L’allogreffe de cellules souches hématopoïétiques reste la meilleure option thérapeutique, potentiellement curative, à proposer aux patients porteurs d’un syndrome myélodysplasique (SMD) de haut risque. Dans cette situation, l’hématologue est amené à discuter l’indication d’un traitement cytoréducteur pré-greffe dans l’espoir de diminuer le risque de rechute après la procédure. L’intérêt d’opter pour cette stratégie thérapeutique est actuellement débattu. Par rapport aux agents hypométhylants (AHM), la chimiothérapie intensive (CI) permet plus fréquemment l’obtention d’une rémission complète, avec des résultats cependant médiocres chez les patients porteurs d’anomalies cytogénétiques défavorables. Les AHM, bien que mieux tolérés que la CI, exposent également le patient à un risque important de toxicité pouvant compromettre la réalisation de l’allogreffe. L’allogreffe d’emblée peut également être une option envisageable et nous proposerons un algorithme décisionnel simple afin d’optimiser la stratégie pré-greffe.

Treatment of myelodysplastic syndromes (MDS) remains unsatisfactory. Variable success in the correction of blood cytopenias, reduction of the proportion of marrow myeloblasts, and normalization of cytogenetics has been achieved with a variety of treatment strategies, including the use of immunosuppressive drugs, differentiating agents, conventional chemotherapy, and hypomethylating agents (HMAs) However, in general, responses have not been complete and have been of limited duration; prolongation of survival, if achieved, on average has been in the range of months. Currently, allogeneic hematopoietic stem-cell transplantation (allo-SCT) remains the only approach with curative potential for patients with higher risk/advanced MDS. Yet, despite the beneficial effects of allo-SCT, post-transplant relapse is a major cause of failure. Debulking prior to transplant treatment in patients with MDS is a matter of debate. The achievement of complete remission (CR) before allo-SCT improves post-transplantation outcome, although it is not clear whether this reflects the selection of patients with more responsive disease or is related to a reduction in disease burden. Higher CR rates in patients with MDS are obtained with induction chemotherapy (ICT) than with hypomethylating agents (HMAs), although HMAs may be active in patients with complex karyotypes in whom ICT almost invariably fails. Furthermore, HMAs have a good toxicity profile compared with ICT and may therefore be considered especially in older patients and in patients with comorbidities. However, all interventions aimed at reducing disease burden before allo-SCT expose patients to the risk of complications, which may prevent them from undergoing transplantation. Therefore, up-front allo-SCT is an option, particularly for patients with life-threatening cytopenias. In the absence of prospective randomized trials, the main therapeutic approaches are discussed in this review.