BACKGROUND: Scarce systematic trial data have prevented uniform therapeutic 
guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this 
historically refractory tumor is the controlled evaluation of multiagent 
chemotherapy and its combination with the currently most active single agent, 
alemtuzumab.
METHODS: This prospective multicenter phase 2 trial assessed response, survival, 
and toxicity of a novel regimen in previously treated (n = 9) and 
treatment-naive (n = 16) patients with T-PLL. Induction by fludarabine, 
mitoxantrone, and cyclophosphamide (FMC), for up to 4 cycles, was followed by 
alemtuzumab (A) consolidation, up to 12 weeks.
RESULTS: Of the 25 patients treated with FMC, 21 subsequently received 
alemtuzumab. Overall response rate to FMC was 68%, comprising 6 complete 
remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab 
consolidation increased the intent-to-treat overall response rate to 92% (12 
complete remissions; 11 partial remissions). Median overall survival after FMC-A 
was 17.1 months and median progression-free survival was 11.9 months. 
Progression-free survival tended to be shorter for patients with high-level 
T-cell leukemia 1 oncoprotein expression. Hematologic toxicities were the most 
frequent grade 3/4 side effects under FMC-A. Exclusively in the 21 
alemtuzumab-consolidated patients, 13 cytomegalovirus reactivations were 
observed; 9 of these 13 represented a clinically relevant infection.
CONCLUSIONS: FMC-A is a safe and efficient protocol in T-PLL, which compares 
favorably to published data.