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Child to Adult

Age 6: months to <22 years at enrollment. Diagnosis: - Diagnosed with ALL, AML, or MDS for which an allogeneic hematopoietic stem cell transplant is indicated. - Has not received a prior allogeneic hematopoietic stem cell transplant. - Does not have a suitable HLA-matched sibling donor available for stem cell donation. - Has an eligible haploidentical related family donor based on at least intermediate resolution HLA typing. - Patients who also have an eligible 8/8 MUD adult donor based on confirmatory high resolution HLA typing are eligible for randomization to Arm A or Arm B. -Patients who do not have an eligible MUD donor are eligible for enrollment to Arm C.Patient Eligibility Criteria for Enrollment Age 6 months to <22 years at enrollment. Diagnosis - Diagnosed with ALL, AML, or MDS for which an allogeneic hematopoietic stem cell transplant is indicated. For disease eligibility to proceed to transplant see Sections 4.2.4-4.2.5. Complete Remission (CR) status will not be confirmed at the time of enrollment. CR as defined in these sections is -required to proceed with the actual HCT treatment plan. - Has not received a prior allogeneic hematopoietic stem cell transplant. - Does not have a suitable HLA-matched sibling donor available for stem cell donation. - Has an eligible haploidentical related family donor based on at least intermediate resolution HLA typing. - Patients who also have an eligible 8/8 MUD adult donor based on confirmatory high resolution HLA typing are eligible for randomization to Arm A or Arm B. - Patients who do not have an eligible MUD donor are eligible for enrollment to Arm C. Exclusion Criteria for Enrollment - Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL with known poor outcomes because of sensitivity to alkylator therapy and/or TBI are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc). Patients with Downs syndrome because of increased toxicity with intensive conditioning regimens. - Patients with any obvious contraindication to myeloablative HCT at the time of enrollment - Pregnant and Breastfeeding - Female patients who are pregnant are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants - Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.