Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

Inclusion Criteria36

• Patient Selection:
• For FA patients:
• Diagnosis of Fanconi anemia
• Age \<65 years of age
• Has one of the following risk factors:
• Severe aplastic anemia (SAA)
• Myelodysplastic features
• 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 features
• 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
• 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
• /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