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.

Conditions: Severe Aplastic Anemia; Acquired Amegakaryocytic Thrombocytopenia; Acquired Pure Red Cell Aplasia; Paroxysmal Nocturnal Hemoglobinuria

Summary: 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.


Eligibility criteria:
inclusion criteria: * idiopathic severe aplastic anemia (saa), characterized by one of the following: 1. refractory cytopenia(s), with 1+ of the following: 1. platelets \<20,000/ul or transfusion dependent 2. absolute neutrophil count \<500/ul without hematopoietic growth factor support 3. absolute reticulocyte count \<60,000/ul and bone marrow cellularity \<50% (with \< 30% residual hematopoietic cells) 2. early myelodysplastic features (bone marrow (bm) blasts \<5%), without history of mds/aml pre-treatment. 3. 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: 1. platelets \<20,000/ul or transfusion dependent 2. absolute neutrophil count \<500/ul without hematopoietic growth factor support 3. absolute reticulocyte count \ /= 10% 2. early myelodysplastic features (bone marrow (bm) blasts \<5%) without history of mds/aml pre-treatment. 3. 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

Keywords: hct ric saa ptcy aat aprca