TMLI Plus Chemotherapy in High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

Inclusion Criteria:

* The participant has the ability and willingness to sign the informed consent document
* Age ≥18 to ≤50 years.
* Karnofsky's performance status should be ≥70%.
* Patients with myelodysplastic syndrome/acute myeloid leukemia or acute myeloid leukemia with relapsed/refractory active disease, or in complete remission or morphologic leukemia-free state with evidence of measurable residual disease as assessed by multiparameter flow cytometry (≥ 0,1%) or next-generation sequencing
* All candidates for this study must have an Human leukocyte antigens (A, B, C, DR) identical siblings who are willing to donate bone marrow or peripheral blood hematopoietic progenitors or an 8/8 matched unrelated donor. A single allele mismatch in A, B, C or DR beta chain 1 shall be allowed
* Total bilirubin ≤ 1.5 x upper limit of normal or 3 x upper limit of normal for Gilbert's disease.
* serum glutamate oxaloacetate transaminase \& serum glutamate pyruvate transaminaseT ≤ 5 x upper limit of normal.
* Serum creatinine ≤ 1.3 mg/dL or creatinine clearance measured ≥ 80 mL/min for 24 hours of urine collection
* Women of childbearing age only: Negative urine or serum pregnancy test
* Pulmonary function tests: forced expiratory volume in one second and Carbon Monoxide Diffusion Capacity (adjusted for Hb) ≥ 50% from expected normal value
* Patients should undergo cardiac evaluation with an electrocardiogram showing no ischemic changes or clinically relevant arrhythmia, and a ≥50% ejection fraction established by Multi-Gated Acquisition Scan or echocardiogram
* Men and women of childbearing potential agree to use appropriate contraceptives (hormonal or barrier contraception or abstinence) prior to study entry and for six months following the duration of study participation
* The time elapsed since the end of the last induction or reinduction cycle must be greater than or equal to 14 days

Exclusion Criteria:

* 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 total bone marrow and lymphoid irradiation
* Plans during the trial to receive any other investigational (non-trial-related) agents
* Uncontrolled disease, including ongoing or active infection
* History of allergic reactions attributed to compounds of chemical or biological composition similar to cyclophosphamide or etoposide
* Patients with other active malignancies are not eligible for this study, other than the malignancies discussed
* Patients with a psychological or medical condition that the patient's physician deems unacceptable to proceed with allogeneic hematopoietic stem cell transplantation
* Women who plan to become pregnant or breastfeed during the trial
* Patients who do not agree to practice effective forms of contraception
* Subjects who, in the opinion of the investigator, may not be able to meet the safety control requirements of the study