Treatment Patterns, Outcomes and Survival Trends in T‐Cell Prolymphocytic Leukemia: A Nationwide Population‐Based Study in the Netherlands

BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive mature T-cell malignancy with limited therapeutic options. Alemtuzumab remains the backbone of therapy, and fit responders are consolidated with allogeneic stem cell transplantation (alloSCT). However, contemporary population-level outcomes remain poorly defined. METHODS: All T-PLL cases diagnosed between 2001 and 2023 were identified from the nationwide Netherlands Cancer Registry. Overall survival (OS) and survival after relapse (OS2) were analyzed in 220 patients. Detailed treatment-line data were available for patients diagnosed from 2014 onward (n = 120), enabling assessment of treatment sequencing, response, and progression-free survival (PFS). RESULTS: Median age at diagnosis was 71 years; 56% were male. Overall, 54% received systemic therapy, of whom 25% underwent transplantation. Median OS was 13.5 months; 2- and 5-year OS were 36% and 10%, with no improvement over time. Alemtuzumab was the predominant frontline therapy and was associated with higher response and survival than other regimens. Consolidation with alloSCT provided the greatest likelihood of durable disease control, although only one-third of treated patients were eligible. Survival after relapse remained poor (median OS2, 5-7 months), and later treatment lines rarely produced durable benefit. Nearly half of patients were initially managed with observation; long-term survival remained limited after progression. CONCLUSIONS: Alemtuzumab followed by alloSCT remains the most effective strategy for fit patients with T-PLL, yet long-term survival is uncommon and has not improved over two decades. High relapse rates and poor salvage outcomes underscore the need for novel targeted and immune-based approaches and optimized post-remission strategies.