Azacitidine-Etoposide-Cytosine Arabinoside Combination Therapy In Older Acute Myeloid Leukemias

INTRODUCTION: Acute myeloid leukemia (AML) is a hematological malignancy that affects the older population. Low intensive therapies and the best supportive care are considered better options for frail and older patients. In last decades treatment approaches have been hopefull with the hypomethylating agents for this population. The aim of this study is to investigate the efficacy of combination therapy including azacytidine (AZA), etopocide and cytosine arabinoside(Ara-C), which is used as standard care for unfit and older AML cases in our hematology department.
METHODS: Retrospectively, we analyzed our newly-diagnosed older AML patients who were ineligible for intensive regimens due to unfit performance status. Groups with similar age, ECOG performance status and comorbidity were compared in terms of hematological parameters, follow-up, response status and survival. While 32 patients were treated with a combined hypomethylating agent protocol, other patients (n: 32) received low intense therapy including low dose Ara-C and/or daily hydroxyurea (HU).
RESULTS: Eight patients who treated with combined protocol achieved complet remission and parsial remission least. (p: 0.011) While 30 day-mortality was found significantly higher in patients treated with the low intense therapy than AZA combined protocol, overall survival was found similar (resp. p: 0.005 and p: 0.092).
DISCUSSION AND CONCLUSION: Treatment should be encouraged for older AML patients who are not eligible for intensive therapy due to comorbidities and poor performance. While combinations of HMA with new investigational therapies are promising strategies, there is a need for the investigation of new combinations of HMA with easily accessible agents for developing countries where expensive new agents are not available. With the survival and response advantage, AZA-etopocide-AraC combination therapy can be a treatment option for selected patients.

Yaþlý Akut Myeloid Lösemi Hastalarýnda Azasitidin-Etoposid-Sitozin Arabinozid Kombinasyon Terapisi

GÝRÝÞ ve AMAÇ: Akut myeloid lösemi(AML) yaþlý populasyonda sýklýðý artan hematolojik malignitedir. Düþkün ve yaþlý hastalarda düþük yoðunluktaki tedaviler ve destek tedavisi uygun seçenekler olarak öngörülmektedir. On yýllarda hipometile edici ajanlarýn kullanýmý ile tedavi alanýnda olumlu geliþmeler yaþanmýþtýr. Çalýþmamýzýn amacý merkezimizde ileri yaþ AML hastalarýmýzda tedavi protokolu olarak uyguladýðýmýz etoposit ve sitozin arabinozid(AraC) ile güçlendirilmiþ azasitidin(AZA) kombinasyon rejiminin etkinliðini araþtýrmaktýr.
YÖNTEM ve GEREÇLER: Takip ettiðimiz ileri yaþta ve performans durumu nedeni ile yoðun tedaviler için uygun olmayan yeni taný AML hastalarý retrospektif olarak incelenmiþtir. Yaþ, performans durumu, komorbidite açýsýndan benzer iki grup oluþturulmuþ, bir grup (n: 32) AZA-etoposit-AraC kombinasyonu ile tedavi edilirken, diðer grup (n: 32) düþük doz sitozin arabinozid ve/veya hydroksiüre ile tedavi edilmiþtir. Gruplar kendi aralarýnda hematolojik parametreler, takip süresi, yanýt durumu ve sað kalým açýsýndan karþýlaþtýrýlmýþtýr.
BULGULAR: Azasitidin kombinasyonu ile tedavi edilen sekiz hastada tam yanýt veya enaz parsiyel yanýt elde edilmiþtir (p: 0.011). 30 günlük mortalite düþük yoðunluklu tedavi kolunda anlamlý olarak yüksek saptanýrken, toplam sað kalým açýsýndan her iki grupta farklýlýk saptanmamýþtýr (sýrasýyla p: 0.005 and p: 0.092)
TARTIÞMA ve SONUÇ: Yoðun tedavileri alamayan, ileri yaþ ve düþkün hastalar tedavi edilme açýsýndan cesaretlendirilmelidir. Özellikle geliþmekte olan ülkelerde, hipometile edici ilaçlarla pahalý ve ulaþýlmasý zor moleküllerin kombinasyonlarýnýn yanýsýra ucuz ve eriþimi kolay moleküllerin kombinasyonlarýna ihtiyaç vardýr. Yanýt avantajý saðlayan azasitidin-etoposit-sitozin arabinozid kombinasyon tedavisini seçili hastalarda uygulanmasýný öneriyoruz.