Outcome of therapy-related myeloid neoplasms treated with azacitidine

Luana Fianchi,Pietro Leoni,Giuseppe Leone,Pellegrino Musto,Gianluca Gaidano,Marianna Criscuolo,Stefan Hohaus,Massimo Breccia,Alessandro Levis,Maria Teresa Voso,Esther N Oliva,Carlo Finelli,Antonietta Aloe Spiriti,Valeria Santini,Livio Pagano,Francesco D’Alò,Monia Lunghi

doi:10.1186/1756-8722-5-44

Abstract

BackgroundTherapy-related myeloid neoplasms (t-MN), including myelodysplastic syndromes and acute myeloid leukemia (t-MDS and t-AML) are associated to clinical and biologic unfavorable prognostic features, including high levels of DNA methylation.MethodsWe retrospectively evaluated 50 t-MN patients (34 MDS and 16 AML) selected among all patients receiving azacitidine (AZA) at 10 Italian Hematology Centers. Patients had developed a t-MN at a median of 6.5 years (range 1.7- 29) after treatment of the primary tumor (hematological neoplasm, 27 patients; solid tumor, 23 patients).ResultsThe overall response rate was 42% (complete remission: 10 patients, partial remission: 2 and hematological improvement: 8 patients) and was obtained after a median of 3 cycles (range 1–6). Median overall survival (OS) was 21 months (range 1–53.6+) from AZA start. OS was significantly better in patients with less than 20% blasts, in normal karyotype t-AML and when AZA was used as front-line treatment. This was confirmed by the multivariate analysis.ConclusionsThis study reports efficacy of AZA in the largest series of therapy-related MN patients treated with 5-AZA. Our data show that blasts and karyotype maintain their important prognostic role in t-MN also in the azacitidine era.

Highlights

Therapy-related myeloid neoplasms (t-MN), including myelodysplastic syndromes and acute myeloid leukemia (t-MDS and t-AML) are associated to clinical and biologic unfavorable prognostic features, including high levels of DNA methylation
Therapy-related myeloid neoplasms (t-MN) have been recognized as a clinical and biological distinct entity in the 2008 WHO AML classification [1]. These diseases occur after cytotoxic treatment for a primary cancer or after immunosuppressive treatment. t-MN account for about 10% of all AML, and may arise from few months to several years after the primary tumor, depending on type of cytotoxic treatment, cumulative dose and dose-intensity [2,3]
Criteria for AZA treatment were: diagnosis of t-MN according to the WHO classification, defined as leukemias occurring in patients with a history of prior cytotoxic treatment for a primary tumor

Summary

Introduction

Therapy-related myeloid neoplasms (t-MN), including myelodysplastic syndromes and acute myeloid leukemia (t-MDS and t-AML) are associated to clinical and biologic unfavorable prognostic features, including high levels of DNA methylation. Therapy-related myeloid neoplasms (t-MN) have been recognized as a clinical and biological distinct entity in the 2008 WHO AML classification [1]. By definition, these diseases occur after cytotoxic treatment for a primary cancer or after immunosuppressive treatment. Allogeneic HSCT is the only curative option, but it is not feasible in the majority of patients and is often complicated by high transplantation-related mortality rates [10]. Response rates similar to de novo AML have been recently obtained only for t-AML patients carrying t(15;17) or t(8;21) translocations and included in standard protocols [5]

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Results

Conclusion