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

Inclusion Criteria

• The diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) will be based on World Health Organization (WHO) criteria
• Patients with a diagnosis of AML, ALL, or 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 * 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) of 2-4 for patients in cohort 1, =< 3 for patients in cohort 2 and =< 2 for patients in cohort 3
• 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 >= 18 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
• Patients with prolonged neutropenia (> 2 weeks at time of screening) should be evaluated on a case-by-case basis with regards to risk of infection and should be discussed at bone marrow transplantation (BMT) census meeting prior to enrollment
• 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 [B HCG]) or uninterruptible breastfeeding * HIV seropositive * Donors receiving experimental therapy or investigational agents unless approved by the protocol chair