How I treat higher-risk MDS: I employ risk stratification by IPSS and IPSS-R. Higher-risk patients include intermediate-2 and high-risk by IPSS or high-/very high risk by IPSS-R. I favor azanucleoside-based therapy, preferably on a clinical trial, and strongly advocate early referral for allogeneic hematopoietic stem cell transplant (allo-HCT) in transplant-eligible individuals. In the case of prior azanucleoside exposure and HMA failure (defined as progression, failure to respond, or relapse after 4-6 cycles of azacitidine or 4 cycles of decitabine), I strongly recommend clinical trial enrollment.