Your questions

HSCT Congress Moscow, November 22-23, 2019

In less than 10 days (November 22 and 23, 2019) the important international congress on stem cell transplantation for autoimmune diseases will take place in Moscow.

Many of the top international researchers and practitioners will be present. Not only will Denis Fedorenko¹ present himself, but also Richard Burt², Joachim Burman³, Riccardo Saccardi⁴, John Snowden⁵ and many more top players in the field.

The topics that will be discussed are incredibly important for practitioners and researchers in the field, but they are also very interesting for patients considering the treatment.

I personally believe that it is very important for me to be present at this event. Not only to gather as much information as possible for Stichting MS in beeld that I can share with you. But also to personally meet these ‘top players’ in the field of HSCT for MS. I already have had contact with many of the speakers via Skype or email, but it is great to get to meet them in person and to further expand my network.

Topics to discuss

I will be attending the conference together with Ellen Kramer, