for LGLL
- (a) severe neutropenia (<0.5 × 109/L) or moderate neutropenia (0.5–1.5 × 109/L) with recurrent infections
- (b) symptomatic or transfusion-dependent anemia
- (c) moderately severe thrombocytopenia (<50 × 109/L)
- (d) associated autoimmune conditions requiring therapy
Given the immune-suppressive, rather than cytoreductive, manner in which these agents work in T-LGLL, patients should remain on an individual agent for a minimum of ________ months before assessing disease response.
Four
For patients with indications for treatment, the most common treatment approach is chronic immunosuppression with low-dose oral methotrexate (MTX), cyclophosphamide, or cyclosporine
In most patients with a clinical response, the T-LGLL clone typically persists however cyclophosphamide can temporarily eradicate the T-LGLL clone.
This monoclonal antibody targets CD52 expressed on the surface of T cells and may be used for patients with relapsed/refractory T-LGLL
Alemtuzumab
