Proton-Based Total Marrow Irradiation for Allogeneic Transplantation in High-Risk AML/MDS

Inclusion Criteria: 1. Underlying diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), A) Acute Myeloid Leukemia (AML), meeting at least one of the following criteria: i. Relapsed disease after a prior complete remission (CR) or ii. Disease refractory to at least two cycles of intensive chemotherapy or iii. High-risk AML in complete remission (CR), defined by at least one of the following: iii a) Adverse molecular or cytogenetic risk according to ELN 2022 classification or iii b) Presence of measurable/minimal residual disease (MRD). B) Myelodysplastic Syndrome (MDS), meeting at least one of the following criteria: i. Relapsed MDS with increased blasts (MDS-IB) or ii. MDS-IB2 without reduction of bone marrow blasts below 10% after induction chemotherapy or after at least two cycles of azacitidine or iii. IPSS-M score \> 0.5 (high-risk or very high-risk disease). 2. Eligibility confirmed by the institutionalal Transplant Indication Committee according to standard criteria. 3. Age ≥ 18 years and ≤ 65 years 4. Ability to understand and voluntarily sign written informed consent Exclusion Criteria: Severe comorbidity, defined as the presence of one or more of the following conditions: 1. Left ventricular ejection fraction (LVEF) \< 40% 2. Creatinine clearance \< 0.5 mL/s 3. Total bilirubin \> 40 µmol/L (unless attributable to Gilbert's syndrome or hemolysis) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN) 4. Pulmonary function impairment defined as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) \< 50% of predicted value, or diffusing capacity of the lung for carbon monoxide (DLCO) \< 50% of predicted value after correction for anemia 5. Karnofsky Performance Status \< 70% 6. Active viral hepatitis or human immunodeficiency virus (HIV) infection 7. Presence of liver cirrhosis 8. Pregnancy