Hereditary Homocysteine Remethylation Disorder
Conditions
Brief summary
This study aims to evaluate the safety, feasibility, and preliminary efficacy of autologous hematopoietic stem cell transplantation (ASCT) in the treatment of neurological damage associated with hereditary homocysteine remethylation disorders. Meanwhile, peripheral blood, cerebrospinal fluid, and related clinical samples will be prospectively collected before and after transplantation to dynamically monitor changes in immune reconstitution and neuroinflammatory biomarkers. The study intends to explore the impact of immune system resetting on disease progression and central nervous system immune microenvironment, providing evidence for subsequent precise patient stratification and optimized therapeutic strategies.
Interventions
OTHERAutologous Hematopoietic Stem Cell Transplantation
ASCT Regimen 1. Autologous hematopoietic stem cell collection Mobilization with chemotherapy plus cytokines: * Cyclophosphamide: 30 mg/kg/d, administered intravenously for 2 consecutive days. * G-CSF: 5-10 μg/kg/d subcutaneous injection for 5 consecutive days. Collection target: CD34+ cells ≥ 2×10⁶/kg; repeat leukapheresis permitted to meet target dose. 2. Conditioning Regimen: * Thiotepa: 5 mg/kg/d Day -7 * Fludarabine: 5 mg/kg/d Days -6 to -2 (5 total days) * Rituximab: 375 mg/m² Day -1 3. Stem cell infusion: Day 0 Infusion dose: ≥ 2×10⁶ CD34+ cells/kg
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 to 55 years, regardless of gender. 2. Comprehensive clinical, biochemical, and genetic diagnosis of hereditary homocysteine remethylation disorders. 3. Evidence of neurological involvement, including but not limited to gait disturbance, balance impairment, cognitive dysfunction, cerebral white matter lesions. 4. Prior standardized metabolic therapy (folic acid, vitamin B12, betaine) with suboptimal clinical response. 5. Persistent severe metabolic abnormality, i.e., sustained elevated homocysteine (\>50 umol/L). 6. Multidisciplinary consensus confirming lack of effective alternative therapies and ongoing risk of disease progression. 7. Voluntary participation, signed informed consent, adequate treatment adherence, and willingness to complete follow-up assessments.
Exclusion criteria
1. Prior hematopoietic stem cell transplantation or other cell transplantation. 2. Severe dysfunction of critical organs (heart, lung, liver, kidney) deemed incompatible with study treatment by investigators. 3. Active, uncontrolled infection. 4. Active tuberculosis, hepatitis B, hepatitis C, HIV infection, or other infectious diseases judged inappropriate for enrollment by investigators. 5. Active malignancy or prior malignant history that may confound safety and efficacy evaluations. 6. Severe underlying comorbidities likely to interfere with study treatment or outcome assessment. 7. Severe psychiatric disorder or cognitive impairment with poor adherence precluding completion of treatment and follow-up. 8. Pregnant or lactating females, or participants unwilling to use effective contraception throughout the study period. 9. Severe hypersensitivity to any study-related medication or intervention. 10. Participation in other interventional clinical trials within the past 4 weeks or ongoing observation period of another clinical trial. 11. No documented disease progression within the preceding 12 months. 12. Minimal neurological symptoms with no meaningful impact on activities of daily living and low short-term progression risk per investigator assessment. 13. Established standard therapies proven to alter natural disease history with stable disease and satisfactory therapeutic response. 14. End-stage disease with extensive irreversible neurological impairment (severe motor/cognitive failure or multi-organ dysfunction) with minimal expected therapeutic benefit. 15. Any other conditions deemed unsuitable for study participation by investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: Incidence of adverse events within 100 days post ASCT | 100 days post ASCT |
Secondary
| Measure | Time frame |
|---|---|
| Success rate of autologous hematopoietic stem cell collection | Within 3 days after initiation of stem cell collection |
| Time to neutrophil engraftment | 28 days post ASCT |
| Time to platelet engraftment | 1 year post ASCT |
| 1-year overall survival post ASCT | 1-year post ASCT |
| Changes in neurological functional scores | from baseline to 1 year after ASCT |
| Changes in MRI lesions | from baseline to 1 year after ASCT |
| PET-CT findings | from baseline to 1 year after ASCT |
| Kinetics of peripheral immune reconstitution | from baseline to 1 year after ASCT |
| Changes in inflammatory and neuronal injury biomarkers | from baseline to 1 year after ASCT |
Countries
China
Contacts
CONTACTJiang erlie
CONTACTcao yigeng
Outcome results
None listed