Page 1582 - Williams Hematology ( PDFDrive )

1556 Part XI: Malignant Lymphoid Diseases Chapter 93: Hairy Cell Leukemia 1557

those seen in splenic marginal lymphoma with villous lymphocytes.
Patients usually have very large spleens, leukopenia, and thrombocy-
topenia. The immunophenotypic profile shows strong expression of
CD20 and negative staining for CD25, CD11c, CD123, and annexin.
This indolent lymphoma has been reported to respond to splenectomy.
There are patients with classic appearing HCL who have molecular
features suggesting that there may be more than one molecular “variant”
of this disease. For example, patients with a classic immunophenotype
H&E Reticulin who are BRAF V600E mutation-negative and use the immunoglobulin
VH4–34 have a worse prognosis than those with HCL-c, despite hav-
ing identical immunophenotypic markers. 19,35 Patients with unmutated
immunoglobulin gene rearrangement and those harboring a p53 muta-
tion also have a worse prognosis, indicating that these molecular fea-
tures potentially define yet another form of this disease. Further study
31
of the molecular prognostic features will hopefully identify informa-
tion that will enable improvement in selection of appropriate therapy.
19
Establishing an accurate diagnosis of HCL or one of the clinical entities
CD20 V600E BRAF
that mimic this disease by including a complete set of immunopheno-
typic and molecular markers is essential in selecting the best therapeutic
option for each patient (Table 93–1).

THERAPY
CRITERIA FOR INITIATION OF TREATMENT
Patients with HCL should be treated for symptoms related to the disease
Annexin A1 DBA44
or for deterioration in blood counts. Patients may have symptoms asso-
Figure 93–2. Marrow core biopsy is important in diagnosis of hairy cell ciated with a markedly enlarged spleen. Excessive fatigue related either
leukemia (HCL) because marrow aspirates are frequently dry taps in HCL. to the underlying disease or to the degree of anemia also warrant treat-
This figure shows a marrow trephine biopsy involved by HCL. Hematoxy- ment. If the absolute neutrophil count is documented to be less than
lin-and-eosin (H&E) stained sections show a characteristic interstitial pat- 1,000/μL or if the platelet count is confirmed to be less than 100,000/μL,
tern of marrow infiltration by HCL. Leukemic cells are medium size with then consideration for treatment should be given rather than waiting
ample clear cytoplasm and centrally placed nuclei without nucleoli with until the patient’s blood counts have deteriorated to very low levels.
“fried egg” morphology. Leukemic cells do not form discrete aggregates
but are admixed with hematopoietic elements that often render their Many patients will have achieved these low hematologic parameters
distinction from background erythroid precursors difficult. Reticulin stain by the time of diagnosis, therefore meriting prompt therapy. Approx-
shows reticulin fibrosis that is characteristically present in marrow involved imately 10 percent of patients with HCL-c may not meet these criteria,
by HCL and renders marrow difficult to aspirate resulting in frequent dry and can be followed for an extended period of time without therapy,
tap aspirates. CD20 immunohistochemical stain highlights the extent of albeit with close followup. 60,62,63
leukemic infiltrate. V600E BRAF immunohistochemical stain highlights leu- If patients have had recurrent infections requiring antibiotics, it
kemic cells that typically are positive for V600E BRAF mutation. Annexin A1 may be prudent to delay treatment for the HCL until after the infec-
immunohistochemical stain is positive in leukemic cells and is negative in tion has been controlled. After the infection is controlled, subsequent
background residual erythroid cells. DBA44 immunohistochemical stain, treatment with a purine analogue can be administered to secure a con-
while not absolutely specific, is always positive in HCL.
solidated remission of the leukemia. These challenges highlight the
importance of starting effective anti-leukemic therapy before the abso-
lute neutrophil count deteriorates to a dangerous level.
indolent, but eventually progresses with spleen and liver involvement.
Some patients respond to splenectomy with temporary stabilization
of the disease. Patients do not achieve durable responses with purine STANDARD APPROACH
analogues as monotherapy, but may respond to immunotoxin conju- Patients may either be treated with cladribine or pentostatin
gates (e.g., HA-22) or combined therapies with a purine analogue and a (Table 93–2). 62,67,68 Cladribine has been approved for initial therapy, and
monoclonal antibody. 65,66 pentostatin has been approved for second-line therapy. Cladribine has
Another entity that must be distinguished from HCL is splenic been administered by several routes on differing schedules. This agent
marginal zone lymphoma/splenic marginal zone lymphoma with villous is usually administered over 5 to 7 days, and the patient’s blood counts
lymphocytes. This entity is a chronic B-cell neoplasm that involves the need to be carefully monitored after this initial course. Initial studies
64
spleen, splenic hilar nodes, marrow and the blood. Patients may present administered cladribine as a continuous intravenous infusion for 7 days
with splenomegaly, anemia, and thrombocytopenia. The malignant cells as a single course. Subsequently, other investigators administered this
10
in the blood are characterized by cytoplasmic villi/projections that are agent as a daily intravenous infusion over 2 hours each day for 5 days.
68
typically polar in distribution. The immunophenotypic profile is dis- Approximately 4 to 6 months after blood count recovery following clad-
tinctly different than HCL-c. While the cells are positive for CD20, they ribine, a marrow biopsy should be obtained to determine the quality
are negative for CD25, annexin 1, and usually negative for CD103. of the response. The overall complete remission rate with this agent is
Splenic diffuse red pulp small B-cell lymphoma is an uncommon reported to vary from 75 percent to 91 percent. 67,69,70
64
lymphoma that infiltrates the splenic red pulp in a diffuse pattern. It Alternatively, if pentostatin is to be used for induction therapy,
can also involve the marrow and the blood. The malignant cells resemble it is administered once every 2 weeks as a short intravenous injection

Kaushansky_chapter 93_p1553-1562.indd 1557 9/18/15 3:47 PM