Lupus Nephritis
Conditions
Brief summary
In this study, we aimed to evaluate the long term efficacy, remission, survival and safety of autologous hematopoietic stem cell transplantation in patients with refractory lupus nephritis. This is an single arm, non-randomized study. Patients who were diagnosed with relapsed and refractory lupus nephritis would included in this study. Refractory lupus nephritis is defined as no response to at least one type of immunosuppressant therapy (including corticosteroids, cyclophosphamide, tacrolimus, mycophenolate mofetil and cyclosporine) for more than six months, or relapse during the period maintenance therapy with kidney pathological transformation or persistently positive antibodies. Close observation was carried out at stem cell harvest, at transplantation, at 3, 6, 12, 18, and 24 months and then once a year after autologous stem cell transplantation. 20-30 cases will be included in this study.
Detailed description
Treatment plan: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was administered when the level of peripheral leucocytes was \< 1×109/L. Peripheral leukocyte counts were monitored, and harvesting was performed when the peripheral white blood cell level rebounded (usually 11 days after cyclophosphamide). The target acquisition was CD34+ cells \> 2×10\^6/kg and mononuclear cells \> 2×10\^8/kg. The graft was preserved at a temperature of -196 ℃ for further use. The conditioning regimen consisted of intravenous cyclophosphamide (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose of cyclophosphamide and ATG could be reduced according to the patients' condition. Methylprednisolone (80-500 mg/day) was administered through intravenous drip at the same time with ATG to reduce anaphylaxis. The incidence of drug-related complications was decreased by hyperhydration (the volume of infusion liquid is 50 ml/kg/day), urine alkalization (infusion of sodium bicarbonate 250ml/day), and anti-emetic medication. G-CSF (0.5 μg/kg/d) was administered to each patient beginning the day after stem cells reinfusion until the level of absolute peripheral neutrophil count was consecutively higher than 1.0 × 10\^9/L.
Interventions
PROCEDUREAutologous hematopoietic stem cell transplantation
Stem cell mobilization and collection: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was administered when the level of peripheral leucocytes was \< 1×109/L. Peripheral leukocyte counts were monitored, and harvesting was performed when the peripheral white blood cell level rebounded . Conditioning and reinfusion of stem cells: The conditioning regimen consisted of intravenous cyclophosphamide (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose of cyclophosphamide and ATG could be reduced according to the patients' condition.
Sponsors
Nanjing University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Diagnosed with relapsed and refractory lupus nephritis; 2. Ages from 14 - 45 years old; 3. Serum creatinine \< 2mg/dl; 4. Alanine aminotransferase \< 2 times of normal upper limit; 5. Left ventricular ejection fraction \> 50%; 6. Subjects (or their legal representatives) must signed an informed consent document.
Exclusion criteria
* 1\. Active infection; 2. Known or suspected hypersensitivity to CTX or ATG; 3. Subjects suffering from uncontrolled or severe cardiovascular disease; 4. Subjects suffering from serious physical disease and mental illnesses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal remission rate | seven years | The curative effect on the kidney was defined as follows: complete remission: proteinuria\< 0.4 g/24 h, red blood cell (RBC) \< 3/HP in urine sediment, serum albumin \> 3.5g/dl and serum creatinine \< 1.24 mg/dl; partial remission: 50% baseline \< decrease of proteinuria \< 3.5 g/24 h, serum albumin \>30g/L and serum creatinine \< 1.24 mg/dl, no remission (NR): failed to achieve partial remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| renal survival | seven years | the time from treatment start to dialysis. |
| treatment related mortality | 3 months | patients who dies in 3 months after treatment start. |
Countries
China
Outcome results
None listed