Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial

被引：179

作者：

Braun, Thorsten ^{[3
]}

Itzykson, Raphael ^{[1
,2
,3
]}

Renneville, Aline ^{[4
]}

de Renzis, Benoit ^{[5
]}

Dreyfus, Francois ^{[6
]}

Laribi, Kamel ^{[7
]}

Bouabdallah, Krimo ^{[8
]}

Vey, Norbert ^{[9
]}

Toma, Andrea ^{[10
]}

Recher, Christian ^{[11
]}

Royer, Bruno ^{[12
]}

Joly, Bertrand ^{[13
]}

Vekhoff, Anne ^{[14
]}

Lafon, Ingrid ^{[15
]}

Sanhes, Laurence ^{[16
]}

Meurice, Guillaume ^{[1
,2
]}

Orear, Cedric ^{[1
,2
]}

Preudhomme, Claude ^{[4
]}

Gardin, Claude ^{[3
]}

Ades, Lionel ^{[3
]}

Fontenay, Michaela ^{[17
]}

Fenaux, Pierre ^{[3
]}

Droin, Nathalie ^{[1
,2
]}

Solary, Eric ^{[1
,2
]}

机构：

[1] Inst Gustave Roussy, INSERM, UMR 1009, F-94805 Villejuif, France

[2] Univ Paris 11, Villejuif, France

[3] Univ Paris 13, Hop Avicenne, AP HP, Hematol Clin, Bobigny, France

[4] Univ Lille, CHU Lille, Lille, France

[5] CHU Estaing, Hematol Clin Adulte & Therapie Cellulaire, Clermont Ferrand, France

[6] Univ Paris 05, Hop Cochin, AP HP, Paris, France

[7] Ctr Hosp CH Mans, Le Mans, France

[8] Univ Bordeaux, Hop Haut Leveque, Bordeaux, France

[9] Inst Paoli Calmette, Dept Hematol, Marseille, France

[10] Univ Paris 12, Hop Henri Mondor, AP HP, Hematol Clin, F-94010 Creteil, France

[11] Univ Toulouse 3, CHU Toulouse, Hop Purpan, CNRS,INSERM,UMR 1037,Canc Res Ctr Toulouse,ERL 52, F-31062 Toulouse, France

[12] Univ Amiens, CHU Amiens, Serv Hematol Clin, Amiens, France

[13] CH Sud Francilien, Hematol Clin, Corbeil Essonnes, France

[14] Univ Paris 04, Hop St Antoine, AP HP, Hematol Clin, Paris, France

[15] Univ Burgundy, CHU Le Bocage, Hematol Clin, Dijon, France

[16] CH Perpignan, Hematol Clin, Perpignan, France

[17] Univ Paris 05, Grp Hosp GH Broca Cochin Hotel Dieu, AP HP, INSERM,Inst Cochin,U1016,CNRS,UMR 8104, Paris, France

来源：

BLOOD | 2011年 / 118卷 / 14期

关键词：

RISK MYELODYSPLASTIC SYNDROMES; ACUTE MYELOID-LEUKEMIA; PROGNOSTIC-FACTORS; MYELOPROLIFERATIVE NEOPLASMS; C-JUN; MUTATIONS; GENE; AZACITIDINE; FREQUENT; TET2;

D O I：

10.1182/blood-2011-05-352039

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1 gamma, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract. ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084. (Blood. 2011;118(14):3824-3831)

引用

页码：3824 / 3831

页数：8

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