Multivariable analysis of MIPSS70/MIPSS70+ relevant risk variables, after the incorporation of the above-mentioned new information, identified VHR karyotype, unfavorable karyotype, ≥2 HMR mutations, presence of HMR mutation, absence of type 1/like CALR mutation, constitutional symptoms, anemia adjusted for both sex and severity, and circulating blasts ≥2% as independent risk factors for survival. This evidence concerns the gene CALR and anemia.