AbstractThe myelodysplastic syndrome-myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative clinical, laboratory, and morphological overlapping features, both in marrow and in blood. MDS/MPNs include chronic myelomonocytic leukemia (CMML), MDS/MPN with neutrophilia, MDS/MPN with SF3B1 mutation (in its absence with ringed sideroblasts) and thrombocytosis (MDS/MPN-SF3B1-T), and MDS/MPN not otherwise specified (MDS/MPN-NOS). Prognosis of MDS/MPN is highly variable, being dismal in the majority of patients with CMML, MDS/MPN with neutrophilia and MDS/MPN-NOS. In the absence of disease-modifying treatment options, allo-HCT represents the only curative option for eligible patients. With regard to allo-HCT indication in CMML patient, a number of prognostic systems have been developed over the years. As far as pre-transplant phase, in high-risk patients with MDS/MPN and low blast count (<10%), upfront transplantation is the most frequently preferred strategy. In patients with high blast count, pre-transplant treatment with HMAs, or combination of HMAs with other new agents in clinical trials may be considered. In case of rising leukocytosis and/or organ infiltration, hydroxyurea is the drug of choice. In MDS/MPN patients, the choice of conditioning regimen depends on many different conditions, the major ones being comorbidities, patient age, disease phase at transplant, type of donor, and HSC source. In general, myeloablative regimens may be advisable in young patients without comorbidities aiming to reduce the relapse risk, while reduced-intensity regimens are preferred for patients with older age or comorbidities. As disease recurrence represents the major cause of transplant failure in MDS/MPN, there is a growing interest toward possible post-transplant treatment strategies, both as preemptive and as prophylactic modalities.