The following overview will show from day to day what is planned during the aHSCT treatment in Moscow. Some things might shift here and there, but it certainly gives a good indication. The process takes 30 days. The transplant day is called “Day 0”. The days before are indicated as minus and after te transplant the days add up again.
The dates entered apply to the planned treatment of Tanja, Mama with MS. An ideal overview for those staying at home, but also a good indication for future patients. The schedule can easily be adopted from your own start date.
Under the Calendar, you can continue reading about valuable substantive information regarding the HSCT treatment process.
|~ CALENDAR ~|
|Weekday||Date||Day nr.||Program – aHSCT|
|Saturday||6 oct.||.||Travel to Moscow|
|Sunday||7 oct.||.||Day off|
|~ WEEK 1 ~|
|Monday||8 oct.||D-15||Intake / Tests|
|Tuesday||9 oct.||D-14||Testing day|
|Wednesday||10 oct.||D-13||Rest day|
|Friday||12 oct.||D-11||Mobilisation day 1: stem cell injections (G-CSF) at 23h and 3h|
+ Prednisone infusion at 10-11h
|Saturday||13 oct.||D-10||Mobilisation day 2: stem cell injections (G-CSF) at 23h and 3h|
+ Prednisone infusion at 10-11h
|Sunday||14 oct.||D-9||Mobilisation day 3: stem cell injections (G-CSF) at 23h and 3h|
+ Prednisone infusion at 10-11h
|~ WEEK 2 ~|
|Monday||15 oct.||D-8||Mobilisation day 4: stem cell injections (G-CSF) at 23h and 3h|
+ Prednisone infusion at 10-11h
+ 1st Neckline
|Tuesday||16 oct.||D-7||Harvesting of tem cells via blood dialysis (5-6 hours, 2 million per kg./b.w.)|
|Wednesday||17 oct.||D-8||Rest day (or extra harvesting day if needed)|
+ 2nd Subclavia line
|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.||Dag 0||Transplantation day|
|Wednesday||24 oct.||D+1||Rest day / Isolation|
|Thursday||25 oct.||D+2||Isolation (this period takes +/- 1-10 days, depending on the blood results).|
|~ WEEK 4 ~|
|Friday||2 nov.||D+10||Isolation + Rituximab infusion (not exact: will be between day +10 and +12)|
|~ WEEK 5 ~|
|Tuesday||6 nov.||D+14||Recovery / Discharge?|
|Wednesday||7 nov.||D+15||Recovery / Discharge|
|Thursday||8 nov.||D+16||Travel back home|
Stem cell injections & harvesting your own stem cells:
- The HSCT procedure performed in Moscow is actually an aHSCT procedure. The ‘a’ stands for autologus, which means that there will be a transplant with your own body stem cells (not from a donor, this is called allogeneic).
- In order to harvest the stem cells, firstly they need to be produced in large numbers by your own body. To achieve this, supporting stem cell injections will be given for 4 days to “mobilize” the stem cells.
- G-CSF injections will be given twice a day at 11 p.m. and at 3 p.m. 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 opens up so that the pure and newly created stem cells end up in the bloodstream. This process can cause bone pain. Other most common side effects are headache, fever and other flu-like symptoms.
- After 4 days of injections, blood dialysis will take place on the following day (via a neck catheter). In this way the body’s own stem cells can be harvested from the blood and then frozen until the transplant day.
- For a successful stem cell transplant, 2 million stem cells must be harvested per kilogram of body weight. Harvesting via the dialysis machine usually takes 5 to 6 hours. In case of insufficient stem cells on the first day, the harvesting will resume on the next scheduled rest day. In this way, nothing needs to shift in the planning above.
- Extra remark: Most patients will shave their hair before or after placing the neckline from a practical point of view. The neckline should not get wet, so washing hair will no longer be possible from that moment. Hair loss only occurs during the isolation period. Experience shows that it is more convenient and cleaner to deal with short hairs falling out, than large strands of hair in your room.
- After successful harvesting and storage of the stem cells, a (non-myelo ablative) chemo trajectory of 4 days will take place by means of administering Cyclophosphamide.
- After harvesting the stem cells, the neck line will be removed and a new “Subclavia line” will be placed on the shoulder, near the collarbone. This 2nd ‘catheter’ is a lot more comfortable and has 3 tubes at the end. As a result, patients no longer need to be punctured during treatment, but chemo and other medications can be administered as well as daily blood tests. This is very practical; less risk of infections and less damaging on blood vessels.
- In fact, chemotherapy is the most important aspect of the treatment; a ‘hard reset’ of the immune system to completely eliminate 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).
- A total of 200 mg Cyclophosphamide is administered per kilogram of body weight over 4 days. So 50 mg / kg / b.w. every day.
- Supportive infusions and medication are administered during chemo, such as anti-viral, anti-bacterial, anti-fungal and very good medication for nausea. Patients rarely vomit at this facility.
- The most common side effects are: fever, nausea, vomiting, diarrhea, constipation, hair loss, oropharyngeal mucositis (mucosal inflammation in the mouth), pancytopenia (abnormally low blood cell count), haemorrhagic cystitis (pain in the abdomen and frequent and painful urination).
