Donor Stem Cell Transplant after TCR Alpha-Beta+ T Cells/CD19+ B Cell Depletion for the Treatment of Children and Young Adults with Malignant or Non-malignant Hematological Disorders

Inclusion Criteria

• Age < 60 years and > 1 month
• Life expectancy > 10 weeks
• Patients deemed eligible for allogeneic HSCT per institutional guidelines
• Patients with life-threatening hematological malignancies and non-malignant disorders that could benefit from HSCT; a minimum genotypic identical match of 5/10 is required
• The donor and recipient must be identical, as determined by high resolution typing, in at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB1
• Lansky/Karnofsky score > 50; the Karnofsky scale will be used in subjects >= 16 years of age, and the Lansky Scale will be used for those < 16 years of age
• All subjects >= 18 years of age must be able to give informed consent. For subjects < 18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate
• Male and female subjects of childbearing potential must agree to use an effective means of birth control to avoid pregnancy throughout the transplant procedure, while on immunosuppression, and if the subject experiences any chronic GvHD
• DONOR INCLUSION
• Age < 65 years for adult donors; for pediatric donors, weight greater than 10 kg
• Sufficiently healthy not to be at increased risk from the mobilization procedure
• Must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened as applicable per the Food and Drug Administration (FDA) and American Association of Blood Banks (AABB) guidelines
• Donor must have adequate peripheral venous access for leukapheresis or must agree to placement of a central venous catheter
• Signed informed consent
• Should more than one “equally” major histocompatibility (MHC) compatible donor be identified, other selection criteria may include natural killer cell (NK) alloreactivity, NK cell killer cell immunoglobulin-like receptor (KIR)-haplotype, B-content for B-haplotype donors, size of the NK alloreactive subset, gender, age, cytomegalovirus (CMV) status, health status and body weight of donor. The physician treating the subject will make the final decision
• In case of positive cross-match results for donor-reactive anti HLA antibodies an alternative donor with negative cross-match results is preferred, if available. If no alternative donor with negative cross-match results is available, removal of anti-human leukocyte antigen (HLA) antibodies is highly recommended to prevent graft rejection

Exclusion Criteria

• Pregnant or lactating females
• Greater than grade II acute GvHD or severe, unmanaged chronic extensive GvHD due to a previous allograft at the time of inclusion
• Dysfunction of liver (alanine aminotransferase [ALT]/aspartate aminotransferase [AST] > 10 times upper normal value, or direct bilirubin > 3 times upper normal value), or unmanageable dysfunction of renal function
• Severe cardiovascular disease (congestive heart failure or left ventricular ejection fraction < 30%)
• Current active infectious disease (including positive human immunodeficiency virus [HIV] serology or viral ribonucleic acid [RNA])
• Serious concurrent uncontrolled medical disorders
• Lack of patient’s/parents’/guardian’s informed consent
• Any severe concurrent disease which, in the judgement of the sponsor-investigator, would place the patient at increased risk during participation in the study
• DONOR EXCLUSION
• Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) or viral hepatitis exposure (on screening), unless hepatitis B surface antibody positive (HBs Ab+) and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) negative
• Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy (e.g., autoimmune disease, sickle cell trait, symptomatic coronary artery disease requiring therapy, previous thrombotic events)
• Pregnancy (positive serum or urine beta-human chorionic gonadotropin [HCG]) at the time of G-CSF mobilization
• Breastfeeding at the time of G-CSF mobilization. Note: consider suspending breastfeeding during the G-CSF mobilization in situation where most suitable donor is breast feeding