Clinical Trial of Upfront Haploidentical or Unrelated Donor BMT to Restore Normal Hematopoiesis in Aplastic Anemia

Inclusion Criteria: 1. Age 3 years to 75 years 2. Confirmed diagnosis of acquired SAA defined as: a. Bone marrow cellularity \< 25% or variable marrow cellularity but with \< 30% residual hematopoietic cells deemed HYPOcellular for age AND b. Two (2) out of 3 of the following (in peripheral blood). i. Neutrophils \< 0.5 x109/L ii. Platelets \< 20 x109/L iii. Reticulocyte count \< 20 x109/L (\< 60 x 109/L using an automated analysis) 3. No suitable fully matched related donor as per Investigator's discretion (6/6 match for HLA A and B at intermediate or high-resolution and DRB1 at high-resolution using deoxyribonucleic acid \[DNA\]-based typing) available. 4. Available donor as defined in the protocol. 5. Participant and/or legal guardian must sign informed consent. 6. Adequate organ function defined by institutional transplant standards or defined as below: 1. Cardiac: Left ventricular ejection fraction (LVEF) at rest \> 40% with no clinical signs of cardiac failure. For participants aged \< 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or multigated acquisition (MUGA) may be substituted for LVEF. 2. Hepatic: Total bilirubin \< 2.0 mg/dL unless Gilbert's disease is present 3. Renal: For participants \> 13.0 years of age at the time of enrollment: estimated creatinine clearance (CrCl) \> 60 mL/minute (per institutional standard). For participants \< 13.0 years of age at enrollment: glomerular filtration rate (GFR) estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is \< 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m2. 4. Pulmonary: i. For participants \> 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO, corrected/adjusted for hemoglobin \[Hb\]) \> 50%, or Spirometry with forced expiratory volume 1 (FEV1) \> 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) \> 50% predicted. ii. For participants \< 13.0 years of age unable to perform pulmonary function tests (PFTs) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation \> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care \[e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%\]). 7. Karnofsky or Lansky performance status ≥ 60%. 8. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence. Exclusion Criteria: 1. Inherited bone marrow failure syndromes such as Fanconi anemia and short telomere syndromes must be ruled out according to center standards. It is recommended that functional testing for Fanconi Anemia (di-epoxybutane \[DEB\] chromosomal breakage analysis) and telomere length assessment be performed. If available, genetic panels for inherited bone marrow failure syndromes can be considered as an alternative to functional testing. 2. Clonal cytogenetic abnormalities consistent with pre-MDS or MDS on marrow examination (e.g., monosomy 7 and other MDS-defining changes per recent pathology guidelines). 3. Formal diagnosis of MDS by World Health Organization (WHO) 2022 or International Consensus Classification (ICC). 4. Recipient positive for HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, -DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) \>3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and immediately prior to initiation of recipient preparative regimen to ensure there is confirmation of no DSA to the selected donor when conditioning starts. 5. Prior desensitization attempt for HLA antibodies to chosen donor. Any intervention with the sole intent to reduce the level of HLA DSA, (e.g., plasmapheresis, intravenous immunoglobulin \[IVIG\], MMF, etc.) would constitute a desensitization attempt. 6. Prior treatment for SAA (e.g., immunosuppressive therapy using ATG, calcineurin inhibitors \[CNIs\], thrombopoietin receptor agonists or androgens). Short courses of steroids or IVIG that were not explicitly administered for SAA therapy will be allowed. 7. Prior allogeneic stem cell transplant. 8. Prior solid organ transplant. 9. Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin® (Sanofi) that would prohibit use for the participant as this study requires use of the Thymoglobulin® (Sanofi) preparation of ATG. 10. Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment. 11. Female participants who are pregnant, as detected using a pregnancy test as per institutional practice, or breast-feeding. 12. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent \> 5 years previously will be allowed. Cancer treated with curative intent ≤ 5 years previously will not be allowed unless approved by the Protocol Chairs and/or Protocol Officer. Of note, participants with seropositivity for the human immunodeficiency virus (HIV) may be considered if viral load is undetectable. Similarly, carriers of hepatitis B (HepB) or hepatitis C (HepC) may not have a detectable viral load of HepB virus or HepC virus. Participants with HIV that is well-controlled on combination antiretroviral therapy and no AIDS related complications within the past 12 months are eligible. Infections other than HIV: * Prior infections must be controlled * HepB participants are eligible if on effective suppressive therapy and otherwise meet inclusion/exclusion criteria * HepC participants are eligible if otherwise meet inclusion/exclusion criteria