The present disclosure relates to the field of combination therapy for treatment of hematological malignancy selected from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The disclosure provides a combination therapy comprising plant based compounds and hypomethylating agent (HMA). Particularly, the disclosure provides a combination of: a) a therapeutically effective amount of a combination comprising sulforaphane, resveratrol and curcumin; and b) a therapeutically effective amount of HMA selected from azacitidine (AZA), decitabine (DEC) and a combination thereof, for treating MDS or AML. Said combination provides an enhanced/synergistic effect in the treatment of MDS or AML along with decreasing or overcoming resistance to HMA (azacitidine or decitabine). Methods for decreasing or overcoming resistance to HMA (azacitidine or decitabine), corresponding use of the above described combination and a kit comprising said combination are also provided.