Donor Blood Stem Cells (TCR Alpha/Beta and CD19-Depleted Stem Cells) for the Prevention of Graft-versus-Host Disease in Patients with Cancerous and Non-cancerous Blood Diseases

Inclusion Criteria

• Age 31 days to < 30 years
• Have a malignant or non-malignant hematologic disease, defined as disease resulting from abnormal function of a cell of the hematopoietic stem cell lineage, that could benefit from an allogeneic HCT. * Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias/marrow failure, white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities.
• Clinical remission for patients with acute leukemia (myelodysplastic syndrome [MDS]/acute myeloid leukemia [AML] excluded) or lymphoma
• Lack a healthy and willing human leukocyte antigen (HLA)-identical related donor, with the exception of patients with Fanconi anemia (FA) who will be eligible with a willing HLA-identical related donor given the standard use of T-cell depletion in matched sibling donor HCT in FA
• Have a related or an unrelated donor who meets the donor selection criteria, is healthy, willing, and able to receive granulocyte-stimulating factor (GCSF) with or without plerixafor, and undergo apheresis through placement of catheters in the antecubital veins or a temporary central venous catheter
• Able to give informed consent if >= 18 years, or with legal guardian capable of giving informed consent if < 18 years
• Provision of signed and dated informed consent form
• RELATED DONOR: Sibling, half-sibling, parent, cousin, aunt, uncle, or grandparent are all eligible, including both minor and adult donors
• RELATED DONOR: Age >= 7 years of age
• RELATED DONOR: Meet criteria for apheresis as defined by institutional apheresis guidelines
• RELATED DONOR: HLA antigen genotypic match >= 5/10
• RELATED DONOR: Preferred absence of anti-HLA antibodies in recipient directed against donor antigens
• RELATED DONOR: If donor is female and of child-bearing age, negative pregnancy test
• UNRELATED DONOR: 9/10 or 10/10 HLA antigens match
• UNRELATED DONOR: Preferred absence of anti-HLA antibodies in recipient directed against donor antigens
• UNRELATED DONOR: If donor is female and of child-bearing age, negative pregnancy test
• UNRELATED DONOR: Must follow National Marrow Donor Program (NMDP)/Be The Match Algorithm Guidelines for Unrelated Donors
• DONOR SELECTION CRITERIA IN DECREASING ORDER OF PRIORITY:
• Absence of donor-specific HLA antibodies is preferred * If donor-specific anti-HLA antibodies cannot be avoided, the risks of using such a donor will be discussed with the patient and consenting parent/guardian and options including antibody reduction (in the recipient), using an alternative donor or transplant approach or deferring transplant will all be considered
• If more than one donor is available with absent or equivalent donor-specific anti-HLA antibodies, the following prioritization will be used: * ABO-compatible donor is preferable to ABO-incompatible donor * Cytomegalovirus (CMV) status * For a CMV seronegative patient, prefer a CMV seronegative donor * For a CMV seropositive patient, prefer a CMV seropositive donor * For donors > 18 years of age, younger donor is preferable to older, avoiding those > 40 years of age if possible * Male donor preferred over nulliparous female donor over multiparous female donor

Exclusion Criteria

• Uncontrolled, active infection at time of HCT
• Human immunodeficiency virus (HIV) positivity
• Cardiac ejection fraction < 45%
• Creatinine clearance < 60 mL/min/1.72 mL
• Pulmonary diffusion capacity (adjusted for hemoglobin), forced expiratory volume in 1 second (FEV1), or forced vital capacity (FVC) < 60% of predicted or an oxygen (O2) saturation < 94% on room air if unable to perform pulmonary function testing
• Serum alanine aminotransferase (ALT) > 5x upper limit of normal
• Serum bilirubin >2
• Performance score (Lansky or Karnofsky) < 50
• Pregnant or lactating females, as many medications necessary for a successful HCT are potentially harmful to unborn babies and infants.