The following overview shows day by day what is planned during the aHSCT treatment in Moscow. Here and there something can shift, but it certainly gives a good indication. The process lasts for 30 days. The transplant day is called “Day 0”. The days before are indicated as minus and then the days count up again.
The actual dates in this overview apply to the planned treatment of Tanja, Mama with MS. It is perfect for family and friends that stay at home, but also a good indication for future patients. The schedule can easily be taken over and entered from your own start date.
|~ CALENDAR ~|
|Weekday||Date||Day nr.||Schedule – aHSCT|
|Saturday||6 Oct.||.||Travel to Moscow|
|Sunday||7 Oct.||.||Day off|
|~ WEEK 1 ~|
|Monday||8 Oct.||D-15||Intake / Testing|
|Wednesday||10 Oct.||D-13||Testing / Day off?|
|Friday||12 Oct.||D-11||Mobilization day 1: stemcell injection (G-CSF) at 11pm and 3am
+ Methylprednisolone at 10-11am
|Saturday||13 Oct.||D-10||Mobilization day 2: stemcell injection (G-CSF) at 11pm and 3am
+ Methylprednisolone at 10-11am
|Sunday||14 Oct.||D-9||Mobilization day 3: stemcell injection (G-CSF) at 11pm and 3am
+ Methylprednisolone at 10-11am
|~ WEEK 2 ~|
|Monday||15 Oct.||D-8||Mobilization day 4: stemcell injection (G-CSF) at 11pm and 3am
+ Methylprednisolone at 10-11am
+ Hickman line 1 (neckline)
|Tuesday||16 Oct.||D-7||Harvesting / blood dialysis (5-6 hours, 2 million per kg./b.w.)|
|Wednesday||17 Oct.||D-8||Rest day (or extra harvesting when needed)
+ Hickman line 2 (neckline)
|Thursday||18 Oct.||D-5||Chemo day 1 (Cyclophosphamide: 50mg/kg/b.w.)|
|Friday||19 Oct.||D-4||Chemo day 2 (Cyclophosphamide: 50mg/kg/b.w.)|
|Saturday||20 Oct.||D-3||Chemo day 3 (Cyclophosphamide: 50mg/kg/b.w.)|
|Sunday||21 Oct.||D-2||Chemo day 4 (Cyclophosphamide: 50mg/kg/b.w.)|
|~ WEEK 3 ~|
|Monday||22 Oct.||D-1||Rest day|
|Tuesday||23 Oct.||Day 0||Stem cell transplantation day|
|Wednesday||24 Oct.||D+1||Rest day / Isolation|
|~ WEEK 4 ~|
|Friday||2 Nov.||D+10||Isolation + Rituximab infusion 1|
|Saturday||3 Nov.||D+11||Isolation / Recovery?|
|Sunday||4 Nov.||D+12||Recovery + Rituximab infusion 2|
|~ WEEK 5 ~|
|Tuesday||6 Nov.||D+14||Recovery / Discharge?|
|Wednesday||7 Nov.||D+15||Recovery / Discharge|
|Thursday||8 Nov.||D+16||Travel home|
Stemcell mobilization & harvesting of your own stemcells:
- The HSCT procedure that is being performed in Moscow is actually an aHSCT procedure. The ‘a’ stands for autologus, which means that a transplant will take place with your own body stem cells (not from a donor).
- Being able to harvest the stem cells, they must first be produced in large numbers by your own body. To achieve this, supportive stem cell injections will be given for 4 days to “mobilize” the stem cells, so to speak.
- G-CSF injections will be given twice a day at 11 pm and at 3 am. The drug is called Neupogen (Filgrastim) with a dose of 10 micrograms per kg body weight. G-CSF stands for granulocyte-colony stimulating factor.
- What actually happens is that the bone tissue will open up so that the pure newly created stem cells end up in the bloodstream. This process can cause bone pain and also headache, fever and other flu-like symptoms as most common side effects.
- After 4 days of injections, blood dialysis will take place on the following day (via a neck catheter which is placed during narcosis). In this way, the body’s own stem cells can be harvested from the blood and then stored (frozen) until the transplantation day.
- For a successful stem cell transplant, 2 million stem cells per kilogram of body weight have to be harvested. Harvesting through the dialysis machine usually takes 5 to 6 hours. If it turns out that insufficient stem cells have been harvested, harvesting will be resumed on the next scheduled rest day. This means that nothing has to be moved in the schedule.
- After the successful harvesting and storage of the stem cells, a (non-myelo ablative) chemotherapy of 4 days will take place by means of administering Cyclophosphamide.
- Actually, chemotherapy is the most important aspect of this treatment; a ‘hard reset’ of the immune system to completely eliminate the MS activity from the system. The white blood cells are brought to a complete zero point (including the ‘corrupt’ T and B cells that cause the MS symptoms/inflammatory).
- A total of 200 mg Cyclophosphamide per kilogram of body weight is administered over 4 days. So every day 50 mg / kg / b.w.
- During the chemo, supportive infusions and medications are administered (such as anti-viral, anti-fungal and for nausea).
