Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute Leukemia

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• Karnofsky performance status >= 70

• Histologically confirmed diagnosis of one the following:

• Patients with acute myelogenous leukemia

• In first complete remission (CR1) with intermediate or poor riskcytogenetics according to National Comprehensive Cancer Network (NCCN)guidelines for acute myeloid leukemia (AML) or European LeukemiaNet (ELN) 2017

• In second complete remission (CR2) or third complete remission (CR3)

• Patients with chemosensitive active disease

• Patients with acute lymphocytic leukemia

• In CR1 with poor risk cytogenetics:

• For adults according to NCCN guidelines for acute lymphoblastic leukemia (ALL):Patients older than 40 year of age; with high white blood cell count (WBC) atdiagnosis (>= 30,000 for B lineage or >= 50,000 for T lineage), or with highrisk cytogenetics including: hypoploidy (< 44 chromosomes); t(v;11q23): MLLrearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomalabnormalities)

• For pediatrics t(9;22), iAMP21loss of 13q, and abnormal 17p

• In CR2 or CR3

• Patients with chemosensitive active disease

• Myelodysplastic syndrome in high-intermediate (int-2) and high risk categoriesby International Prognostic Scoring System (IPSS) or revised (R)-IPSS

• Total bilirubin =< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwisestated)

• Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gaultformula (to be performed within 28 days prior to day 1 of protocol therapy unlessotherwise stated)

• Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) >= 50% (to be performed within 28 days prior to day 1 of protocol therapy unlessotherwise stated)

• Note: To be performed within 28 days prior to day 1 of protocol therapy

• If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capability test (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin). Ifunable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air

• Note: To be performed within 28 days prior to day 1 of protocol therapy

• Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab)combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigennegative), and syphilis (rapid plasma reagin [RPR]) (to be performed within 28 daysprior to day 1 of protocol therapy unless otherwise stated)

• If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed

• Meets other institutional and federal requirements for infectious disease titerrequirements

• Note: Infectious disease testing to be performed within 28 days prior to Day 1of protocol therapy

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

• If the urine test is positive or cannot be confirmed as negative, a serumpregnancy test will be required

• Agreement by females and males of childbearing potential* to use an effective methodof birth control or abstain from heterosexual activity for the course of the studythrough at least 6 months after the last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

• The recipient must have a related donor genotypically human leukocyte antigen (HLA)-A, B,C and DRB1 loci haploidentical to the recipient

• No HLA matched sibling or matched unrelated donor is available

• Patients should be off all previous intensive therapy, chemotherapy or radiotherapyfor 3 weeks prior to commencing therapy on this study

• (NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days ofplanned study enrollment is permitted. These include: Hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosinekinase inhibitors [TKIs]. FLT-3 inhibitors such as sorafenib, crenolanib,midostaurin can also be given up to 3 days before conditioning regimen.)

• DONOR: The donor must be examined and have specific tests performed according toexisting institutional guidelines to evaluate his/her candidacy as a donor includingthe following:

• DONOR: Age =< 60 years of age

• DONOR: For younger donors, no more than 20 mL bone marrow may be harvested per kg ofdonor body weight

• DONOR: Medical history and physical examination confirm good health status asdefined by institutional standards

• DONOR: Seronegative for HIV Ag, HIV 1+2 Ab, HTLV I/II Ab, hepatitis B surfaceantigen (HBsAg), hepatitis B core antibody (HBcAb) (IgM and IgG), HCV Ab, RPR forsyphilis within 30 days of apheresis collection

• DONOR: Genotypically haploidentical as determined by HLA typing, preferably anonmaternal HLA haploidentical relative due to data of high incidence of graftfailure with use of maternal HLA haploidentical cells. Eligible donors includebiological parents, siblings or half siblings, or children

• DONOR: Female donors of child-bearing potential must have a negative serum or urinebeta-human chorionic gonadotropin (HCG) test within seven days of mobilization

• DONOR: The donor must have been informed of the investigational nature of this studyand have signed a consent form in accordance with Federal Guidelines and theguidelines of the participating institution

• DONOR: Selection of a haploidentical donor will require absence of pre-existingdonor-directed anti-HLA antibodies in the recipient

Exclusion Criteria:

• Patients should not have any uncontrolled illness including ongoing or activebacterial, viral or fungal infection

• Patient may not be receiving any other investigational agents or concurrentbiological, intensive chemotherapy or radiation therapy for the previous three weeksfrom conditioning

• (NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days ofplanned study enrollment is permitted. These include: Hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosinekinase inhibitors [TKIs]. FLT-3 inhibitors such as sorafenib, crenolanib,midostaurin can also be given up to 3 days before conditioning regimen.)

• Herbal medications dependency

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to study agent

• No intercurrent illness or other malignancy (other than non-melanoma skin cancer)

• Active infection requiring antibiotics

• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis Cinfection

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

• Patients who had a prior autologous or allogeneic transplant

• Patients who had prior radiation therapy of more than 20% of bone marrow containingareas or to any area exceeding 2000 cGy

• Patients with HLA-matched or partially matched (7/8 or 8/8) related or fully matchedunrelated donor available to donate

• Patients who have received more than 3 prior regimens, where the regimen intent wasto induce remission

• Patients with treatment history including anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg)

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)

• DONOR: Evidence of active infection

• DONOR: Medical or physical reason which makes the donor unlikely to tolerate orcooperate with growth factor therapy and leukapheresis

• DONOR: Factors which place the donor at increased risk for complications fromleukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy

• DONOR: HIV positive