Haploidentical Donor Hematopoietic Cell Transplantation for Patients With Severe Aplastic Anemia
St. Jude Children's Research Hospital
Summary
This study is a prospective, single center phase II clinical trial in which patients with Severe Aplastic Anemia (SAA) ) will receive a haploidentical transplantation. The purpose of this study is to learn more about newer methods of transplanting blood forming cells donated by a family member that is not fully matched to the patient. This includes studying the effects of the chemotherapy, radiation, the transplanted cell product and additional white blood cell (lymphocyte) infusions on the patient's body, disease and overall survival. The primary objective is to assess the rate of engraftment at 30 days and overall survival (OS) and event free survival (EFS) at 1 year post-hematopoietic cell transplantation (HCT). Primary Objectives * To estimate the rate of engraftment at 30 days after TCR αβ+ T-cell-depleted graft infusion in patients receiving a single dose of post graft infusion cyclophosphamide. * To estimate the overall survival and event free survival at 1-year post transplantation. Secondary Objectives * To calculate the incidence of acute and chronic GVHD after HCT. * To calculate the rate of secondary graft rejection at 1-year post transplantation * To calculate the cumulative incidence of viral reactivation (CMV, EBV and adenovirus). * To describe the immune reconstitution after TCR αβ+ T-cell-depleted graft infusion at 1 month, 3 months, 6 months, 9 months, and 1 year. Exploratory Objectives * To longitudinally assess the phenotype and epigenetic profile of T-cells in SAA patients receiving HCT for SAA. * To assess the phenotype and epigenetic profile of T-cells in DLI administered to SAA patients post HCT. * To longitudinally assess CD8 T cell differentiation status in SAA patients using an epigenetic atlas of human CD8 T cell differentiation. * To examine the effector functions and proliferative capacity of CD8 T cells isolated from SAA patients before and after DLI. * Quantify donor derived Treg cells at different time points in patients received HCT. * Determine Treg activation status at different stages after HCT. * Are specific features of the DLI product associated with particular immune repertoire profiles post-transplant? * How does the diversity and functional profile of the DLI product alter the response to pathogens in the recipient? * Do baseline features of the recipient's innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles?
Description
Immunosuppressant therapy (IST) is the main treatment for SAA for patients who do not have an HLA-matched sibling donor available for transplant. But some patients with SAA do not respond to IST and some others relapse after IST. HCT using an unrelated but HLA-matched donor is the only curative option for these patients but many patients lack a suitable HLA-matched donor. St Jude is trying to increase donor options for these patients by using novel therapeutic strategies by combining two widely used of GVHD prophylaxis methods: i) selective T cell depletion and ii) use of post-transplant cyclo…
Eligibility
- Age range
- Up to 21 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria for Transplant Recipient 1. Age less than or equal to 21 years at time of enrollment. 2. Confirmed diagnosis of SAA or a single lineage cytopenia (a) SAA or single lineage cytopenia will be defined as follows: * i. Bone marrow cellularity \< 25% or hypocellular marrow for age, AND * ii. One or more of the following (in peripheral blood): (i) Neutrophils \< 0.5 x10\^9/L (ii) Platelets \< 20 x10\^9/L, or platelet transfusion dependence (iii) Hemoglobin \<8g/dL, or red blood cell transfusion dependence 3. Does not have a suitable HLA-matched sibling donor (MSD) or vo…
Interventions
- DrugAnti-Thymocyte Globulin (Rabbit)
Given intravenously (IV)
- DrugFludarabine
Given intravenously (IV)
- DrugCyclophosphamide
Given intravenously (IV)
- DrugMesna
Given intravenously (IV)
- DrugG-CSF
Filgrastim is a human granulocyte colony-stimulating factor (G-CSF), produced by recombinant DNA technology. Dosage and Route of Administration: 5mcg/kg subcutaneous or intravenous daily until ANC \>2000 for 2 consecutive days, or as clinically indicated
- RadiationTotal Lymphoid Irradiation (TLI)
TLI will be given at 800 cGy total dose in 4 fractions.
- Device
Location
- St. Jude Children's Research HospitalMemphis, Tennessee