92 Hairy Cell Leukemia

Question 1

The distinctive feature of Hairy Cell Leukemia

Answer 1

Cytoplasmic projections

Question 2

Three separate malignancies were identified as being of particular concern in terms of increased overall risk in patients with hairy cell leukemia

Answer 2

Hodgkin lymphoma
Non-Hodgkin lymphoma
Thyroid cancer

Question 3

HCL is a rare chronic B-cell lymphoid malignancy accounting for approximately ____ of adult leukemias

Answer 3

2%

Question 4

There is an unexplained_________ predominance with this disease with a ratio of 4 to 1.

Answer 4

Male

• The mean age at diagnosis is 55 years
• There is also an unexplained racial difference with more than 90% of patients in the United States being of European origin.

Question 5

TRUE OR FALSE

Younger patients respond better to therapy but may relapse and require retreatment to experience long-term survival benefits.

Answer 5

TRUE

Younger patients respond better to therapy but may relapse and require retreatment to experience long-term survival benefits.

Question 6

TRUE OR FALSE

In patients who have mutated immunoglobulin genes, the disease appears to be more aggressive, as is the case in chronic lymphocytic leukemia.

Answer 6

FALSE

In patients who have unmutated immunoglobulin genes, the disease appears to be more aggressive, as is the case in chronic lymphocytic leukemia.

The neoplastic cells in classic HCL-c have hypermutated immunoglobulin genes in approximately 90% of the cases.

Question 7

Prognosis: favorable or poor

Presence of VH4–34 gene

Answer 7

Poor

Question 8

Prognosis: favorable or poor

p53

Answer 8

Poor

Question 9

This mutation is detected in almost 100% of patients with HCL-c

Answer 9

BRAF V600E

Highly responsive form

Variant of HCL (HCL-v) express BRAF wild type

Question 10

The most common presenting symptoms

Answer 10

Weakness and fatigue

Question 11

The leading cause of death in patients with HCL

Answer 11

Infection

Question 12

CBC features of HCL

Answer 12

Pancytopenia
Monocytopenia

Reflecting impaired hematopoiesis caused by marrow infiltration and splenic sequestration

Question 13

Hairy cells are positive for this enzyme; In the past this was used as cytochemical staining for HCL

Answer 13

Tartrate-resistant acid phosphatase (TRAP)

Question 14

Immunophenotype of HCL

Answer 14

Strongly positive for CD20 and are positive for CD11c+, CD25+, CD103+, and CD123+

Negative for CD5−, CD10−, CD27−, and CD43−

Hairy cells demonstrate moderate to high side scatter (SC) characteristics, resulting in their shift on flow plots into the region typically occupied by monocytes.

Question 15

BMA finding in HCL

Answer 15

Marrow fibrosis is characteristic of this disease leading to a “dry” marrow aspirate

Severely hypocellular marrow

Mononuclear cells with non-overlapping cellular borders “fried egg–like” appearance

Question 16

IHC stains used in BMA to diagnose HCL

Answer 16

• anti-CD20
• Annexin
• DBA.44
• BRAF V600E

Question 17

TRUE OR FALSE

Before treatment, include an assessment of renal function as both of the commonly used purine nucleoside analogues are excreted by a renal route.

Answer 17

TRUE

Before treatment, include an assessment of renal function as both of the commonly used purine nucleoside analogues are excreted by a renal route.

Question 18

Laboratory tests useful in patient monitoring

Answer 18

• Serial complete blood count
• Soluble interleukin-2 (IL-2) receptor
• Soluble CD22

Question 19

Approximately 10% of HCL-c

Characterized by leukocytosis, lack of monocytopenia, and neoplastic B cells with nucleoli and convoluted nuclei.

Answer 19

HCL-v

Question 20

Immunophnotype of HCL-v

Answer 20

CD25− and CD123− negative, annexin-1 negative, and negative for TRA

BRAF V600E mutation is not present

Question 21

TRUE OR FALSE

HCL-v achieve durable responses with purine analogues as monotherapy.

