Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

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 theperformance 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 ofany study related procedures not part of standard medical care

Exclusion Criteria:

• Pregnant or breastfeeding as the treatment used in this study are Pregnancy CategoryD. Females of childbearing potential must have a negative pregnancy test (serum orurine) 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 institutionalguidelines Patients and donors are typed for HLA-A and B using serological ormolecular techniques and for DRB1 using high resolution molecular typing. If a donorhas been selected on the basis of HLA-A, B, C and DRB1 typing as above, preferencewill 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 ofnormal 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) plusHBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of andrisks factors for infection with Zika virus, or per current standard institutionaldonor screen - must be negative for HIV and active hepatitis B

• Not pregnant - females of childbearing potential must have a negative pregnancy testwithin 7 days of mobilization start

• Voluntary written consent (parent/guardian and minor assent, if < 18 years) prior tothe performance of any research related procedure