This trial studies how well radiation therapy techniques, volumetric modulated arc therapy (VMAT) and tomotherapy, work to reduce doses to the lung compared to standard total body irradiation methods to prevent pulmonary toxicities. Standard total body irradiation is limited in its ability to spare normal organs, with only the lung being partially spared by lung blocks and risks the development of pulmonary toxicities. Reducing the doses to the lung using VMAT or tomotherapy may improve survival and decrease long term lung side effects in patients undergoing stem cell transplant.

PRIMARY OBJECTIVES:

I. To test whether the investigators can achieve a mean lung dose of < 8 Gy and still treat the total body at a minimum of 85% prescribed dose in patients undergoing allogeneic hematopoietic stem cell transplantation who are eligible for standard total body irradiation (TBI)-based myeloablative regimens.

II. To evaluate TBI coverage from tomotherapy and VMAT with new lung sparing guidelines.

III. To assess the rate of adverse events with intensity-modulated radiation therapy (IMRT) TBI: type, frequency, severity, attribution, time course, duration, and complications (acute graft versus host disease [GvHD], infections, and delayed neutrophil/platelet engraftment) measured by Bearman and Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

SECONDARY OBJECTIVES:

I. To evaluate dose homogeneity for all target and non-target structures using dose volume histograms.

II. To evaluate non-relapse mortality at 100 days, and 1 year post IMRT TBI. III. To evaluate relapse-free survival (RFS) at 100 days, and 1 year post IMRT TBI.

IV. To evaluate extramedullary recurrence rate at 1 year post IMRT TBI.

OUTLINE:

Patients undergo TBI using IMRT with VMAT or tomotherapy twice daily (BID) on days -7 to -4 then undergo stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 100 days and 1 year post transplant.

Inclusion Criteria:

• Karnofsky performance status (KPS) >= 70
• Acute leukemia or myelodysplastic patients evaluated within 30 days of start of conditioning regimen who would be candidates for TBI-cyclophosphamide (Cy) or TBI-etoposide (VP16) per City of Hope (COH) standard operating procedure (SOP) for allogeneic hematopoietic stem cell transplant
• Patients must be suitable for TBI conditioning regimens as part of transplant per the referring hematologist
• Patients must have adequate organ function for hematopoietic cell transplantation (HCT) as determined by the hematologist
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation
• All subjects must have the ability to understand the treatment and the willingness to sign a written informed consent
• The effects of total body radiation on the developing fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Although not mandated by the protocol, the results of the imaging scans and labs (complete blood count [CBC], comprehensive metabolic panel [CMP]) that are performed as part of the standard work up should be available and should have been done within 2 months prior to study entry
• Prior therapy (chemotherapy, immunotherapy, radiotherapy) must be completed at least 2 weeks prior to TBI
• All patients with prior radiotherapy need to be reviewed with the principal investigator (PI) to determine eligibility
• Prior therapy with chemotherapeutic agents is allowed
• DONOR: Donor evaluation and eligibility will be assessed per current COH standard operating procedure

Exclusion Criteria:

• Patients should not have any uncontrolled illness including ongoing or active infection
• Prior history of radiation therapy must be presented to study PI for eligibility determination
• Pregnant women are excluded from this study because total body irradiation is an agent with the potential for teratogenic or abortifacient effects
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study