Stem cell transplant:
- After resetting the immune system by means of chemotherapy and a rest day, the previously harvested stem cells will be transplanted back into the body. This day is marked 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 yet. It could occur that the administration of these stem cells will repair some of the (not yet permanently) lost functions. However, such improvements of physical functioning must be seen as a ‘bonus’ and is certainly not a guarantee. The stem cells can provide support during recovery, but the body must do it itself. Lost tissue / permanent damage cannot be reversed.
- The most common side effects are: nausea, cough, shortness of breath, vomiting, hot flashes, fever, chills, high or low blood pressure.
- After the transplant the blood values will drop drastically and at a certain moment the patient will enter the ‘neutropenic phase’ in which the white blood cells are dangerously low to totally absent. From that moment, the body no longer has an immune system. The isolation period will be necessary untill the White blood cell count is above 1 again.
- The isolation lasts on average 9 to 10 days and starts approximately on D+1 / D+3 and lasts up to approximately D+8 / D+12.
- During the isolation, the patient is no longer allowed to leave the room and the door remains closed. The suitcase and own clothing are removed (so don’t forget to keep socks and underwear in the cupboard). The medical staff will clean the room daily, change bed linen and bring a sterile set of clothes (judo suit). Brushing your teeth and showering is not permitted. Instead, you get mouthwash and 2 different bottles of alcohol to make the body sterile every day.
- A neutropenic diet will be served. 4 Meals per day and precisely tuned for a high intake of nutrients and vitamins. Hot food should always be reheated in the microwave for 10-20 seconds before consuming (extra bacterial killing).
- Each room has a fridge, microwave and kettle, so that you can enjoy your own products as well.
- During the isolation period, supportive infusions will be given as well as a daily G-CSF injection (at 3 o’clock at night) to support the production of stem cells and to speed up the recovery of the neutropenic phase.
- As soon as the blood values are sufficiently normalized (White blood cell count above 1) and there is no longer any question of neutropenia, the isolation period is canceled and the door can be opened again. From then on, “mask mode” applies whereby the patient is only allowed to leave the room with a mask i.e. to go to the social room.
- Depending on the recovery and the blood values, a Rituximab infusion will take place between days 10 and 12. The doctor calls this a “top-up”, an extra ‘clean-up action’ to remove any remaining ‘bad’ B cells, so that they cannot instruct any T cells to cause MS symptoms again.
- The discharge date is between day 12 and day 15. Since this cannot be predicted in advance, patients generally continue to recover at least until D+15 in the hospital and then return home. In the event of unexpected complications somewhere during the process, it is certainly wise to plan the departure date not earlier than one month after the start date. In short, if the start date is on, for example, the 5th of the month, it is wise to also book the return flight on the 5th of the following calendar month.
Rituximab infusion (and extra note with regard to ATG and Ocrelizumab):
- In Russia, the HSCT protocol is concluded with 1 Rituximab infusion, approximately from day 10 or later, depending on the medical condition.
- Because Rituximab eliminates the very last ‘corrupt’ B cells (should they still exist), this infusion is 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 other countries, the older drug rATG is used instead of this medication, based on the initial protocol of Dr. Burt in Chicago.
- Russia and Mexico have deliberately chosen Rituximab because the tolerance is many times better than treatment with ATG. Rituximab is less stressful for the body and the recovery period is more comfortable. In addition, rATG has a high risk of serious skin infections, among other things, which is undesirable in convalescent patients with a low immune system.
- Naturally, Dr. Burt will not change his treatment method, as it is part of an ongoing study.
- New trials with Rituximab will not be started because the patent for this drug expired in 2015, so the (financial) profits no longer apply (for the manufacturer). However, a comparable medicine such as Rituximab is now available, namely Ocrevus (Ocrelizumab), which can be used as a ‘stand-alone’ medicine, in contrast to ATG for which this is not possible. Rituximab and Ocrelizumab specifically bind to B cells. ATG does not.
- In case of very active and aggressive MS, where the MS seems to ‘flare up’ again after the HSCT treatment, it is possible to administer an additional Rituximab infusion as a so-called ‘top-up’. If Rituximab is not available in your own country, Ocrelizumab may be used as well. If all goes well, this will not be necessary. The advice on this topic needs to be tailored to the situation of the individual patient.
- Extra remark: Ocrelizumab has been available in the Netherlands since the beginning of 2018 as a new MS drug. Unlike other countries, Rituximab has never been available in the Netherlands. Ocrelizumab has become available, but as expected the price is many times higher compared to Rituximab. For Dutch politics, Ocrelizumab (and the availability of Lemtrada) seems to be an excuse to prevent the availability of HSCT in the Netherlands. When you further explore how an HSCT treatment works, it is not correct to assume that HSCT does not have to be available in the Netherlands at all. Basiclly, the choice for this treatment is taken away from the patient. Rituximab / Ocrelizumab are DMD’s which slow down progression and in this case, are only a fraction of the HSCT treatment (the chemo is the most important element). In the Netherlands, only MS drugs are offered to slow down the disease, while HSCT can be seen as an MS stopper.
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.
Latest version: January 2019