- The most common side effects are: fever, nausea, vomiting, diarrhea, constipation, hair loss, oropharyngeal mucositis (mucosal inflammation in the mouth), pancytopenia (abnormally low blood count), haemorrhagic cystitis (abdominal pain and frequent and painful urination).
Stem cell transplantation:
- After resetting the immune system by means of chemotherapy and followed by a rest day, the previously harvested stem cells will then be transplanted back into the body. This day is characterized as “Day Zero”.
- These pure ‘baby stem cells’ will support the body to rebuild the best possible and new immune system. An immune system from the period when there was no MS activity in the body. It could be that by administering these stem cells, an extra benefit will occur that some lost functions will start to improve. However, such gains in performance must be seen as a ‘bonus’ and certainly not a guarantee. The stem cells can support the recovery, but the body has to do it themselves. Lost tissue / permanent damage can not be reversed.
- Most common side effects are: nausea, coughing, shortness of breath, vomiting, hot flashes, fever, shivering, high or low blood pressure.
- Following the transplant, at a certain moment the blood levels will drop drastically and the patient enters the neutropenic phase where the white blood cells are dangerously low to completely absent. At that point, the body no longer has an immune system. From a certain blood value the isolation period will be necessary.
- The isolation period takes an average of 9 to 10 days and starts approximately at D+1 / D+3 and lasts up to about D+8 / D+12.
- During isolation, the patient can not leave the room and the door remains closed. The suitcase and your clothes will be removed. Medical staff will clean the room daily, change bedding and wash clothes. Mouth rinsing instead of brushing teeth is required and also daily washing of the body with the prescribed chlorhexidine and alcohol. A neutropenic diet will be advised and food should always be microwaved for 10-20 seconds before consuming.
- During the isolation period supportive infusions will be given, but also a daily G-CSF injection with a dose of 5 micrograms per kg body weight (at 3 o’clock at night) to support the production of stem cells and to speed up the recovery of the neutropenic phase.
- On day 10 and day 12 the Rituximab infusions will take place.
- As soon as the blood values are sufficiently normalized and the patient is no longer ‘neutropenic’, the isolation period is lifted and the door can be opened again. Regular recovery can continue.
- Discharge date is between day 12 and day 15. Because this can not be predicted in advance, patients generally stay in the hospital at least until D+15 before returning home.
Rituximab infusions (and extra remarks concerning ATG and Ocrelizumab):
- In Russia, the HSCT protocol is concluded with 2 Rituximab infusions on day 10 and day 12.
- Because Rituximab eliminates the very last ‘corrupt’ B cells, these infusions are used to increase the effectiveness of the HSCT protocol.
- Rituximab is now a standard part of the HSCT protocols in Russia and Mexico. In the remaining countries, the older drug rATG is used instead, based on the initial protocol of Dr. Burt in Chicago. Dr. Burt obviously does not change his treatment method, because it is part of an ongoing study.
- New trials with Rituximab will not be started because the patent of this medication expired in 2015 and big profits are no longer achieved. However, a similar medicine as Rituximab has been released, namely Ocrevus (Ocrelizumab), which can be used as a ‘stand-alone’ medication, in contrast to ATG for which this is not possible.
- Ocrelizumab has become available in the Netherlands since the beginning of 2018 as a new MS DMD. Unlike other countries, Rituximab has never been available in the Netherlands (at least not covered by health insurance and therefore not available as prescription). Ocrelizumab has been released, but unfortunately the pricing is a couple of times more expensive compared to Rituximab. For Dutch politics, the availability of Ocrelizumab (and the availability of Lemtrada) seems to be an excuse to hold off the availability of HSCT in the Netherlands. If you investigate how an HSCT treatment works, it is not correct to assume that HSCT is not needed in the Netherlands. Rituximab / Ocrelizumab is a MS DMD (disease modifying drug) and only a fraction of the HSCT treatment. DMD’s can be considered to slow down the MS process while HSCT can be considered to stop the process of MS.
Evolution of the HSCT protocols (fine-tuning):
The HSCT protocols have evolved over the years and have been adjusted and improved, based on the global results in the context of risk versus effectiveness. For example, in most locations the treatment is no longer “myeloablative” but “non-myeloablative” which has to do with the intensity of the chemotherapy. The non-myeloablative variant has proven to be just as effective but more tolerable (depending on the type of patient, of course).
And also the part of Rituximab versus ATG. The HSCT treatments initially had an ATG component, but in the meantime Russia and Mexico have switched to the equally effective Rituximab in recent years. The importance of such evolutions is to maintain the outcome of the efficacy and at the same time make the treatment safer with fewer side effects.
In short, for both anti-lymphocyte antibody medicines can be chosen because they are only an “add-on” medicine to further increase the effectiveness of the treatment, but they are not the most important element behind the treatment, namely chemotherapy. Both approaches (ATG or Rituximab) seem to work equally well in terms of HSCT clinical outcome. But if everything is the same, it might be more convenient to opt for safer treatment.
Version: August 2018