Automated Total Marrow and Lymphoid Irradiation for Allogeneic Hematopoietic Cell Transplant

Prior treatment

• Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
• GVHD requiring systemic therapy including \> 0.25 mg/kg prednisone (or equivalent) or other systemic therapy for GVHD (e.g., tacrolimus, sirolimus, ruxolitinib, belumosodil, ibrutinib, axatilimab).
• Exposure to prior radiation that is deemed unsafe for clinical trial participation.

Other illness

• Untreated active infection. Controlled or asymptomatic infections requiring continued antimicrobial therapy are permissible.
• Active HIV infection, defined as HIV infection with detectable viral load
• Active central nervous system malignancy
• Any other medical or psychological condition that is deemed serious and unsafe for clinical trial participation.

• Age, Performance Status, and Graft Criteria require all of the following bullet points:
  • Age 18 to 60 years (inclusive)
  • HCT Co-Morbidity score (HCT-CI) \< 5 (http://www.qxmd.com/calculate-online/hematology/hct-ci)(31)
  • Adequate performance status is defined as Karnofsky score ≥ 70%
  • Patients must be receiving an allogeneic peripheral blood stem cell graft
  • Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8/8 matched sibling donor, 8/8 matched unrelated donor, haploidentical related donor, or 7/8 mismatched unrelated donor.
• Eligible Diseases (Any one of the following)
  • Acute Myeloid Leukemia (AML) Must have at least one of the following characteristics:
  • Blasts \>5% in the peripheral blood and/or bone marrow after \>2 prior lines of AML directed therapy, present during the trial screening window
  • Adverse plus risk by AlloHCT Refined ELN Criteria: defined as having complex cytogenetics, TP53 mutation, or MECOM rearrangement confirmed at any time point.(32)
  • Myelodysplastic syndrome Must have at least one of the following characteristics at the time of conditioning:
  • Blasts \>10% in the peripheral blood and/or bone marrow after \>1 prior line of therapy.
  • TP53 mutation confirmed at any time point
  • Myeloproliferative neoplasms (MPN) or MDS/MPN overlap. Must have at least one of the following characteristics:
  • Blasts \>10% in the peripheral blood and/or bone marrow during the trial screening window
  • TP53 mutation confirmed at any time point
• Adequate organ function is defined as all of the following:
  • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction \> 45% confirmed by MUGA or echocardiography Pulmonary: DLCO, FEV1, FVC \> 50% predicted, and absence of O2 requirements. Liver: Transaminases \< 3 x upper limit of normal (ULN) and total bilirubin ≤ 2 mg/dL except for patients with Gilbert's syndrome or hemolysis (as indicated by provider documentation).
  • Renal: Creatinine \< 2.0 mg/dL (adults) and creatinine clearance \> 40 mL/min.
• Must be FIRST allogeneic HCT
• Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
• Voluntary written consent
• Age, Performance Status, and Graft Criteria require all of the following bullet points:
  • Age 18 to 70 years (inclusive) Adequate performance status is defined as Karnofsky score ≥ 70% Patients must be receiving an allogeneic peripheral blood stem cell graft Patients and selected donor must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1. Donors may be an 8/8 matched sibling donor, 8/8 matched unrelated donor, haploidentical related donor, or 7/8 mismatched unrelated donor.
• Eligible Diseases (Any of the following) Acute Myeloid Leukemia (AML) Myelodysplastic syndrome Myeloproliferative neoplasm MDS/MPN overlap
• Must have relapse after prior allo HCT
• Adequate organ function is defined as all of the following:
  • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction \> 40% confirmed by MUGA or echocardiography Pulmonary: DLCO, FEV1, FVC \> 40% predicted, and absence of O2 requirements. Liver: Transaminases \< 3 x upper limit of normal (ULN) and total bilirubin ≤ 2 mg/dL except for patients with Gilbert's syndrome or hemolysis (as indicated by provider documentation).
  • Renal: Creatinine \< 2.0 mg/dL (adults) and creatinine clearance \> 40 mL/min. Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
• Voluntary written consent