The goal of this clinical trial is to learn if drugs (fludarabine and melphalan) combinated with a targeted irradiation (in bone marrow and in lymphoid tissue) works to treat blood cancers (high risk myelodysplastic syndrome or acute myeloid leukemia) in adults. It will also learn about the safety of this combination of drugs and irradiation. The main questions it aims to answer are:
* Does this combined therapy result in an improved survival and decreased relapse/progression rate after a bone marrow transplant? * What toxicities or complications do participants have when taking this combined therapy?
Researchers will use this combined therapy to see if it works to treat high risk myelodysplastic syndrome or acute myeloid leukemia through the evaluation of the length of time (during the treatment and 2 years after the treatment) that a patient lives with the disease but it does not get worse (progression-free survival).
Participants will:
* Receive the combined therapy (study treatment) one week before the bone marrow transplant. * Receive too post-transplant medication as per usual clinical practice.
Patients will have to attend medical visits (checkups and tests) for 2 years.
The participant has the ability and willingness to sign the informed consent document. (For adults, only participants with mild cognitive abilities may use a legally authorized representative).
Documented (signed) informed consent. The patient, family member, and doctor of the transplant staff (doctor, nurse, and social worker) meet at least once before the transplant procedure begins. During this meeting, all relevant information regarding the risks and benefits to the donor and recipient will be presented. Alternative treatment modalities will be discussed. The risks are explained in detail in the attached consent forms.
Age: ≥ 50 years or Haematopoietic Cell Transplantation-Comorbidity Index pre-transplant score ≥ 3 or any other condition that precludes the use of a fully myeloablative conditioning regimen.
Karnofsky's performance status ≥ 70%.
Patients who have received a previous autologous (within the last year) or allogeneic transplant (at any time) are excluded.
Previous radiation therapy which would preclude the use of TMLI.
Plans during the trial to receive any other investigational (non-trial-related) agents.
Uncontrolled disease, including ongoing or active infection.