What are the treatment options and common causes of mortality for hairy cell leukemia?

Hairy Cell Leukemia: Characteristics and Treatment

Hairy cell leukemia is an indolent B-cell leukemia where death is usually related to infectious complications, not an aggressive T-cell leukemia, and cannot be cured with splenectomy.

Disease Characteristics

Hairy cell leukemia (HCL) is characterized by:

• A chronic, indolent B-cell lymphoproliferative disorder 1
• Distinctive immunophenotype: CD5-, CD10-, CD11c+, CD20+ (bright), CD22+, CD25+, CD103+, CD123+, cyclin D1+, annexin A1+, and CD200+ (bright) 1
• Presence of BRAF V600E mutation in classic HCL (distinguishes it from HCL variant) 1
• Splenomegaly as a common clinical feature 1
• Pancytopenia with monocytopenia 1

Treatment Options

First-Line Treatment

• Purine nucleoside analogs (cladribine or pentostatin) are the standard first-line treatment for symptomatic HCL patients 1, 2
• Cladribine induces durable responses in 87-100% of patients, with complete response rates of 85-91% after a single course 1, 2
• Cladribine administration options:
  • Continuous IV infusion: 0.09 mg/kg/day for 7 days
  • 2-hour IV infusion: 0.12-0.14 mg/kg/day for 5 days
  • Subcutaneous injection: 0.1 mg/kg/day for 5-7 days
  • Weekly schedule: 0.12-0.15 mg/kg once weekly for 5-6 weeks 1, 2, 3

Treatment Indications

Treatment should be initiated in patients with:

• Symptomatic disease (fatigue, weight loss)
• Cytopenias (hemoglobin <10 g/dL, platelets <100 × 10^9/L, neutrophils <1 × 10^9/L)
• Symptomatic splenomegaly
• Recurrent infections 1, 2

Special Considerations

• For patients with severe neutropenia or active infection, consider:
  • Controlling infection before administering purine analogs
  • Initial therapy with interferon-α to increase neutrophil count before purine analog therapy 2
• Anti-infective prophylaxis during treatment:
  • Herpes virus prophylaxis with acyclovir
  • PJP prophylaxis with sulfamethoxazole/trimethoprim
  • Consider broad-spectrum antibacterial coverage during neutropenia 1

Response Assessment

• Formal assessment 4-6 months after completion of therapy 1, 2
• Complete response (CR): normalization of blood counts, absence of hairy cells in bone marrow and peripheral blood, regression of splenomegaly 1
• Partial response (PR): normalization of peripheral counts, ≥50% reduction in organomegaly and bone marrow hairy cells 1

Relapse and Retreatment

• If relapse occurs after >24 months, consider re-treatment with purine analog 1
• If relapse occurs after >60 months, consider re-treatment with initial therapy 1
• If relapse occurs <24 months after treatment, consider alternative therapy or investigational agents 1
• Overall response rate for second-line treatment with cladribine is approximately 83% 2, 4

Mortality and Complications

• Infections are the most frequent cause of death in HCL patients 2, 3
• During the first month of cladribine therapy, approximately two-thirds of patients develop fever, and 47% experience fever with neutropenia 3
• Fatal infections, including sepsis and pneumonia, can occur, particularly in previously treated patients 3
• Second malignancies have been reported with an observed-to-expected ratio of 1.88-2.03 4, 5

Key Points About Splenectomy

• Splenectomy is not curative for HCL 1
• While historically used as a treatment option, splenectomy has been largely replaced by purine analogs as first-line therapy 1, 2
• Splenectomy may still offer benefit in selected cases but is considered an older therapeutic approach 1

Monitoring and Follow-up

• Regular monitoring of blood counts and vigilance for infections 2
• Surveillance for second malignancies 2
• Asymptomatic patients without cytopenias should be monitored with regular follow-up every 3-6 months 2

Hairy cell leukemia is a distinct clinical entity from HCL variant (HCLv), which tends to be more aggressive and less responsive to standard therapies 1.