Allogeneic stem cell transplantation in myelodysplastic syndromes: does pretransplant clonal burden matter?

PURPOSE OF REVIEW: Currently, the only potential curative therapy for myelodysplastic syndromes (MDS) is allogeneic hematopoietic stem cell transplantation (alloSCT). As alloSCT confers both a short-term mortality risk compared with conservative management, and a longer-term risk of chronic health burden from graft-versus-host disease and other complications, careful patient selection for alloSCT is essential. Here, we review data on disease burden and transplant outcomes in MDS, describing which patients stand to benefit most (and least) from alloSCT. Evidence for timing of alloSCT and modifying tumor burden prior to transplant is also discussed. RECENT FINDINGS: Although patients who undergo alloSCT with excess blasts have poorer outcomes than those transplanted with fewer blasts, the effect of clone size in patients with MDS without increased blast proportion is poorly studied, and it is also not yet known whether posttransplant outcomes can be modified with pretransplant therapy such as intensive induction chemotherapy or hypomethylating agent treatment. Randomized data are lacking. Most hematopoietic cells in patients with MDS are clonal, even in cases without increased marrow blast proportion. Certain high-risk point mutations such as TP53 seem to be associated with a worse outcome even when subclonal. SUMMARY: Patients with more than 10% blasts should be considered for cytoreductive therapy before transplant, especially if reduced intensity conditioning (alloSCT) is planned. Patients with less than 10% blasts who are appropriate candidates for transplant can proceed straight to transplant, though it appears better to delay transplant for those with lower-risk disease. Hypomethylating agent therapy may be useful as a bridge to transplant. Randomized data are eagerly awaited.