Depleted Donor Stem Cell Transplant in Children and Adults With Fanconi Anemia After Being Conditioned With a Regimen Containing Briquilimab

Inclusion Criteria:

All patients must have:

1. Fanconi Anemia diagnosis as demonstrated by abnormal chromosome breakage studieswith increased sensitivity to mitomycin-C (MMC) or diepoxybutane (DEB) and at leastone mutation in a known Fanconi-associated gene

2. Bone marrow failure (defined by reduction in at least one cell line on two separateoccasions at least one month apart (e.g., platelet count of <100,000 per cubicmillimeter, hemoglobin <9 gm/dl and/or absolute neutrophil count (ANC) of <1000/mm)

3. Age of ≥2 years

4. Consenting ≥5/10 HLA-matched related or unrelated donor available for apheresis

5. Organ function defined as:

6. Serum Creatinine <2.0 mg/dL and corrected creatinine clearance/cystatin cL >60mL/min/1.73m^2 without dialysis

7. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), anddiffusing capacity of the lung for carbon monoxide (DLCO) corrected forhemoglobin and volume, >50% predicted by pulmonary function tests (PFTs)

8. For patients unable to cooperate for PFTs, criteria are no evidence of dyspneaat rest, no exercise intolerance, and no requirement for supplemental oxygenwith spO2 >93%

9. Shortening fraction of ≥29% or ejection fraction of ≥45% by echocardiogram

10. Serum total bilirubin of <4 x ULN

11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x ULN

12. Prothrombin time international normalized ratio (PT INR) and partialthromboplastin time (PTT) <1.5 x ULN

13. Life expectancy of at least 2 years

14. Patients of childbearing potential must be willing to use an effective contraceptivemethod for the duration of the peri-transplant conditioning through hematopoieticrecovery

15. Patients and/or parents or legal guardians must be able to provide written informedconsent and authorize use and disclosure of personal health information inaccordance with Health Insurance Portability and Accountability Act

Exclusion Criteria:

1. Patients with available and consenting 10/10 HLA-identical sibling donor forapheresis

2. Patients with any acute or uncontrolled infections at the time of enrollment,including bacterial, fungal or viral

3. Patients who are seropositive for HIV-I/II or HTLV-I/II.

4. Patients receiving any other investigational agents or other biological,chemotherapy, or radiation therapy within 14 days of enrollment

5. Patients with any active malignancies, myelodysplastic syndrome or other concernsfor high-risk bone marrow disease

6. Patients who received androgens in last 3 months

7. Pregnant or lactating women

8. Women who are nursing and do not wish to discontinue breastfeeding

9. Lansky/Karnofsky performance score <50%.

10. Any other medical condition or history that, in the opinion of the PrincipalInvestigator, could pose a significant safety risk to the participant or jeopardizethe integrity of the study

11. Patients who, in the opinion of the Principal Investigator, may not be able tocomply with the safety monitoring requirements of the study