Chapter 21: Leukemia, Hairy Cell

Epidemiology

Pathology

Peripheral blood findings at diagnosis

1. Pancytopenia: 50%

2. “Leukemic” phase with a WBC >1000/mm³: 10–20%

3. Monocytopenia

4. Hairy cells identified in most patients, but the number is usually low and may be difficult to identify in the peripheral blood because of low numbers and staining technique

Bone marrow findings at diagnosis

1. Hypercellularity

2. Hairy cell infiltration: diffuse, patchy, or interstitial

   Diffuse infiltration: Often results in complete effacement of bone marrow

   Patchy infiltration: Subtle small clusters of hairy cells present focally or throughout the bone marrow

   Interstitial Infiltration: Hairy cells do not form well-defined discreet aggregates, but merge almost imperceptibly with surrounding normal hematopoietic tissue

3. Hairy cell nuclei are usually round, oval, or indented, and are widely separated from each other by abundant, clear or lightly eosinophilic cytoplasm. Rarely hairy cells can be convoluted or spindle shaped

4. Extravasated blood cells create blood lakes in the bone marrow similar to those observed in the spleen

5. Mast cells are often numerous

6. Reticulin stain of the bone marrow almost always shows moderate to marked increase in reticulin fibers

7. Approximately 10–20% of patients show a hypocellular bone marrow

Immunophenotyping, cytogenetics, and molecular diagnostic studies

1. Cytochemical studies: Tartrate-resistant acid phosphatase (TRAP) stain. However, TRAP is not specific for HCL

2. Hairy cell immunophenotype: CD19(+), CD20(+), CD22(+), CD79B(+), CD5(−), CD10(−), CD11C(+), CD25 Sub(+), FMC(+), CD103(+), CD45(+)

3. Clonal cytogenetics: Abnormalities in approximately two-thirds of patients. Chromosomes 1, 2, 5, 6, 11, 14, 19, and 20 are most frequently involved. Chromosome 5 is altered in approximately 40%, most commonly as a trisomy 5, pericentric inversion, and interstitial deletions involving band 5q13. However, the identification of cytogenetic abnormalities in a patient with a definite diagnosis of HCL is usually not important as it does not influence, as far as is currently determined, prognosis or therapy

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Work-up

1. H&P

2. CBC with differential, serum electrolytes, BUN, creatinine, LFTs, and uric acid

3. Bone marrow aspirate and biopsy for tartrate-resistant acid phosphatase (TRAP) (although TRAP is not required for the diagnosis, has been largely abandoned, and has been supplanted by immunophenotyping) and morphologic review; immunophenotyping by flow cytometry with B-cell–associated antibodies, including CD20, CD79A, or DBA.44

Tallman MS et al. Hairy cell leukemia. In: Hoffman, ed. Hematology: Basic Principles and Practice, 3rd ed. Philadelphia, Churchill Livingstone, 2000:1363–1372

Differential Diagnosis

Other small B-cell lymphoproliferative disorders associated with splenomegaly:

1. Prolymphocytic leukemia

   1. Marked elevation in the WBC

   2. Characteristic morphology of the prolymphocytes

   3. Different immunophenotypic profile

2. Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes)

   1. Cells do not usually exhibit TRAP positivity

   2. Bone marrow infiltrates are demarcated sharply

   3. Different immunophenotypic profile; CD103(−)

3. HCL variant

   1. Morphologic features between hairy cells and prolymphocytes

   2. Usually associated with leukocytosis/lack of monocytopenia

   3. Absence of CD25 expression

4. Systemic mastocytosis

   1. Mast cells are negative for B-cell markers, and positive for tryptase

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Prognosis

Regimen: Cladribine (2-Chloro-2′-Deoxyadenosine, 2-CDA)

Chacko J et al. Br J Haematol 1999;105:1145–1146

Cheson BD et al. J Clin Oncol 1998;16:3007–3015

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Cladribine 0.1 mg/kg per day; administer by continuous intravenous infusion in 100–500 mL 0.9% sodium chloride injection, (0.9% NS), over 24 hours for 7 consecutive days (total dosage/cycle = 0.7 mg/kg)

or

Cladribine 0.14 mg/kg per day; administer intravenously in 100–500 mL of 0.9% NS over 2 hours for 5 consecutive days (total dosage/cycle = 0.7 mg/kg)

or

Cladribine 0.15 mg/kg per dose; administer intravenously in 100–500 mL 0.9% NS over 3 hours once weekly for 6 consecutive weeks (total dosage/cycle = 0.9 mg/kg)

Chacko J et al. Br J Haematol 1999;105:1145–1146

Lauria F et al. Blood 1997;89:1838–1839

Supportive Care

Antiemetic prophylaxis

See Chapter 39 for antiemetic recommendations

Emetogenic potential is MINIMAL

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is not indicated

Antimicrobial prophylaxis

Risk of fever and neutropenia is INTERMEDIATE

  Antimicrobial primary prophylaxis is not clearly indicated. However, the following can be considered:

• Antibacterial—consider a fluoroquinolone during neutropenia or

• Antifungal—consider use during neutropenia

• Antiviral—antiherpes antivirals (eg, acyclovir) as patients may develop herpes viral infections as a result of their underlying disease even without the influence of purine analog therapy

See Chapter 47 for more information

Optional: Allopurinol 300 mg/day; administer orally, beginning on the first day of cladribine administration and continue for 2 weeks. Tumor lysis is uncommon and allopurinol need not be routinely administered. In addition, cutaneous disorders have occasionally been reported when cladribine used with allopurinol

Therapy Monitoring

1. Every other day for the week of therapy, then weekly for the next 7 weeks: CBC and serum electrolytes, BUN, creatinine, LFTs, and uric acid

