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.
A phase II trial of a reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for idiopathic severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria (PNH), acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT) utilizing population pharmacokinetic (popPK)-guided individual dosing of pre-transplant conditioning and differential dosing of low dose total body irradiation based on age, presence of myelodysplasia and/or clonal hematopoiesis.
• 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