What are non-clinical trial options to treat high-risk MDS in a transplant ineligible patient, after progression on hypomethylating agents?

This is often a difficult discussion to have with patients as there are currently no FDA approved second line treatment approaches for such patients, but this remains an active area for clinical investigation. Some approaches are nicely reviewed in Dr. Santini's 2019 How I Treat article in Blood.

In my own experience, I typically repeat NGS studies on the bone marrow aspirate to search for potentially actionable mutations, such as IDH1/IDH2 or FLT3, and try to obtain insurance approval to treat w...

The nucleoside analog decitabine has a molecular-targeted action of depleting DNA methyltransferase 1 (DNMT1) which occurs at low concentrations separate from its cytotoxic effect. Regular decitabine doses/concentrations cause cytotoxic effects and they limit feasible exposure times for this DNMT1 depleting molecular effect to occur which can cytoreduce p53-null, chemorefractory myeloid malignancies via terminal-differentiation instead of apoptosis, simultaneously sparing normal hematopoiesis. D...