Preparation for bone marrow transplant through the combined use of chemo and radiotherapy (intensive or myeloablative: eliminates stem cells)

Prior treatment

• 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

Other illness

• 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

Other

• Subjects who, in the opinion of the investigator, may not be able to meet the safety control requirements of the study
• Plans during the trial to receive any other investigational (non-trial-related) agents
• Women who plan to become pregnant or breastfeed during the trial
• Patients who do not agree to practice effective forms of contraception

• The participant has the ability and willingness to sign the informed consent document
• Pulmonary function tests: forced expiratory volume in one second (FEV1) and Carbon Monoxide Diffusion Capacity (DLCO) (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 Acquisiton Scan (MUGA) or echocardiogram
  • ECG showing no ischemic changes or clinically significant arrhythmia
  • 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
  • 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 (in the case of FLT3-ITD-mutated AML)
  • All candidates for this study must have an HLA (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 DRB1 shall be allowed
  • Total bilirubin ≤ 1.5 x ULN OR 3 x ULN for Gilbert's disease
  • SGOT & SGPT ≤ 5 x LSN
  • 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