2. Three months after the completion of therapy: Bone marrow aspirate and biopsy

3. Long-term follow-up: CBC every 3–6 months for 2 years, and then every 6 months for 3 years

Treatment Modifications

Patient Population Studied

Patients with newly diagnosed as well as relapsed and refractory disease

Efficacy

Toxicity (N = 895)

Notes

Cladribine may be administered to patients with relapsed or refractory disease

Regimen: Pentostatin (2′-Deoxycoformycin, DCF)

Grever M et al. J Clin Oncol 1995;13:974–982

Hydration: 5% Dextrose/0.9% sodium chloride injection or 5% dextrose/0.45% sodium chloride injection; administer intravenously 1000 mL before and at least 500 mL after pentostatin administration

Pentostatin 4 mg/m²; administer intravenously over 20–30 minutes in 25–50 mL 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) every 2 weeks until complete remission (total dosage per 2-week course = 4 mg/m²)

then

Pentostatin 4 mg/m²; administer intravenously over 20–30 minutes in 25–50 mL 0.9% NS or D5W every 2 weeks for 2 courses (total dosage per 2-week course = 4 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential is MINIMAL

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis should be considered in patients with:

ANC <500/mm³ or in patients with history of recurrent episodes of fever and neutropenia

 Pegfilgrastim (pegylated filgrastim) 6 mg/0.6 mL by subcutaneous injection for 1 dose

• Begin use from 24–72 hours after myelosuppressive chemotherapy is completed

Antimicrobial prophylaxis

Risk of fever and neutropenia is INTERMEDIATE

 Antimicrobial primary prophylaxis is not clearly indicated

• Antibacterial—no prophylaxis

• Antifungal—no prophylaxis

• Antiviral—antiherpes antivirals (eg, acyclovir) as patients may develop herpes viral infections as a result of their underlying disease even without the influence of purine analog therapy

Allopurinol: Tumor lysis is uncommon and allopurinol need not be routinely administered

Patient Population Studied

Study of 154 patients with previously untreated hairy cell leukemia

Efficacy

Toxicity (N = 154)

Treatment Modifications

Therapy Monitoring

1. Two to 3 times per week during therapy: CBC and serum electrolytes, BUN, creatinine, LFTs, and uric acid

2. Three months after the completion of therapy: Bone marrow aspirate and biopsy

3. Long-term follow-up: CBC every 3–6 months for 2 years, and then every 6 months for 3 years

Regimen: Rituximab

Hagberg H, Lundholm L. Br J Haematol 2001;115:609–611

Lauria F et al. Haematologica 2001;86:1046–1050

Nieva J et al. Blood 2003;102:810–813

Premedication:

1. Acetaminophen 650–1000 mg; administer orally, 30–60 minutes before rituximab

2. Diphenhydramine 25–50 mg; administer orally or by intravenous injection 30–60 minutes before rituximab

Rituximab 375 mg/m² per week; administer intravenously in 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) diluted to a concentration within the range of 1–4 mg/mL for 4 consecutive weeks (total dosage per 4-week course = 1500 mg/m²)

or

Rituximab 375 mg/m² per week; administer intravenously in 0.9% NS or D5W diluted to a concentration within the range of 1–4 mg/mL for 8 consecutive weeks with an additional 4 weekly doses (maximum of 12 doses) if a patient does not achieve a complete remission, but shows signs of continual improvement (total dosage per 8-week and 12-week courses = 3000 mg/m² and 4500 mg/m², respectively)

Thomas DA et al. Blood 2003;102:3906–3911

Rituximab infusion rates:

First dose: Start at an initial rate of 50 mg/hour. If hypersensitivity or infusion reactions do not occur during the first 30 minutes, increase the rate by 50 mg/hour every 30 minutes, to a maximum rate of 400 mg/hour

Subsequent doses: If previous administration was well tolerated, start at 100 mg/hour, and, if tolerated, increase by 100 mg/hour every 30 minutes, to a maximum rate of 400 mg/hour

Supportive Care

Antiemetic prophylaxis

Emetogenic potential is MINIMAL

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is NOT indicated

See Chapter 43 for more information

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

  Antimicrobial primary prophylaxis to be considered:

• Antibacterial—P. jirovecii prophylaxis is recommended (eg, cotrimoxazole)

• Antifungal—not indicated

• Antiviral—not indicated, unless patient previously had an episode of HSV

See Chapter 47 for more information

Optional: Allopurinol 300 mg/day; administer orally, beginning on the first day of rituximab administration and continuing for 2 weeks. Tumor lysis is uncommon and allopurinol need not be routinely administered

Patient Population Studied

Relapsed or refractory HCL

Efficacy

Toxicity (N = 15)

Therapy Monitoring

1. Weekly prior to each dose of rituximab: CBC

2. One to 3 months after the completion of therapy: Bone marrow aspirate and biopsy with immunophenotyping

3. Long-term follow-up: CBC every 3–6 months for 2 years, and then every 6 months for 3 years

Treatment Modifications

Fever, chills, hypotension, and other toxicities:

Slow or interrupt rituximab administration

Severe hypersensitivity reactions:

1. Interrupt administration

2. Diphenhydramine 25–50 mg; administration by intravenous injection is recommended

3. Additional treatment with diphenhydramine, bronchodilators, intravenous hydrocortisone, and/or intravenous hydration may be indicated

4. Resume infusion at a 50% reduction in rate when symptoms have completely resolved

5. Medications for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction during administration (eg, intravenous fluids, epinephrine, antihistamines, glucocorticoids, and O₂)

6. In many cases, the infusion can be resumed at a 50% reduction in rate when symptoms have completely resolved