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Treatment Protocols

Dr. Yaakov Rowe, Shaarei Zedek medical center in Jerusalem, Israel

Preparation for transplantation in Sharei Zedek Hospital consisted of consultations with our specialists on the neurological part Dr. Ariel Miller (neurological re-evaluation), while Dr. Miller is to approve the patient's candidacy for HSCT.
The technical part with Prof. Yaakov Rowe and the HSCT department. Performance of necessary examinations (blood tests, lung function, heart function tests, etc.). 
Start of Fligrastim shoots (usually done by yourself, 5 days before harvesting) - it will increase the production of stem cells in patient's body. Introduction of Hickman catheter and stem cells harvesting. 
This part is will normally take 7 days, depending on hospital schedule and harvesting results. 

Chemotherapy itself continued for 6 days and consists of four drugs: BCNU, Cytarabine, Etoposide, and Melphalan with subsequent ATG (polyclonal rabbit antibodies against T lymphocytes). The so-called BEAM-ATG protocol. 
Re-infusion of previously collected stem cells (so-called day 0).
The time from re-infusion of stem cells to the day of engraftment is approximately 2-3 weeks. All kinds of supportive treatments would be used to bridge you over this time. 

This part will normally take 4 weeks.

After recovery one can be discharged from the hospital for a continuation of follow-up in an outpatient setting while visiting the clinic once a week for a scheduled check-up. Normally a patient will be released for a flight home after 2 weeks.
After strong immunosuppression during this transplantation, certain prophylactic treatments (TMP/SMX and Acyclovir) should be taken for 3 months.

We encourage our patients to stay in touch and update our medical team with post-HSCT test results.

Dr. Igor Resnick, Santa Marina Medical Center in Varna, Bulgaria

Screening neurologist (MS expert) and transplanter visits. The patient is required to provide the specialists with full medical history, neurological history, and all relevant examinations. According to provided information and professional reevaluation in ‘Santa Marina’ doctors will decide if the candidate can benefit from the treatment and will be excepted.
Pretransplant tests: blood workup (CBC, chemistry, serology for infections, blood group, chemistry, etc.), functional testing (spirography, EchoCG, and/or MUGA, imaging if indicated, etc.).
Functional neurological status, which includes EDSS, 25 feet walking test, cognitive evaluation.
MRI with/without gadolinium contrast as well as lumbar puncture for CSF tests (oligoclonal bands) will be considered (optional), to measure future progress in long-term post-BMT period.
Mobilized hematopoietic stem cell collection will be performed from peripheral blood after mobilization with G-CSF (filgrastim or neupogen) given as subcutaneous injections for 5 days. Usually, 1-2 collection (apheresis) procedures are enough. An alternative option is BMT bone marrow collection from pelvis (iliac crest). This procedure will be performed combined with topical anesthesia and general sedation (anesthesiologist team). Usually from 600 ml to 1000 ml bone marrow will be harvested and conserved (frozen). It is minimally traumatic and even hospitalization is not necessary.
Central venous access will be necessary and inserted by a specialist in angiology for constant IV access.
Pre-transplant evaluation and preparation is 7-10 days.

Pre-transplant conditioning before transplantation takes 7 days and will include two immunosuppressive chemotherapeutic drugs (fludarabine and cyclophosphamide) and an ATG (anti-thymocyte globulin) Thymoglobuline, polyclonal antibodies with a strong immunosuppressive effect established for HSCT for MS given together with corticosteroids as premedication and as an anti-inflammatory agent. 

After conditioning pre-collected hematopoietic stem cells will be re-infused intravenously (day 0). 
This treatment causes deep suppression of immune system and makes a patient sensitive to infections, which can need treatment with appropriate antibiotics. Other side effects are associated with mucositis, which is not often and usually not pronounced after mentioned pretreatment. Mucositis can cause pain and will be treated with pain killers. Low platelets or hemoglobin count due to chemotherapy sometimes make blood products transfusions indicated. From day +6 after transplantation stimulation of bone marrow with G-CSF, and usually 10-14 days after transplantation blood tests became close to normal (engraftment). At this time the patient will be discharged from the unit.
This part will normally take 3 weeks, mostly while admitted to the hospital.

Post-transplant course follow-up (an optimal is about 1-2 months after discharge):
The resetting of the immune system takes several months. The patient will need close enough follow-up and anti-infective prophylactic treatment (standard is 3 months) with 1-2 doctor’s visits per week and blood work-up.
We would like to make milestone post-transplant evaluation in 1-2, 6-7, and 11-13 months after transplantation with a proposal of extension. Control MRI and CSF (optional) analysis are recommended in a year from HSCT. We kindly ask our international patients to send us the results or materials for analysis.

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