MT2023-20: Hematopoietic Cell Transplant With Reduced Intensity Conditioning and Post-transplant Cyclophosphamide for Severe Aplastic Anemia and Other Forms of Acquired Bone Marrow Failure.

Inclusion Criteria:

• Idiopathic Severe Aplastic Anemia (SAA), characterized by one of the following:

1. Refractory cytopenia(s), with 1+ of the following:

2. Platelets <20,000/uL or transfusion dependent

3. Absolute neutrophil count <500/uL without hematopoietic growth factorsupport

4. Absolute reticulocyte count <60,000/uL AND bone marrow cellularity <50% (with < 30% residual hematopoietic cells)

5. Early myelodysplastic features (bone marrow (BM) blasts <5%), without historyof MDS/AML pre-treatment.

6. Idiopathic SAA with post-HCT graft failure (blood/marrow donor chimerism <5%)requiring a 2nd allogeneic HCT

• Paroxysmal Nocturnal Hemoglobinuria (PNH), including AA-PNH overlap syndrome,acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT), characterized by one of the following:

1. Refractory cytopenia(s), with 1+ of the following:

2. Platelets <20,000/uL or transfusion dependent

3. Absolute neutrophil count <500/uL without hematopoietic growth factorsupport

4. Absolute reticulocyte count <60,000/uL or red cell transfusion dependentAND Bone marrow evidence of 1 to 3-lineage aplasia OR peripheral blood PNHclone >/= 10%

5. Early myelodysplastic features (bone marrow (BM) blasts <5%) without history ofMDS/AML pre-treatment.

6. Idiopathic PNH, aPRCA, or aAT with post-HCT graft failure (blood/marrow donorchimerism <5%) requiring a 2nd allogeneic HCT

• Adequate organ function within 30 days of conditioning regimen

Exclusion Criteria:

• Pregnant, breastfeeding or intending to become pregnant during the study. Persons ofchildbearing potential must have a negative pregnancy test (serum or urine) within 7days of the start of treatment

• Uncontrolled infection

• Evidence of moderate or severe portal fibrosis or cirrhosis on biopsy

• Known allergy to any of the study components

• Prior radiation therapy deemed excessive by radiation therapist for proposed lowdose TBI exposure on this protocol

• Diagnosis of an inherited bone marrow failure disorder such as Fanconi anemia,Telomere biology disorder, or Schwachman-Diamond syndrome, unless reviewed by theprincipal investigator and deemed appropriate for this approach (e.g. GATA2deficiency)

• Advanced myelodysplastic syndrome (MDS; BM blasts >5%) or acute myeloid leukemia

• Psychiatric illness/social situations that, in the judgement of the enrollingInvestigator, would limit compliance with study requirements

• Other illness or a medical issue that, in the judgement of the enrollingInvestigator, would exclude the patient from participating in this study