This is an open-label, single-center, non-randomized phase I/II pilot study evaluating proton-based Total Marrow Irradiation (TMI) as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients with high-risk or relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). These patients have an unfavorable prognosis with standard conditioning approaches.
Participants will receive a standard conditioning regimen consisting of either myeloablative or reduced-intensity chemotherapy, selected according to age and comorbidities, combined with proton TMI delivered at a total dose of 12 Gy in three fractions. Graft-versus-host disease (GvHD) prophylaxis will be administered according to institutional standards, preferentially using post-transplant cyclophosphamide. Patients will subsequently undergo standard allo-HSCT and will be followed for at least 24 months after transplantation.
The primary objective of the study is to assess the safety and tolerability of proton TMI added to standard conditioning, as measured by non-relapse mortality and treatment-related toxicity within the first 100 days after transplantation. Secondary objectives include evaluation of engraftment kinetics, incidence of relapse, overall and relapse-free survival, GvHD outcomes, and quality of life. Study outcomes will be analyzed descriptively and compared with a matched historical cohort.
Underlying diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS),
Eligibility confirmed by the institutionalal Transplant Indication Committee according to standard criteria.
Age ≥ 18 years and ≤ 65 years
Ability to understand and voluntarily sign written informed consent
Left ventricular ejection fraction (LVEF) < 40%
Creatinine clearance < 0.5 mL/s
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)
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
Institute of Hematology and Blood Transfusion, Czech Republic
Lead sponsor
Proton Therapy Center Czech s.r.o.
Collaborator