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Jilg, Stefanie; Hauch, Richard T.; Kauschinger, Johanna; Buschhorn, Lars; Odinius, Timo O.; Dill, Veronika; Müller-Thomas, Catharina; Herold, Tobias; Prodinger, Peter M.; Schmidt, Burkhard; Hempel, Dirk; Bassermann, Florian; Peschel, Christian; Götze, Katharina S.; Hoeckendorf, Ulrike; Haferlach, Torsten and Jost, Philipp J. (2019): Venetoclax with azacitidine targets refractory MDS but spares healthy hematopoiesis at tailored dose. In: Experimental Hematology & Oncology, Vol. 8, 9

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Abstract

Patients with Myelodysplastic Syndromes (MDS) and secondary Acute Myeloid Leukemia (sAML) have a very poor prognosis after failure of hypomethylating agents (HMA). Stem cell transplantation is the only effective salvage therapy, for which only a limited number of patients are eligible due to age and comorbidity. Combination therapy of venetoclax and azacitidine (5-AZA) seems to be a promising approach in myeloid malignancies, but data from patients with HMA failure are lacking. Furthermore, a considerable concern of combination regimens in elderly AML and MDS patients is the toxicity on the remaining healthy hematopoiesis. Here, we report in vitro data showing the impact of venetoclax and 5-AZA, alone or in combination, in a larger cohort of MDS/sAML patients (n = 21), even after HMA failure (n = 13). We especially focused on the effects on healthy hematopoiesis and the impact on colony forming capacity as a parameter for long-term effects. To the best of our knowledge, we show for the first time that venetoclax in combination with capped dose of 5-AZA targets cell malignancies, while sparing healthy hematopoiesis.

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