Background
Long-term single-institution series of cladribine (2-CdA) monotherapy in Hairy Cell Leukemia (HCL). N=207 consecutive previously untreated HCL patients at a single Italian center. Cladribine (2-chlorodeoxyadenosine), a purine analog, has high single-agent activity in HCL, inducing durable complete remissions. One of the largest series establishing cladribine as the historical standard frontline therapy for HCL. Published Blood Cancer Journal 2022.
Interventions and follow up
Regimen: Cladribine (2-CdA) 0.1 mg/kg/day continuous IV infusion × 7 days (single course) — treatment-naïve classic hairy-cell leukemia
Primary endpoint: CR rate, relapse-free survival, overall survival
mFollow up: ~14 years
Primary endpoint: CR rate, relapse-free survival, overall survival
mFollow up: ~14 years
Results
CR rate (initial): 76%
ORR: 97%
10-yr RFS: 47%
15-yr RFS: 35%
20-yr OS: 87%
Median time to first relapse: ~9.5 years
CR to cladribine re-treatment at first relapse: 55%
ORR: 97%
10-yr RFS: 47%
15-yr RFS: 35%
20-yr OS: 87%
Median time to first relapse: ~9.5 years
CR to cladribine re-treatment at first relapse: 55%
Adverse events
Hematologic: Grade ≥3 neutropenia 60%; prolonged lymphopenia (CD4+ nadir months 2–4, recovery over 1–2 years)
Infections: Grade ≥3 infections 20% (most in first 2 months); fever any grade 30%
Other: Rare secondary malignancies (solid and hematologic, long-term); no treatment-related mortality in this series
Infections: Grade ≥3 infections 20% (most in first 2 months); fever any grade 30%
Other: Rare secondary malignancies (solid and hematologic, long-term); no treatment-related mortality in this series
Conclusions
A single 7-day course of cladribine achieved a 76% CR rate and 97% ORR in treatment-naive HCL, with 87% OS at 20 years, confirming cladribine as a highly effective frontline therapy for HCL. About half of patients remain relapse-free at 10 years, and re-treatment at relapse remains effective.
Key Limitations
Retrospective single-center series: No randomized comparator; referral and treatment-era heterogeneity
Late relapses: Continued relapse beyond 10–15 years means RFS curves do not plateau
No MRD assessment: Predates routine uMRD/flow endpoints, limiting depth-of-response data
Late relapses: Continued relapse beyond 10–15 years means RFS curves do not plateau
No MRD assessment: Predates routine uMRD/flow endpoints, limiting depth-of-response data
Clinical Context
Purine analogs (cladribine, pentostatin) remain the frontline standard for symptomatic classic HCL. The addition of rituximab to cladribine deepens responses and improves uMRD-negative CR rates (Chihara/Ravandi data) and is increasingly used. For multiply-relapsed/refractory disease, BRAF-targeted therapy (vemurafenib ± rituximab, dabrafenib+trametinib), moxetumomab pasudotox, and venetoclax-based regimens are options.