Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior

被引：97

作者：

Forconi, Francesco ^{[1
]}

Sozzi, Elisa

Cencini, Emanuele

Zaja, Francesco ^{[2
]}

Intermesoli, Tamara ^{[3
]}

Stelitano, Caterina ^{[4
]}

Rigacci, Luigi ^{[5
]}

Gherlinzoni, Filippo ^{[6
]}

Cantaffa, Renato ^{[7
]}

Baraldi, Anna ^{[8
]}

Gallamini, Andrea ^{[9
]}

Zaccaria, Alfonso ^{[10
]}

Pulsoni, Alessandro ^{[11
]}

Gobbi, Marco ^{[12
]}

Tassi, Maristella

Raspadori, Donatella

Leoncini, Lorenzo ^{[13
]}

Rinaldi, Andrea ^{[14
]}

Sabattini, Elena ^{[15
]}

Bertoni, Francesco ^{[14
]}

Pileri, Stefano A. ^{[15
]}

Lauria, Francesco

机构：

[1] Univ Siena, Dipartimento Med Clin & Sci Immunol, Sez Ematol & Trapianti, AOUS, I-53100 Siena, Italy

[2] Univ Udine, Clin Ematol, Dipartimento Ric Med & Morfol, I-33100 Udine, Italy

[3] Osped Riuniti Bergamo, Unita Strutturale Complesa Ematol & Trapianto Mid, I-24100 Bergamo, Italy

[4] Azienda Osped Reggio Calabria, Div Ematol, Calabria, Italy

[5] Azienda Osped Univ, Struttura Org Dipartimentale Ematol, Florence, Italy

[6] Osped Ca Foncello, Unita Operat Ematol, Treviso, Italy

[7] Azienda Osped Pugliese Ciaccio, Unita Operat Ematol, Catanzaro, Italy

[8] Azienda Osped SS Antonio & Biagio, Div Ematol, Alessandria, Italy

[9] Osped S Croce & Carle, Unita Operat Ematol, Cuneo, Italy

[10] Osped S Maria delle Croci, Div Ematol, Ravenna, Italy

[11] Univ Roma La Sapienza, Rome, Italy

[12] Univ Genoa, Clin Ematol, Dipartimento Med Internae Specialita Med, Genoa, Italy

[13] Univ Siena, I-53100 Siena, Italy

[14] Oncol Inst So Switzerland, Expt Oncol Lab, Bellinzona, Switzerland

[15] Univ Bologna, Ist Seragnoli, Bologna, Italy

来源：

BLOOD | 2009年 / 114卷 / 21期

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; TERM-FOLLOW-UP; SOMATIC HYPERMUTATION; GENOMIC ABERRATIONS; RITUXIMAB; MUTATION; 2-CHLORODEOXYADENOSINE; IMMUNOGLOBULIN; CYTOTOXICITY; PENTOSTATIN;

D O I：

10.1182/blood-2009-03-212449

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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)

引用

页码：4696 / 4702

页数：7

共 49 条

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