Page 1224 - Williams Hematology ( PDFDrive )

1199

CHAPTER 79 mononucleosis (Chap. 82), large granular lymphocytes associated with
large granular lymphocytic leukemia (Chap. 94), smudge cells associ-
LYMPHOCYTOSIS AND ated with chronic lymphocytic leukemia (CLL; Chap. 92), or blasts of
acute lymphocytic leukemia (Chap. 91). Chapter 73 provides a descrip-
LYMPHOCYTOPENIA tion of normal lymphocyte morphology.
Characterization of cell-surface markers is valuable in distinguish-
ing primary lymphocytosis (leukemic) from secondary lymphocytosis
(reactive). Improvements in flow cytometric techniques and reagents
Sumithira Vasu and Michael A. Caligiuri have allowed clinical laboratories to perform flow cytometric immuno-
phenotyping to distinguish benign from neoplastic lymphoproliferative
1
disease. Analysis for immunoglobulin or T-cell receptor gene rear-
rangement also may provide evidence for monoclonal B-cell or T-cell
SUMMARY proliferation, respectively. 1,2

Lymphocytosis is defined as an absolute lymphocyte count exceeding 4 ×
10 /L, whereas lymphocytopenia is defined as a total lymphocyte count less PRIMARY LYMPHOCYTOSIS
9
than 1.0 × 10 /L. Lymphocytosis can be categorized as either polyclonal or Primary lymphocytosis defines conditions associated with an increase
9
monoclonal. Monoclonal lymphocytosis reflects an underlying clonal lymphoid in the absolute number of lymphocytes secondary to an intrinsic defect
disease in which the numbers of lymphocytes are increased because of the in the expanded lymphocyte population (Table 79–1). These conditions
acquisition of somatic mutations resulting in clonal expansion of a lympho- also are referred to as lymphoproliferative disorders and most commonly
cyte progenitor. This expansion can be stable, such as monoclonal B-cell lym- are secondary to the neoplastic accumulation of monoclonal B cells,
phocytosis or a progressive malignancy such as acute lymphocytic leukemia, T cells, natural killer (NK) cells, or less fully differentiated cells of the
whereas polyclonal lymphocytosis is most commonly the result of stimulation lymphoid lineage. Table 79–1 lists the chapters describing each of these
or a reaction to factors extrinsic to lymphocytes, generally infections and/or conditions.
Although patients with lymphocytosis secondary to lymphopro-
inflammation. Lymphocytopenia, on the other hand, typically reflects deple- liferative disease generally maintain abnormal lymphocyte counts that
tion of T cells, the most abundant lymphocyte subtype in the blood. The most rise over time, this finding is not invariable. Patients with large granular
common cause of such T-cell depletion is a viral infection, such as infection lymphocytic leukemia (Chap. 94) may have only transient lymphocyto-
with the human immunodeficiency virus, although other causes exist. This sis that is induced by stress or exercise.
chapter outlines the conditions associated with abnormalities in the num-
bers of circulating lymphocytes in the blood. It also serves as a useful road Monoclonal B-Cell Lymphocytosis
map to other chapters in the book that describe in detail those conditions The advent of multiparameter flow cytometric and molecular diagnostic
that commonly are associated with abnormalities in the absolute numbers of techniques has identified a syndrome in patients who have expanded
circulating lymphocytes. populations of monoclonal B cells without other associated clinical
signs or symptoms. This condition, monoclonal B-cell lymphocytosis
3
(MBL) has generated a series of clinical and biologic studies investigat-
ing the prognosis and implications of this condition. An absolute B-cell
LYMPHOCYTOSIS count of less than 5.0 × 10 /L rather than the absolute lymphocyte count
9
is used to distinguish MBL from CLL (Chap. 92). This threshold is
4
DEFINITION essentially arbitrary and is not based on objective clinical outcome data.
Lymphocytosis is defined as an absolute lymphocyte count exceeding MBL could be diagnosed in two situations: in subjects with a normal
4 × 10 /L, although somewhat higher threshold values (e.g., >5.0 × 10 /L) lymphocyte count via a screening assay (screening MBL) or during a
9
9
5–8
are sometimes used. The normal absolute lymphocyte count is signifi- clinical evaluation of lymphocytosis (clinical MBL). Screening MBL,
cantly higher in childhood. Chapter 2 describes the methods for deter- also commonly referred to as low-count MBL (<500 monoclonal B cells
mining the absolute lymphocyte count and the normal range for such per μL) is diagnosed when high-sensitivity flow cytometric techniques
counts in older children and adults (see Chap. 2, Tables 2–1 and 2–2). are used in unaffected sibling families with a genetic predisposition to
9
Tables 7–3 and 7–4 in Chapter 7, provide the lymphocyte counts and CLL. Prevalence of screening MBL increases with age from 2.1 percent
lymphocyte subset counts in newborns and infants. in individuals between 40 and 60 years of age up to 5 percent in indi-
10
The blood film of patients with lymphocytosis should be evaluated viduals older than age 60 years. Single-cell analysis in familial CLL
for a predominance of reactive lymphocytes associated with infectious kindreds showed oligoclonality, suggesting a model of stepwise pro-
gression to CLL. MBL also has been detected in blood donors, with a
11
prevalence of 6.0 to 8.3 percent in donors age 45 years or older. This
12
study detected presence of a MBL clone in 149 of 2098 donors, showing
that MBL prevalence is much higher in blood donors than previously
13
Acronyms and Abbreviations: BNP, brain natriuretic peptide; CLL, chronic lym- reported. This finding has generated interest given a meta-analysis
phocytic leukemia; CML, chronic myelogenous leukemia; CMV, cytomegalovirus; showing higher risk of non-Hodgkin lymphoma and CLL in patients
14
EBV, Epstein-Barr virus; GVHD, graft-versus-host disease; IFN-γ, interferon-gamma; who received blood transfusions. Individuals with known clinical
Ig, immunoglobulin; IL, interleukin; LCK, lymphocyte-specific kinases; LGLL, large MBL should not be considered suitable for blood donation. Whether
granular lymphocytic leukemia; MBL, monoclonal B-cell lymphocytosis; miRNA, this applies to screening MBL is a matter of investigation. The 10 per-
microRNA; NK, natural killer; PPBL, persistent polyclonal B-cell lymphocytosis; TCR, cent prevalence of screening MBL among relatives of patients with CLL
T-cell receptor; UNC, uncoordinated; WHO, World Health Organization. has led to questions concerning their suitability as stem cell donors for
patients with CLL requiring allogeneic stem cell transplantation. 15

Kaushansky_chapter 79_p1199-1210.indd 1199 9/17/15 4:06 PM