title: Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia.
abstract: 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.
authors.affiliation: Third Medical Department, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Hopfinger
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Natali
authors.initials: N
authors.lastname: Pflug
authors.forename: Nicole
authors.initials: N
authors.lastname: Weit
authors.forename: Anne
authors.initials: A
authors.lastname: Westermann
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Fink
authors.forename: Paula
authors.initials: P
authors.lastname: Cramer
authors.forename: Nina
authors.initials: N
authors.lastname: Reinart
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Günter
authors.initials: G
authors.lastname: Fingerle-Rowson
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kandler
authors.forename: Barbara
authors.initials: B
authors.lastname: Eichhorst
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Marco
authors.initials: M
authors.lastname: Herling
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015461:Leukemia, Prolymphocytic, T-Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D012074:Remission Induction; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine