Applicable to all Subjects - Signed, informed consent - Participants of childbearing potential must have a negative pregnancy test as per institutional SOP - Patients who do not meet criteria for current open, institutional protocols using CliniMACs device for β T/CD19+ depletion - Patients with the following transplantable diseases: - Non-malignant diseases - Metabolic storage diseases correctable by HSCT - Bone marrow failure syndromes - Immunodeficiencies/immune dysregulation syndromes - Sickle cell disease or thalassemia - Other diseases treated with HSCT o Malignant diseases - Acute leukemias - Chronic leukemias - Lymphomas - Myelodyplastic syndrome Inclusion Criteria: Primary transplant or non-emergent subsequent transplant The conditioning prescribed to the patient will be determined based on the disease and organ status and will include agents that are standard. Appropriate combinations of chemotherapy, immunotherapy and/or radiation will be determined on an individual basis. Patient eligibility will be assessed as per our current institutional standard operating procedures. Patients that meet the following criteria may be eligible: - Lansky or Karnofsky performance ≥ 60 - Hematologic and Organ Function as per current institutional SOP - Infectious Evaluation as per current institutional SOP Inclusion Criteria: Urgent subsequent transplant, with conditioning, in the setting of graft failure or severe marrow dysfunction For subjects undergoing an urgent subsequent transplant, conditioning will be individualized based on the underlying disease, prior transplant history, and current organ function. Subjects with the following may be eligible: - Adequate organ function as determined by the transplant physician to safely tolerate the planned conditioning regimen - No active, uncontrolled infection - Patients whose initial transplant was performed under this protocol, under another clinical protocol, or using a bone marrow graft - Previously collected TCRαβ/CD19 depleted stem cells from this or another approved protocol may be used if available. Inclusion Criteria: Unconditioned Stem Cell Boost/Transplant These subjects will not be required to meet the performance status, hematologic and organ function, or infectious evaluation criteria listed above, as conditioning will not be administered. - Patients with cytopenias due to bone marrow dysfunction, declining donor chimerism, or other treatment needs as determined by the subject's clinical course - Patients with active infections are eligible, as the stem cell boost will be administered without conditioning - Previously collected TCRαβ/CD19 depleted stem cells from this or another approved protocol may be used if available. - Patients who received their initial transplant either on this protocol or on a separate protocol

Applicable to all Subjects - Suitable and available HLA matched sibling donor. However, patients with fully matched related donors (including siblings) may be eligible in special circumstances where use of an unmanipulated bone marrow graft has increased risks for donor or recipient. - Donor unable to donate peripheral stem cells - Pregnant participants Donor Eligibility Patients must have an identified living donor - Donor selection will comply with 21 CFR 1271* - Unrelated donor that meets the matching criteria of the NMDP with allele matching at HLA -A, -B, -C, -DRB1, and -DQB1: Unrelated donors may be a 10/10 match, a 9/10 match, or an 8/10 match if one of the mismatches is at DQB1. - Related donor mismatched at one to five HLA alleles (haploidentical) - Matched related donor may be considered suitable donors for this protocol if a peripheral stem cell donation is deemed by the clinical team to be a safer donation option (if donor is not a suitable candidate for a bone marrow harvest) or if there is concern that bone marrow harvest would not yield adequate cell doses Additionally, a matched related donor would be considered suitable for this protocol if there are safety concerns regarding a patient receiving a standard T cell replete bone marrow transplant due to individualized GVHD risk or risk related to standard GVHD prevention medications. - Donor suitable for mobilization of peripheral stem cells and apheresis and fulfills infectious disease criteria as per our institutional SOP, including HIV, HepB, HepC PCR negative. - We assess donor eligibility as per our Allogenic Donor Evaluation for Eligibility standard operating procedure. These procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. Our donor collection program is FACT accredited. - Related donors will be consented and enrolled under IRB approved research protocol for cell collection per IRB 04-004078 CHP 784 Clinical and Research Collection and Future Research Use of Bone Marrow, Stem Cells or T Cells. - Unrelated donor identified through the National Marrow Donor Program (NMDP) and fulfills the NMDP criteria for donation. Unrelated donor willing and able to undergo mobilization of peripheral stem cells and apheresis. - The donors selected for this IDE will either be unrelated donors identified through the National Marrow Donor Program (NMDP) or related donors. Regarding the unrelated donors, NMDP procedures for determining donor eligibility include donor screening and testing for relevant communicable disease agents and diseases