Multi-omics Profiling of Patients With Aplastic Anemia Before and After CD7-CAR-T Therapy

Overview

Aplastic anemia (AA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and hypocellular bone marrow, with immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs) playing a central role in its pathogenesis. Although immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT) have improved survival, a significant proportion of patients remain refractory, relapse after treatment, or lack suitable donors for transplantation. Therefore, novel therapeutic strategies are urgently needed. Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in hematologic malignancies. CD7 is an early surface marker of T-lineage cells and is dispensable for T cell development and function, making it a promising therapeutic target. This exploratory study aims to investigate the molecular and cellular mechanisms of CD7-CAR-T therapy in AA patients by analyzing multi-omics changes before and after treatment. This is a prospective, single-center, single-arm, open-label study enrolling patients with relapsed or refractory severe aplastic anemia. Participants will receive autologous CD7-CAR-T cells following lymphodepletion. Multi-omics profiling, including genomics, transcriptomics, proteomics, and immunophenotyping, will be performed on patient samples before and after infusion. The primary objective is to explore dynamic molecular changes associated with treatment response and disease progression. Secondary objectives include safety evaluation and preliminary assessment of efficacy. Findings from this study may provide mechanistic insights into CD7-CAR-T therapy in AA and inform the development of innovative immunotherapies for bone marrow failure syndromes.

This is a single-center, single-arm, prospective clinical study evaluating the safety and efficacy of CD7-directed CAR-T cell therapy in adult patients with refractory or relapsed severe aplastic anemia (SAA). SAA is an acquired bone marrow failure disorder characterized by pancytopenia and hypocellular marrow without malignant infiltration. Standard immunosuppressive therapy (IST) has improved survival, but approximately 30% of patients fail initial treatment, and relapse or progression to myelodysplastic syndrome or acute myeloid leukemia remains a clinical challenge. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves outcomes for younger patients but is limited by donor availability and graft-versus-host disease risks. Eligible participants are adults (≥18 years) with ECOG performance status 0-1, life expectancy ≥3 months, and refractory or relapsed SAA after IST, or ineligible for, lacking access to, or refusing allo-HSCT. Key laboratory criteria include creatinine ≤2.5× upper limit of normal, total bilirubin ≤3× ULN, ALT and AST ≤3× ULN, and baseline oxygen saturation ≥90%. Patients must have suitable venous access for leukapheresis and comply with contraception requirements if of reproductive potential. Exclusion criteria include active infections, severe cardiovascular disease, recent malignancy (except certain adequately treated cancers), pregnancy or breastfeeding, HIV, HBV, HCV above specified thresholds, or hypersensitivity to CAR-T components. The study consists of four stages: patient screening and enrollment; preconditioning including leukapheresis, CAR-T cell manufacture, and chemotherapy; CD7-CAR-T cell infusion with inpatient monitoring; and long-term follow-up. Patients receive a lymphodepletion regimen with fludarabine and cyclophosphamide prior to a single infusion of CD7-CAR-T cells at 3×10\^6 cells/kg. Safety assessments, including monitoring for cytokine release syndrome and other adverse events, will be conducted closely during hospitalization. Efficacy assessments include complete blood counts, bone marrow evaluation, and multi-omics analysis of immune cell subsets and cytokine profiles at defined intervals. Participants will be followed up for up to 3 years post-infusion, with intensive monitoring in the first 6 months and periodic assessments thereafter to evaluate disease status, CAR-T cell persistence, long-term safety, and quality of life. The primary endpoint is overall response rate (ORR), with secondary endpoints including progression-free survival (PFS), overall survival (OS), and safety outcomes. This study aims to provide the first evaluation of CD7-CAR-T therapy in refractory or relapsed SAA patients, potentially offering a novel therapeutic option for this high-risk population.