Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Inclusion Criteria:

Patients with a diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) with fewer than 10% myeloblasts or lymphoblasts in the bone marrow and no blasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen; if remission bone marrow is available beyond 30 days a new bone marrow evaluation is required to assess remission status

The diagnosis of AML, ALL, or MDS will be based on World Health Organization (WHO) criteria
Pre-transplant bone marrow sample must be evaluable for assessment of remission status (i.e. aspirate smear containing particles and/or evaluable bone marrow core biopsy)
Patients with leukemia infiltration in the central nervous system (CNS) are eligible if cerebrospinal fluid (CSF) cytospin is negative for myeloblasts or lymphoblasts at time of enrollment
If the patient has an intra-abdominal chloroma on presentation, and has a partial response or complete response to treatment (size reduction of chloroma and marrow blast < 10%), the patient is eligible; however the chloroma must be included as part of the treatment target

For patients receiving treatment of their AML, MDS or ALL prior to transplantation:

Interval between the start of a cycle of conventional cytotoxic chemotherapy and the start of conditioning regimen must be at least 30 days
Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and the start of conditioning regimen must be at least 10 days
Hematopoietic Cell Transplantation-Specific Comorbidity Index score (HCT-CI) =< 4 for patients in Cohort 1 and > 4 for Cohort 2
Patient must be able to lie still in full body cast for 45 minutes
Must have a suitable donor defined as a sibling matched at 5/6 or 6/6 antigens (human leukocyte antigen [HLA]-A, B, and DRB1) or an unrelated volunteer matched at 7/8 or 8/8 HLA alleles (HLA-A, B, C, and DRB1)
Signed informed consent

DONOR: "High resolution" typing at HLA-A, B, C and DRB1 alleles

Single antigen mismatch for siblings and single allele mismatch for volunteer unrelated donors is acceptable
Donors must be >= 17 years of age

Exclusion Criteria:

Circulating peripheral blood myeloblasts or lymphoblasts on morphologic analysis from time of last treatment to time of enrollment
Prior allograft or prior autograft
Active CNS disease as identified by positive CSF cytospin at time of enrollment
Karnofsky performance score < 70
Symptomatic uncontrolled coronary artery disease or ejection fraction < 40%
Total bilirubin >= 2 x the upper limit of normal
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x the upper limit of normal
Diffusion capacity of the lung for carbon monoxide (DLCO) < 40%
Forced expiratory volume in one second (FEV1) < 50% (corrected for hemoglobin)
Receiving supplementary continuous oxygen
Creatinine clearance < 50 mL/min/1.73m^2
Patients with active uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms)
Patients seropositive for the human immunodeficiency virus (HIV)
Females who are pregnant or breastfeeding
Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
Patients who had prior radiation to more than 20% bone marrow containing areas or to any areas exceeding 2000 cGy

DONOR:

Donors will be excluded if they are an identical twin of the recipient
Females who are pregnant (positive serum beta human chorionic gonadotropin beta [β HCG]) or uninterruptible breastfeeding
HIV seropositive
Donors receiving experimental therapy or investigational agents unless approved by the protocol chair