Epigenetic approaches in the treatment of myelodysplastic syndromes: clinical utility of azacitidine

Figures & data

Table 1 Treatment approach in nontransplant candidates at the University of Minnesota

INT-1/low-risk IPSS

No treatment indicated → supportive measures only Symptomatic anemia If anemic + low EPO level: trial of EPO supplementation with or without G-CSF Transfusion-dependent anemia not responding to growth factors 5q–: lenalidomide Normal/other cytogenetics: order of treatment choice Azacitidine Clinical trial ATG/CSA: if younger (<60 years) or HLA DR15 Neutropenic or thrombocytopenic requiring therapy Azacitidine Clinical trial if not responding to azacitidine

INT-2/high-risk IPSS

Requiring therapy Azacitidine Clinical trial if progression on azacitidine

Abbreviations: EPO, erythropoietin; G-CSF, granulocyte-colony-stimulating factor; ATG, antithymocyte globulin; CSA, cyclosporine; HLA-DR15, human leukocyte antigen DR-15.

Table 2 Treatment approach in transplant candidates at the University of Minnesota

Low-risk IPSS	Supportive care as above
	Due to potential long natural history, transplant typically not indicated up front, even in young patients, unless showing evidence of progression
	Note: Patients with transfusion dependency not responding to therapy (growth factors, hypomethylating agents, etc) should be transplanted earlier despite their low-risk IPSS score due to higher TRM noted with higher pretransplant ferritin levels and transfusion dependence
INT-1 IPSS	Age ≥50 years: Poorer outcomes compared with younger patients. Thus, consideration of transplantation at diagnosis
	If <5% blasts in marrow at diagnosis: Transplant with no up front therapy
	If >5% blasts in marrow at diagnosis: Initiate therapy to reduce blast percentage and proceed to transplant
	Therapy choice
	Azacitidine: 1st choice if have time to achieve benefit
	AML type induction chemotherapy: If high proliferative capacity and need urgent response
	If age <50 years: May have prolonged natural history without significant intervention, so no transplant up front unless failure of below interventions or progressive cytopenias/disease progression
	Supportive care if minimal cytopenias
	Thrombocytopenic/neutropenic requiring treatment:
	Azacitidine
	Symptomatic anemia requiring transfusions
	5q–: patients: Lenalidomide
	Normal/other cytogenetics: Azacitidine
	If progressed through above therapies and need further disease reduction prior to transplantation → clinical trial
INT-2/high-risk	All age patients (<70–75 years)
IPSS/t-MDS	Prepare for allogeneic HCT from diagnosis: HLA type patient, sibs, initiate MUD/cord search if no sibling match
	Treatment, as needed, to reach goal of <5% blasts
	Azacitidine 1st choice: (needs 3 to 4 cycles to assess true response)
	Induction chemotherapy if high proliferative rate
	Clinical trial if suboptimal response to above and need further disease reduction pretransplant

Abbreviations: TRM, treatment-related mortality; AML, acute myeloid leukemia; t-MDS, treatment-related MDS; HCT, hematopoietic stem cell transplant; HLA, human leukocyte antigen; MUD, matched unrelated donor.