Answer 21

FALSE

HCL-v do not achieve durable responses with purine analogues as monotherapy but may respond to combined therapies with a purine analogue and a monoclonal antibody.

Question 22

The malignant cells in the blood are characterized by cytoplasmic villi or projections that are typically polar in distribution

Answer 22

Splenic marginal zone lymphoma/splenic marginal zone lymphoma with villous lymphocytes

Although the cells are positive for CD20, they are negative for CD25, annexin 1, and usually CD103

White pulp splenic involvement

Question 23

An uncommon lymphoma that infiltrates the splenic red pulp in a diffuse pattern.

Answer 23

Splenic diffuse red pulp small B-cell lymphoma

The immunophenotypic profile shows strong expression of CD20 and negative staining for CD25, CD123, and annexin.

Question 24

Criteria for initiation of treatment in HCL

Answer 24

Symptoms related to the disease or
Deterioration in blood counts

• Absolute neutrophil count <1000/μL
• Hemoglobin <11 g/dL
• Platelet count <100,000/μL

Question 25

Approved for initial therapy of HCL

Answer 25

Cladribine

Question 26

Approved for second-line therapy of HCL

Answer 26

Pentostatin

If it is not possible to control infection, initiating treatment with reduced-dose pentostatin should be considered to secure a durable response before using standard-dose purine analogs.

Question 27

Dosing of Cladribine

Answer 27

• IV infusion 0.1 mg/kg/day for 7 days as a single course OR
• Daily IV infusion 0.14 mg/kg/day over 2 hours each day for 5 days.

Subcutaneous administration of cladribine has also been successful and may be more convenient.

Question 28

When to perform a marrow biopsy after Cladribine therapy to determine the quality of the response

Answer 28

4–6 months after blood count recovery

• 3-5 months

Question 29

Dosing of Pentostatin

Answer 29

4 mg/m2 IV every 2 weeks

Administered once every 2 weeks as a short IV injection followed by administration of approximately 1 L of fluid

Question 30

When to perform a marrow biopsy after Pentostatin therapy to determine the quality of the response

Answer 30

When the blood counts and the spleen have returned to normal

At the time of best clinical response

If there are no visible areas of HCL by morphologic criteria, then two additional doses are usually administered as consolidation.

Question 31

This drug is an inhibitor of BRAFV600E and has been shown to induce remission in relapsed or refractory HCL-c patients but is currently still “off-label”

Answer 31

Vemurafenib

Question 32

Clinical approach for resistant hairy cell leukemia

Answer 32

• Combined chemoimmunotherapy (eg, purine analogue and rituximab)
• Immunotoxin conjugates (eg, moxetumomab pasudotox (HA22)
• BRAF V600E inhibitors (eg, vemurafenib)

Question 33

The expression of which protein correlates with tumor burden and is a useful laboratory value in terms of disease monitoring?

Answer 33

Soluble interleukin 2 receptor

Soluble CD22 also can be followed in a similar manner as a correlate of leukemic cell burden. (but not yet indicated as important to monitor as response marker)

Question 34

Defined as evidence of leukemic cells on the marrow biopsy that can be detected using IHC staining when there is no residual morphologic evidence of disease

Answer 34

MRD

Question 35

TRUE OR FALSE

In general, if the patient achieved an initial response and subsequently relapses within 1–2 years, an alternate agent might be selected for retreatment.

Answer 35

TRUE

In general, if the patient achieved an initial response and subsequently relapses within 1–2 years, an alternate agent might be selected for retreatment.

In contrast, retreatment with the initial therapy can be considered if the first remission was durable.

Question 36

An immunotoxin conjugate directed against CD22, has been approved by the FDA for the treatment of patients with HCL who have failed to respond to standard therapy

Answer 36

Moxetumomab pasudotox