This study is being done to see if the investigators can take peripheral blood stem cells from either an adult family member or a closely matched unrelated donor, and run them through a special lab instrument to remove alpha/beta T cells and B cells and then give them to the patient to treat disease. This is an experimental way of doing a hematopoietic stem cell transplant (HSCT). The investigators want to see if the new stem cells will grow without bad graft vs. host disease (GVHD). This treatment approach is experimental in the United States.
No Human leukocyte antigen (HLA) identical sibling available AND
NO HLA matched unrelated donor available OR urgent need of HSCT precludes time necessary to search for suitable HLA matched unrelated donor AND
Haploidentical donor OR closely matched unrelated donor available and willing to undergo mobilization and apheresis
If subject has genetically confirmed inherited bone marrow failure, related donor must be evaluated for this disorder and testing must be negative.
Pregnant
HIV infection
Uncontrolled, serious active infection at screening
Significant serious intercurrent illnesses
Single group
TCRαβ+/CD19+ depleted Hematopoietic stem cell (HSC) graft
Biological/VaccineAfter undergoing a disease specific conditioning regimen (standard of care), participants will receive peripheral blood stem cell transplant from a haploidentical donor or closely matched unrelated donor, depleted of TCR αβ+ and CD19+ cells using the CliniMACS TCR α/β-biotin and CD19 Systems.
CliniMACS® System
DeviceThe CliniMACS Cell Selection System is based on magnetic-activated cell sorting mechanism. The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures.
Incidence of grade III-IV acute graft-versus-host disease (GVHD)
Acute GVHD will be assessed and graded according to the Keystone Consensus Criteria for staging and grading of acute graft-versus-host disease.
Incidence of extensive chronic GVHD
Chronic GVHD will be assessed according to the current CIBMTR (Center for International Blood and Marrow Transplant Research) manual reflecting a grading system published by Sullivan KM (Sullivan 1981).
Incidence of graft failure
Graft failure - defined as failure to achieve ANC \> 500 /µL at Day +28 or initial neutrophil engraftment followed by a decline in ANC \< 500 /µL that is unresponsive to growth factor therapy (secondary graft failure).
Incidence of Treatment Related Mortality (TRM)
TRM - defined as death from any cause other than disease progression.
Time to neutrophil engraftment
The time to neutrophil engraftment is defined as the post-transplant day that is the first of 3 consecutive days with an absolute neutrophil count (ANC) of \>500/µL as assessed by CBC.
Time to platelet engraftment
The time to platelet engraftment is defined as the post-transplant day that is the first of 3 consecutive days with a platelet count ≥ 20,000/µL as assessed by complete blood count (CBC), without platelet support (transfusion) for 7 days.
Percentage donor chimerism using Short Tandem Repeat (STR)
Short tandem repeat (STR) analysis will provide the percentage donor chimerism at specific time points post-transplant.
Kinetics of lymphocyte reconstitution via immunophenotyping using flow cytometry
Lymphocyte reconstitution will be assessed at specific time points post-HSCT, expressed as the percentage of white blood cells comprised of T, B and NK cell subsets.
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