Multiple Sclerosis
Conditions
Brief summary
Autologous hematopoietic stem cell transplantation (aHSCT) is the only treatment for refractory autoimmune diseases capable of inducing long-term, drug-free and asymptomatic remission. Over the past two decades, aHSCT has been used to treat inflammatory autoimmune disease of the CNS. Patients with relapsing-remitting multiple sclerosis benefit from aHSCT treatment. However, a certain percentage of patients still experience recurrence 3 or 5 years after transplantation. Therefore, exploration of conditioning regimens will drive therapeutic advances in aHSCT in autoimmune diseases of the CNS.
Interventions
PROCEDUREAutologous haemopoietic stem cell transplantation
Immuno-ablation and autologous CD34 selected hematopoietic stem cell transplantation (HSCT). Stem cell mobilization with cyclophosphamide 2g/m2 and filgrastim 10 ug/kg/d x 5 day. Stem cell collection with cobe cpectra stem cell purification with Miltenyi CliniMACS Stem cell transplant conditioning with busulphan 3.2 mg/kg ; fludarabine 30mg/m2 or cladribine 10mg ；cytarabine 1-2g/m2 or idarubicin 8mg/m2；cyclophosphamide 40mg/kg followed by CD34 selected autologous hematopoietic stem cell transplant.
Sponsors
Tianjin Medical University General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-60 years; 2. Diagnosed multiple sclerosis with relapses or progression and sustained accumulated impairment by a neurologist expert in the field; 3. EDSS score of 3-6 (including 3 and 6); 4. EDSS cerebellar functional score ≥ 3 or EDSS pyramidal functional score ≥3； 5. Evidence of current disease activity; 6. If a patient has previously received a cytotoxic agent (mitoxantrone, cyclophosphamide etc.) they must have normal bone marrow morphology and cytogenetics before being considered eligible for this study ; 7. No evidence of hepatic inflammation or fibrosis;
Exclusion criteria
1. Patients with evidence of myelodysplasia or other non-autoimmune cytopenia; 2. Patients having received a cytotoxic agent within one month of enrolling in this study; 3. Patient with any active or chronic infection (herpes simplex virus, varicella-zoster virus, cytomegalovirus, EB virus, human immunodeficiency virus, hepatitis virus, syphilis, etc.); 4. Patients having received a cytotoxic agent within one month of enrolling in this study; 5. Patients with a malignant tumor currently or within the last 5 years; 6. Patients with cardiac, renal, pulmonary, hepatic or other organ impairment; 7. Patients whose life expectancy is severely limited by another conditions; 8. Pregnancy or risk of pregnancy; 9. Patients unable to give written informed consent in accordance with research ethics board guidelines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3 year MS activity free survival | 3 year follow-up post transplant | The events for the primary outcome are: clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, or sustained progression of EDSS score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transplant related morbidity | 3 years | Rate of transplant related events. |
| Transplant related mortality | 3 years | Rate of transplant related death. |
| Time to MS treatment failure | 3 years | Disease activity and disability will be assessed with clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, or sustained progression of EDSS score and quality of life. |
| Hematopoietic reconstitution following transplant | 3 years | Rate of hematopoietic reconstitution following transplant. |
| Imaging changes associated with the disease activity | 3 years | Imaging changes include: new or enlarging T2-weighted lesion count and new T1-weighted lesion count at all scans after baseline; T2-weighted lesion volume; Gd-enhanced lesion count and volume; and total volume of non-enhancing T1-weighted lesions on all MRI scans. |
| Immune reconstitution following transplant | 3 years | Rate of immune reconstitution following transplant. |
Contacts
Primary ContactQiang Liu, M.D.,Ph.D
Outcome results
None listed