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Chapter 78 Hairy Cell Leukemia 1269

TABLE Immunophenotype of Hairy Cell Leukemia and Other Indolent Lymphoid Neoplasms
78.2
Disease sIg CD5 CD10 CD11c CD20 CD22 CD23 CD25 CD103
HCL +/− −/+ − ++ + + −/+ + ++
CLL +/− ++ − −/+ +/− −/+ ++ −/+ −
B-PLL ++ + − −/+ +/− + +/− − −
HCLv +/− − − ++ + + − − −/+
MCL + ++ − − + + −/+ − −
SMZL + −/+ −/+ + + +/− −/+ − −
FL + − + − ++ + −/+ − −
B-PLL, B-prolymphocytic leukemia; CLL, chronic lymphocytic leukemia; FL, follicular lymphoma; HCLv, variant form of hairy cell leukemia; MCL, mantle cell lymphoma;
sIg, surface immunoglobulin; SMZL, splenic marginal zone lymphoma.

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monocytopenia. Splenomegaly and cytopenias are present in the include an absolute neutrophil count <1.0 × 10 /L, a platelet count
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majority of patients, and the pattern of bone marrow and splenic <100 × 10 /L, and/or a hemoglobin <12.0 g/dL.
involvement is similar to HCL and different from prolymphocytic
leukemia and SMZL. The immunophenotypic expression of various
lymphoid markers is also different in these disorders, with HCLv Historic Aspects of Therapy
lacking CD25 expression, further assisting diagnosis (Table 78.2).
Another aid in distinguishing HCL from HCLv is CD123 expres- Progress in the treatment of patients with HCL over the last 25 years
sion, which is positive in the former and negative in the latter. A has been significant, with survival curves now approaching those of
number of chromosomal abnormalities, including translocations, age-matched cohorts without the disease. Before the introduction of
have been reported in a few cases. Although HCLv has some similari- interferon (IFN)-α, splenectomy was used effectively to treat patients
ties to HCL, the two conditions differ in a number of features, most with HCL. Although splenectomy does not result in morphologic
notably being HCLv’s lack of responsiveness to classic HCL therapies. remissions in the bone marrow, the peripheral blood counts are normal-
As such, it is important to distinguish the two and consider them as ized in up to 70% of patients. Progression of disease can be expected
separate diseases. HCL and HCLv have different immunoglobulin in about 45% within 5 years. Furthermore, there is an associated
heavy (IGH) chain gene repertoires and somatic hypermutation morbidity and mortality with the procedure. As such, splenectomy is
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patterns. A recent report also suggested that high expression levels no longer performed in this disease except in rare, selected patients.
of AICD can distinguish HCL from HCLv, as well as from SMZL. The first report of effective treatment of HCL with IFN-α
However, the same group was unable to find distinct cytogenetic described several patients with progressive disease who received daily
events to distinguish HCL from its variant, using high-resolution doses of 3 million units. Three patients achieved CR with the other
genomic profiling. Most recently, BRAF V600F mutations have been four having partial responses (PR). The activity of IFN-α in HCL
shown to occur exclusively in HCL samples and not in those from was further confirmed by several large trials reporting CR rates of 4%
patients with HCLv and SMZL. to 30% and PR rates of 43% to 86%. Even in patients achieving a
SMZL (previously referred to as splenic lymphoma with villous CR, careful morphologic examination of the bone marrow revealed
lymphocytes [SLVL]) exhibits some of the clinical and morphologic residual hairy cells. With further follow up of patients treated with
features of HCL but typically has a more prominent peripheral blood IFN-α, it is clear that a significant proportion will relapse and require
involvement, lacks TRAP expression, and has a different immunophe- further therapy. However, the same authors reported that a number
notype, including absence of expression of CD25 and CD103. HCL of patients remaining alive after a 10-year follow up had not required
should be distinguished from other indolent lymphoid neoplasms such further therapy with interferon. The median failure-free survival
as chronic lymphocytic leukemia, prolymphocytic leukemia, and fol- reported by these and other investigators ranges from 6 to 25 months.
licular lymphomas, but this distinction is typically easily made using A number of predictors of outcome have been evaluated, with expres-
the characteristic morphologic and immunotypic findings characteristic sion of CD5 reported as a predictor of poor response.
of these disorders (see Table 78.2). Other disorders that should be The precise mechanism of action of IFN-α in HCL is unknown
included in the differential diagnosis include aplastic anemia, primary and may be related to the reduced production of a number of cyto-
myelofibrosis, and systemic mast cell disorders. kines such as granulocyte colony-stimulating factor, granulocyte-
macrophage colony-stimulating factor, IL-3, and IL-6. Others have
demonstrated that IFN-α can mediate apoptosis of hairy cells through
TREATMENT the effects of tumor necrosis factor-α.
Treatment with IFN-α is associated with significant toxicity
Indications for Therapy including flu-like symptoms, anorexia, fatigue, nausea and vomiting,
diarrhea, skin rash, peripheral neuropathy, and central nervous system
HCL has an indolent course, with some patients surviving many years dysfunction (such as depression and memory loss). This and the
without receiving therapy and others not requiring further therapy introduction of nucleoside analogs that are generally more effective
despite persistence of residual morphologic evidence of the disease in achieving responses has led to the use of interferon being limited
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after the initial treatment. Therefore a watch-and-wait strategy may to rare cases and special circumstances.
be appropriate in the initial management of patients with limited or
no manifestations of the disease. Disease progression that necessitates
therapy is commonly evident by the development of progressive Purine Nucleoside Analogs
cytopenias and their associated complications, such as infections,
bleeding, and progressive fatigue. No specific criteria for therapy have Although there are no specific guidelines for the treatment of HCL,
been established, but generally treatment is indicated when the monotherapy with cladribine or pentostatin is the current established
patient has significant cytopenias, symptomatic organomegaly or standard. Furthermore, despite the lack of a comparative study, a
adenopathy, infections, or constitutional symptoms such as fever, substantial number of data suggest that both drugs are equally effec-
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night sweats, or fatigue. Typical blood counts warranting therapy tive in terms of response rate and durability. The use of nucleoside