Management of Hairy Cell Leukemia
Purine nucleoside analogs (cladribine or pentostatin) are the first-line treatment for symptomatic hairy cell leukemia, with cladribine being the preferred agent due to its convenience of administration. 1
When to Initiate Treatment
Treatment should be initiated for patients with:
- Symptomatic disease
- Cytopenias
- Symptomatic splenomegaly or hepatomegaly
- Unexplained weight loss
- Progressive lymphocytosis or lymphadenopathy
- Recurrent infections 1
Asymptomatic patients without cytopenias should be monitored with regular follow-up every 3-6 months 1.
First-Line Treatment Options
Cladribine (Preferred Agent)
Cladribine is administered as a single course with several dosing options:
| Administration Method | Dosing Regimen | Duration |
|---|---|---|
| Continuous IV infusion | 0.09 mg/kg/day | 7 days |
| 2-hour IV infusion | 0.12-0.14 mg/kg/day | 5 days |
| Subcutaneous injection | 0.1 mg/kg/day | 5-7 days |
| Weekly schedule | 0.12-0.15 mg/kg once weekly | 5-6 weeks |
The FDA-approved regimen is continuous infusion for 7 consecutive days at 0.09 mg/kg/day 2. The drug should be diluted with 0.9% Sodium Chloride Injection (500 mL) and infused continuously over 24 hours 2.
Special Considerations
- Active Infections: Control infection before administering purine analogs; consider alternative initial therapy with interferon-α, low-dose pentostatin, or vemurafenib 1
- Severe Neutropenia: Consider interferon-α initially to increase neutrophil count before purine analog therapy 1
- Renal Insufficiency: Proceed carefully as specific risk factors for increased toxicity have not been defined 2
Response Assessment
Formal assessment should be performed 4-6 months after completion of primary therapy, including:
- Complete blood count
- Bone marrow biopsy
- Physical examination
- Imaging studies as needed 1
Response Criteria
- Complete Response (CR): Normalization of blood counts, absence of hairy cells in bone marrow and peripheral blood, and regression of splenomegaly
- Partial Response (PR): Normalization of peripheral counts, ≥50% reduction in organomegaly and bone marrow hairy cells, and <5% circulating hairy cells 1
Management of Partial Response or Relapse
- If only partial response is achieved after first course of cladribine, a second course should be repeated at least 6 months after the end of the first course, with or without rituximab 1
- Retreatment with purine analogs is effective at relapse, with an overall response rate of 83% in second-line treatment 1
- Recent evidence suggests that combining cladribine with rituximab (either concurrent or delayed) can lead to higher rates of minimal residual disease (MRD)-free complete remission 3
Monitoring and Follow-up
- Regular monitoring of blood counts is essential 1
- Vigilance for infections is critical as they are the most frequent cause of death 1
- Surveillance for second malignancies, although recent data suggests their incidence is not increased compared to the general population 1, 4
Emerging Treatment Options for Relapsed/Refractory Disease
For patients with relapsed or refractory disease:
- BRAF inhibitors (vemurafenib or dabrafenib) are emerging as an attractive chemotherapy-free strategy, particularly for patients with or at risk of severe infections 5
- Combination of BRAF inhibitors with rituximab has shown high efficacy 5
- Other treatments being explored include BTK inhibition with ibrutinib and co-inhibition of BRAF and MEK 5
Common Pitfalls and Caveats
- If the patient does not respond to the initial course of cladribine, it is unlikely they will benefit from additional courses 2
- Physicians should consider delaying or discontinuing cladribine if neurotoxicity or renal toxicity occurs 2
- Long-term follow-up data shows excellent outcomes with subcutaneous cladribine, with most patients requiring only one cycle for long-term disease control 4
- Second primary malignancies can occur (median time to occurrence 5.7 years) and are a main cause of death, though their incidence is not increased compared to the general population 4