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1566 Part XI: Malignant Lymphoid Diseases Chapter 94: Large Granular Lymphocytic Leukemia 1567

infection can lead to a mildly increased concentration of LGL cells; how- may be briefly effective as a single agent or accelerate the initial response
ever, in these patients the LGLs are not monoclonal. Reactive expan- to one of the first-line immunosuppressive agent. Glucocorticoids, how-
50
sions in LGLs may also be seen in the settings of other viral infections ever, do not have long-term efficacy in LGLL and neutropenia generally
such as CMV, postallogeneic stem cell transplantation, hyposplenism, recurs as soon as the medication is tapered. Because significant mor-
13
and pharmacologic tyrosine kinase inhibition. 13,51,52 Molecular studies bidity and mortality can result from chronic severe neutropenia and
to identify a clonal TCR gene rearrangement may be helpful in distin- transient responses to granulocyte- and granulocyte-monocyte colony-
guishing reactive from neoplastic LGL proliferations; however, reactive stimulating factors 64–66 have been reported, the judicious use of myeloid
clonal T-cell LGL expansions can occur. 53,54 X-chromosome inactivation growth factors may be advantageous in patients before surgical proce-
55
studies may be used to establish NK cell clonality in female patients. dures or during sepsis.
The immunophenotypic features described above may be useful to Methotrexate, cyclophosphamide, or cyclosporine, with or without
screen for an aberrant LGL population; however, reactive TCRγδ+ T prednisone, are usually effective in correcting the autoimmune cytope-
13
cells can show a similar pattern of surface expression including absence nias and the pure red cell aplasia associated with T-LGLL. In cases
of CD4 with or without dim partial CD8 and expression of NK-associ- of treatment failure with the three front-line therapies, the monoclonal
56
ated markers such as CD56 expression. The differential diagnosis also antibody alemtuzumab (Campath-1H), which targets CD52 expressed
includes blood, marrow, and/or spleen involvement by other T-cell neo- on the surface of T-cell LGLL, has been effective in case reports and
plasms. Often, the morphologic features in other T-cell neoplasms are small case series, including patients with refractory red cell aplasia. 67
more suggestive of malignancy compared to LGLL; however, this is not Splenectomy has been reported to produce responses in up to 50
59
always the case. The clinical history is also important to consider. For percent of patients with T-LGLL. However, splenectomy should be
example, both T-LGLL and hepatosplenic T-cell lymphoma (HSTCL) considered only for patients with resistant disease who have persistent
(Chap. 104) show a similar tissue distribution and with overlap in mor- evidence of severe cytopenia or symptomatic splenomegaly.
phologic features. However, HSTCL is more common in young men, Patients with chronic NK lymphocytosis usually do not require
whereas T-LGLL typically affects older individuals without a predilec- treatment.
tion for gender. Moreover, whereas T-LGLL cells express TIA-1, per-
forin, and granzyme B cytolytic granules, HSTCL characteristically
expresses TIA-1 but lacks perforin and granzyme B expression. 31,57,58 REFERENCES
Consequently, close attention to these subtle details is important in
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9
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59
weeks, and with acceptable and comparable safety profiles. The opti- 14. Lamy T, Liu JH, Landowski TH, et al: Dysregulation of CD95/CD95 ligand-apoptotic
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