PRIMARY OBJECTIVES:~I. To determine if the infusion of CD4+ T-cell-depleted hematopoietic cells from a haploidentical donor, following a non-myeloablative/ reduced-intensity preparative regimen is safe in patients with severe aplastic anemia (SAA).~II. To determine the feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product, as assessed by:~IIa. Ability to meet the minimum required CD34+ cell dose, and; IIb. Ability to meet the CD4+ T-cell depletion product release requirements.~SECONDARY OBJECTIVES:~I. To evaluate toxicities including type, frequency, severity, attribution, time course, and duration. (Safety/tolerability) II. To summarize and evaluate hematologic (neutrophil and platelet) recovery, including marrow failure. (Safety/tolerability) III. To estimate the incidence of infection and infectious disease related complications at 100 days. (Safety/tolerability) IV. To estimate the incidence of SAA related complications. (Safety/tolerability) V. To estimate the cumulative incidence of non-relapse mortality at 100-days, 1-year and 2-years post hematopoietic stem-cell transplantation (HCT). (Safety/tolerability) VI. To estimate the cumulative incidence of acute graft versus host disease (GvHD) (grades: II-IV, III-IV) at 100-days and chronic GvHD (grades: any, moderate-severe) at 6-months, 1-year and 2-years post HCT. (Safety/tolerability) VII. To estimate the overall survival probability at 100-days, 1-year and 2-years post HCT. (Survival/relapse) VIII. To estimate the disease-free survival probability at 100-days, 1-year and 2-years post HCT. (Survival/relapse) IX. To estimate the event-free survival probability at 100-days, 1-year and 2-years post HCT. (Survival/relapse) X. To estimate the cumulative incidence of disease relapse at 100-days, 1-year and 2-years post HCT. (Survival/relapse) XI. To describe response as categorized by graft failure, persistent post-immunosuppressant (IS) mixed chimerism, persistent IS-dependent mixed chimerism, complete chimerism. (Chimerism) XII. To summarize/characterize patient chimerism (percent of donor total nucleated and donor lineage specific cells) over time. (Kinetics)~EXPLORATORY OBJECTIVES:~I. To describe the ratio of donor to recipient de novo thymic T cells over the course of 2 years within the peripheral blood compartment.~II. To describe the ratio of donor to recipient regulatory T cells and regulatory B cells over the course of 2 years within the peripheral blood and bone marrow compartments.~III. To describe the tolerance status of donor and host-type T cells over the course of 2 years within the peripheral blood compartment.~IV. To describe the T-cell repertoire of donor- and host-type T cells over the course of 2 years within the peripheral blood compartment.~V. To describe the bone marrow niche and peripheral blood cytokine profile over time.~VI. To describe bone marrow progenitor chimerism over time.~OUTLINE:~Patients receive cyclophosphamide orally (PO) and intravenously (IV), pentostatin IV, anti-thymocyte globulin IV and undergo CD4+ T-cell depleted haploHCT on study. Patients also undergo bone marrow aspirate, bone marrow biopsy, and collection of blood samples at screening and follow-up.
This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not respond to treatment (refractory) or that has come back (recurrent). Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid. It may also lower the body's immune response. Pentostatin blocks a protein needed for cell growth. Anti-thymocyte globulin is an immunosuppressive drug can destroy immune cells known as T-cells. HaploHCT transfers blood-forming stem cells from a healthy partially-matched donor to a patient. Administering a regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin before haploHCT may help make room for the new, healthy cells and may reduce the risk of graft versus host disease.