This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.
Histiocytic disorders including hemophagocytic lymphohistiocytosis (familial HLH (types 1-5), secondary HLH (refractory to therapy or with recurrent episodes of hyper inflammation) and multisystem refractory Langerhans cell histiocytosis.
Metabolic disorders that could improve or stabilize after stem cell transplantation such as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.
Patient has a suitable genotypic identical match of 5/10. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.
Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%
Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
Pregnant or breastfeeding females.
Patient has HIV or uncontrolled fungal, bacterial or viral infections.
Patient has received prior solid organ transplant.
Single group
Haploidentical Hematopoietic Cell Transplantation
Biological/VaccineTCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation
Incidence of successful donor engraftment
The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (\< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), \> 95%=full donor chimerism.
Overall survival and Event-free survival
Overall survival is defined as the time of enrollment to death from any cause or last follow up. Event-free survival is defined as the time of enrollment to death, primary or secondary graft failure, graft failure necessitating a second HCT procedure, DLI or stem cell boost given for treatment of falling chimerism, or disease recurrence
Kinetics of neutrophil engraftment
Neutrophil engraftment defined as absolute neutrophil count ≥500/μL for 3 consecutive measurements on different days
Kinetics of platelet engraftment
Platelet engraftment defined as sustained platelet count \>20,000/μL and \>50,000//μL with no platelet transfusions in the preceding seven days.
Transplant-related mortality
Rate of transplant-related mortality
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