Comparison of upfront transplantation and pre-transplant cytoreductive therapy for advanced myelodysplastic syndromes

Abstract Background : Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for advanced myelodysplastic syndromes (MDS). However, the value of pre-transplant cytoreduction remains debatable. Patients and Methods : We retrospectively compared the outcomes of upfront transplantation and pre-transplant cytoreduction. Of 69 patients, 39 received upfront allo-HSCT and 30 received pre-transplant cytoreduction, including chemotherapy (n = 16), hypomethylating agents (HMAs, n = 6), and HMA with chemotherapy (n = 8). Results : The upfront group achieved similar overall survival (OS) and a trend of better progression-free survival (PFS) from diagnosis compared to the cytoreduction group (3-year PFS, 64.0% vs. 44.4%, p = 0.076). Post-transplant outcomes were comparable between the two groups in terms of OS, relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In patients with ≥ 2 mutations, the upfront group achieved better OS and PFS (3-year OS, 100.0% vs. 68.6%, p = 0.044; 3-year PFS: 92.3% vs. 43.9%, p = 0.016) than the cytoreduction group. Patients achieving remission in the cytoreduction group had similar outcomes to the upfront group, but those without remission before transplantation had a significantly worse post-transplant OS (3-year OS, 46.7% vs. 75.7%, p = 0.038). Patients with pre-transplant HMAs had better PFS than those with chemotherapy or HMA plus chemotherapy (p Conclusion : When compared with pre-transplant cytoreduction, upfront allo-HSCT might provide more benefit to some patients with advanced MDS if there are suitable donors. HMAs would be a good alternative during the donor search. Micro-Abstract : The value of pre-transplant cytoreductive therapy for patients with advanced MDS remains controversial. This retrospective study including 69 cases showed patients with upfront transplantation achieved similar outcomes to those receiving pre-transplant cytoreduction. Achieving remission before transplantation led to better survival. This indicates the value of timely transplantation for advanced MDS and suitable pre-transplant therapy during the donor search.