Autologous Stem Cell Transplant in Multiple Sclerosis

Patient with Multiple Sclerosis who meets the eligibility criteria will be enrolled in the intervention study. It is proposed that a total of 60 patients would be enrolled into 2 sequential cohorts. Patients would be assigned to one of the available cohorts (in a block of 30:30 fashion), unless there is a clear medical reason determined by the transplant physician that they should be treated with a particular regimen (eg: history of allergic reaction to one of the drugs). The intervention involves patients being admitted into hospital to mobilise their Peripheral Blood Stem Cells using a single dose 2g/m2 cyclophosphamide being given as an inpatient. Intravenous fluids will be prescribed to run concurrently with cyclophosphamide as per current standard practice in the Haematology Unit for malignant conditions and patients will be reviewed by the medical team daily. The following day once the cyclophosphamide has being given, patients will be discharged from the ward. Prior to discharge, daily granulocyte stimulating factor (GCSF) 10mcg/kg/day is commenced (24hrs after completion of cyclophosphamide) and subsequent doses will be administered (at home) and continue until stem cell collections are complete. Patients are contacted by the transplant coordinator at the beginning of the week after being discharged to check whether they are having any difficulties injecting themselves and overall physical and mental wellbeing. Patients will then start leukapheresis (stem cell collection) once their peripheral blood CD34+ count is >10/uL until a minimum CD34+ collection. Patients may require a vascath insertion on the day prior to leukapheresis if venous access is not adequate – this would require a second consent form as per standard practice in the Haematology Department. Patients return for medical review as determined by the treating transplant physician subject to the patients level of wellbeing. After a clinically appropriate time period following the collection of stem cells, the patient is re-hospitalised to undergo the transplantation procedure. The procedure for this study involves been admitted into hospital for the administration of one of two regimens; Cyclophosphamide/Anti-Thymocyte Globulin (ATG) or Carmustine, Etoposide, Cytarabine and Melphalan with ATG 1 week prior to reinfusing their own stem cells to ‘grow’ a new immune system. Cohort 1: a daily dose of Cyclophosphamide at 50mg/kg is administered intravenously on Day -5, Day -4, Day -3, Day -2 with intravenous fluids prescribed to run concurrently. A daily intravenous ATG will also be given at the following doses: 0.5mg/kg on Day -5, 1mg/kg on Day -4, 1.5mg/kg on Day-3, Day-2 and Day -1 (total dose 6mg/kg) with methylprednisolone given intravenously at1mg/kg as premedication prior to every dose of ATG. Cohort 2: Carmustine given intravenously at 300mg/m2 on Day -6 followed by a daily intravenous ATG will also be given at the following doses: 0.5mg/kg on Day -5, 1mg/kg on Day -4, 1.5mg/kg on Day-3, Day-2 and Day -1 (total dose 6mg/kg) with methylprednisolone given intravenously at1mg/kg as premedication prior to every dose of ATG. In addition, cytosine arabinoside intravenously 200mg/m2/day daily from Day -5 to Day -2 and etoposide intravenously at 200mg/m2/day daily from Day -5 to Day -2 plus one dose of melphalan intravenously at 140mg/m2 on Day -1 Following Autologous Haematopoietic Stem Cell Transplantation (AHSCT), supportive therapies such as blood/platelet transfusions will be given intravenously depending on the results of blood tests. Prophylactic anti-microbials such as Bactrim, fluconazole and valaciclovir will also be used. It is anticipated that the duration of dosing of anti-microbials up to 3 months post-stem cell reinfusion depending on the wellbeing of the patient. Beginning on day +7, daily per oral prednisone at 0.5mg/kg (or IV methylprednisolone 0.5mg/kg daily) will be given for 5 days then 0.25mg/kg for 5 days then 10mg for 5 days then 5mg for 5 days as prophylaxis for serum sickness. If serum sickness develops, the same medication will be given however at treatment doses and will commence with 1mg/kg of prednisone orally and weaned as per physician discretion. All patients will have standardised follow up assessment visits as per post-transplant standard of care ranging from weekly, fortnightly to monthly depending on their wellbeing in the first 100 days post AHSCT, and for specific clinical trial outcome assessment at 3, 6, 12, 24 months and subsequently yearly, up to 10 years.