| Literatürler Hematoloji Uzmanlık Derneği
Literatür Detay Bilgisi
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase II trial.

Yazarlar : Braun T, Itzykson R, Renneville A, de Renzis B, Dreyfus F, Laribi K, Bouabdallah K, Vey N, Toma A, Recher C, Royer B, Joly B, Vekhoff A, Lafon I, Sanhes L, Meurice G, Oréar C, Preudhomme C, Gardin C, Ades L, Fontenay M, Fenaux P, Droin N, Solary E.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21828134

Konu : Lösemi

Literatür İçeriği :  

Abstract

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 II trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial (Wattel et al. Blood 1997). 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 (HI, 8%). Eighteen patients (46%) demonstrated stable disease without HI, and 6 (15%) progressed to acute leukemia. With a median follow up of 23 months, overall survival (OS) was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and JAK2 genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival upon DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in about 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.


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