Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation in patients with inherited bone marrow failure (BMF) disorders to eliminate the need for routine graft-versus-host disease (GVHD) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.


Eligibility Criteria:
Patient Selection:

Inclusion Criteria:

For FA patients:

* Diagnosis of Fanconi anemia

  * Age \<65 years of age
* Has one of the following risk factors:

  * Severe aplastic anemia (SAA)
  * Myelodysplastic syndrome (MDS)
  * High risk genotype
  * Immunodeficiency associated with history of recurrent infections
* Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age

  * Adequate pulmonary, cardiac and liver function
  * Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care

For TBD patients:

• Diagnosis of TBD

* Age \<70 years of age
* Has one of the following risk factors:
* Severe aplastic anemia (SAA)
* Myelodysplastic syndrome (MDS)
* Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score

  ≥ 50% for patients \<16 years of age
* Adequate pulmonary, cardiac and liver function
* Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care

Exclusion Criteria:

* Pregnant or breastfeeding as the treatment used in this study are Pregnancy Category D. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
* Active, uncontrolled infection within 1 week prior to starting study therapy
* Malignant solid tumor cancer within previous 2 years

Donor Selection (Inclusion Criteria): meets one of the following match criteria:

* an HLA-A, B, DRB1 matched sibling donor (matched sibling)
* an HLA-A, B, DRB1 matched related donor (other than sibling)
* a related donor mismatched at 1 HLA-A, B, C and DRB1 antigen
* 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor per current institutional guidelines Patients and donors are typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. If a donor has been selected on the basis of HLA-A, B, C and DRB1 typing as above, preference will be made for donors matched at the HLA-C locus.
* Body weight of at least 40 kilograms and at least 12 years of age
* Willing and able to undergo mobilized peripheral blood apheresis
* In general good health as determined by the medical provider
* Adequate organ function defined as:

  * Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
  * Hepatic: ALT \< 2 x upper limit of normal
  * Renal: serum creatinine \< 1.8 mg/dl
* Performance of a donor infectious disease screen panel including CMV Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV 1/2 Antibody, HTLVA 1/2 Antibody, Treponema, and Trypanosoma Cruzi (T. Cruzi) plus HBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of and risks factors for infection with Zika virus, or per current standard institutional donor screen - must be negative for HIV and active hepatitis B
* Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
* Voluntary written consent (parent/guardian and minor assent, if \< 18 years) prior to the performance of any research related procedure