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:

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

Platelets <20,000/uL or transfusion dependent
Absolute neutrophil count <500/uL without hematopoietic growth factor support
Absolute reticulocyte count <60,000/uL AND bone marrow cellularity <50% (with < 30% residual hematopoietic cells)
Early myelodysplastic features (bone marrow (BM) blasts <5%), without history of MDS/AML pre-treatment.
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:

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

Platelets <20,000/uL or transfusion dependent
Absolute neutrophil count <500/uL without hematopoietic growth factor support
Absolute reticulocyte count <60,000/uL or red cell transfusion dependent AND Bone marrow evidence of 1 to 3-lineage aplasia OR peripheral blood PNH clone >/= 10%
Early myelodysplastic features (bone marrow (BM) blasts <5%) without history of MDS/AML pre-treatment.
Idiopathic PNH, aPRCA, or aAT with post-HCT graft failure (blood/marrow donor chimerism <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 of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days 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 low dose 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 the principal investigator and deemed appropriate for this approach (e.g. GATA2 deficiency)
Advanced myelodysplastic syndrome (MDS; BM blasts >5%) or acute myeloid leukemia
Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements
Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study