Table 3.

Individualised therapy decision in elderly patients (≥70 years) with high-risk myelodysplastic syndromes (IPSS Int-2 and High)

Category	Therapy recommendation	Therapeutic target
Go-go/fit	Best supportive carea	Haematologic improvement
	Allo-HSCTb	Curation, prolonged OS and PFS
	Azanucleosidesc	Prolonged OS and PFS, haematologic improvement, relief of symptoms, improved QOL
	Investigational agentsd,e	Therapeutic target according to aim of the investigational study
Slow-go/vulnerable	Best supportive carea	Haematologic improvement
	Azanucleosidesd	Prolonged OS and PFS, haematologic improvement, relief of symptoms, improved QOL, curation
	Investigational agentsd,e	Therapeutic target according to aim of the investigational study
No-go/frail	Best supportive carea	Haematologic improvement, QOL
	(Azanucleosides)f	Improved QOL, haematologic improvement, relief of symptoms
	Investigational agentsd,e	Therapeutic target according to aim of the investigational study

Allo-HSCT allogeneic haematologic stem cell transplantation, OS overall survival, PFS progression-free survival, QOL quality of life

^aSupportive care represents the basis of all therapeutic options in the distinct treatment arms. Median survival in patients >70 years treated with BSC is 14.4 months in IPSS Int-2 and 4.8 months in IPSS high [24]

^bMight be feasible in a minority of selected cases with an excellent health status. In these patients an OS at 2-year of >40 % can be achieved in persons aged 65+ [33]. On the relevance of induction chemotherapy prior to HSCT, there is no consensus yet. Hence, decision should be made on an individual basis, possibly after pretreatment with azanucleosides [30, 31]

^cAzanucleosides such as 5-azacytidine (AZA) (Vidaza®) and 5-azadeoxycytidine/decitabine (DAC) (Dacogen®) are demethylating agents. They have been applied in clinical studies on MDS patients. Vidaza® is approved in this indication in Europe [37], Dacogen® in the USA [39]. The median survival in AZA/BSC only/low-dose Ara-C in the AZA-001 study was 24.5/11.5/15.3 months, respectively [41]; in a subgroup analysis of elderly patients (≥75 years), median OS was not reached at >17 months [41]. Median OS in the French patient-named program was 12.7 months in >70-year-old patients [44]. A prognostic score for patients receiving AZA was developed by Itzykson et al. [44]: three risk groups with OS >24, 15 and 6.1 months, respectively, were defined. Median survival for decitabine-treated patients in the phase-III study by Lübbert et al. [47] was 10.1 months

^dThe inclusion in clinical studies is recommended

^eInvestigational agents include an oral formulation of azacitidine, histone deacetylase inhibitors, lenalidomide and combinations thereof

^fEven a minor portion of no-go patients might benefit from azacitidine