期刊
BLOOD
卷 114, 期 21, 页码 4696-4702出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-03-212449
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类别
资金
- EHA Clinical Research
- Hairy Cell Leukemia Research Foundation
- Piano di Ateneo per la Ricerca 2005 (University of Siena)
- Cofinanziamento Ministero dell'Universitae della Ricerca per Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (MUR-PRIN)
- Associazione Italiana per la Ricerca sul Cancro
- Associazione Italiana contro le Leucemie
- Mielomi e Linfoma (Siena-AIL Section), Siena, Italy
Hairy cell leukemia (HCL) is generally responsive to single-agent cladribine, and only a minority of patients are refractory and with poor prognosis. HCLs generally express mutated ( M) and, in a minority, unmutated (UM) IGHV. In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival after single-agent cladribine. Of 58 HCLs, 6 expressed UM-IGHV (UM-HCL) and 52 M-IGHV (M-HCL). Beneficial responses were obtained in 53 of 58 patients (91%), whereas treatment failures were observed in 5 of 58 patients (9%). Failures were associated significantly with UM-IGHV ( 5 of 5 failures vs 1 of 53 beneficial responses had UM-IGHV, P < .001), leukocytosis ( 3 of 5 vs 3 of 53, P = .006), and bulky spleen ( 4 of 5 vs 4 of 53, P < .001). The UM- HCL not benefiting from cladribine characteristically had bulky spleen ( 4 of 5, 80%), leukocytosis ( 3 of 5, 60%), and TP53 defects ( 2 of 5, 40%), and progressed rapidly after first treatment ( median event-free survival, 7.5 months). Our data suggest that UM- HCLs identify the minor subgroup failing cladribine treatment and with more aggressive disease. High incidence of TP53 dysfunction indicates a potential mechanism of resistance to cladribine in the UM- HCL group. Overall, our data provide new molecular elements relevant for treatment concerns in HCL. ( Blood. 2009;114:4696-4702)
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