T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia

Patient Selection:

Inclusion Criteria:

- Diagnosis of Fanconi anemia

- Less than 65 years of age

- Karnofsky performance status of ≥ 70% or, for children < 16 years of age, Lansky Play
Score ≥ 50 - refer to Appendix III

- Presence of at least one of the following risk factors:

- Severe aplastic anemia (SAA) defined as: Aplastic anemia is defined as having at
least one of the following when not receiving growth factors or transfusions:

- platelet count <20 x 109/L

- absolute neutrophil count of <5 x 108/L

- hemoglobin <8 g/dL

- Myelodysplastic syndrome (MDS) or acute leukemia

- High risk genotype

- Adequate organ function defined as:

- Bilirubin, AST or ALT, ALP <5 x normal, Cardiac: left ventricle ejection fraction
(LEFV) ≥45% by ECHO

- Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For
children that are not able to cooperate with PFTs, a pulse oximetry with exercise
should be attempted. If neither test can be obtained it should be clearly stated
in the physician's note.

- Identification of a suitable donor for peripheral blood cells per match criteria found
in Section 5.

- Females of childbearing potential and males with partners of child-bearing potential
must agree to use of contraception for the duration of treatment and 4 months after
the transplant

- Able to provide written voluntary consent prior to the performance of any research
related tests or procedures with parental/guardian consent for minor (and assent as
appropriate)

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