Nowe strategie leczenia zespołów mielodysplastycznych wysokiego ryzyka

Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic disorders. The only treatment leading to a recovery of patients with MDS is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, a large proportion of patients is not eligible for allo-HSCT due to an advanced age, presence of comorbidities and a lack of donors. Other treatment options include application of hypomethylating agents or intensive chemotherapy. It has been proven that the treatment with azacitidine delays progression to acute myeloid leukemia, reduces the need for transfusion of red blood cells and causes the increase in overall survival, although does not lead to a cure. The problem with choosing the treatment option occurs in group of the high-risk MDS patients who fail to respond to treatment with azacitidine or who progress during the therapy. It has been shown that this group has acquired cross-resistance to other hypomethylating agents and cytarabine based therapy, but its mechanism is yet to be understood. Because of the fact that the results of MDS treatment using conventional chemotherapy are unsatisfactory, the priority is to create a targeted therapy – monotherapy or combination therapy. The drugs which spark hope for a significant progress in this field are still under a clinical development. They include rigosertib (ON 01910.Na), sapacytabina, clofarabine, farnesyltransferase inhibitors (FTI), inhibitors of histone deacetylase (HDAC), and sorafenib. Let us hope that the use of modern molecular techniques will allow for a more accurate understanding of the pathogenesis of MDS, thus contributing to enhance the impact of its treatment.