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.
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Authors | Georg Hopfinger, Raymonde Busch, Natali Pflug, Nicole Weit, Anne Westermann, Anna-Maria Fink, Paula Cramer, Nina Reinart, Dirk Winkler, Günter Fingerle-Rowson, Stephan Stilgenbauer, Hartmut Döhner, Gabriele Kandler, Barbara Eichhorst, Michael Hallek, Marco Herling |
Journal | Cancer
(Cancer)
Vol. 119
Issue 12
Pg. 2258-67
(Jun 15 2013)
ISSN: 1097-0142 [Electronic] United States |
PMID | 23512246
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
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Copyright | Copyright © 2013 American Cancer Society. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Proto-Oncogene Proteins
- TCL1A protein, human
- Alemtuzumab
- Cyclophosphamide
- Mitoxantrone
- Vidarabine
- fludarabine
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Topics |
- Adult
- Aged
- Alemtuzumab
- Antibodies, Monoclonal, Humanized
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Chromosome Aberrations
- Cyclophosphamide
(administration & dosage)
- Disease-Free Survival
- Female
- Humans
- Leukemia, Prolymphocytic, T-Cell
(drug therapy, genetics, mortality)
- Male
- Middle Aged
- Mitoxantrone
(administration & dosage)
- Proto-Oncogene Proteins
(analysis, metabolism)
- Remission Induction
- Treatment Outcome
- Vidarabine
(administration & dosage, adverse effects, analogs & derivatives)
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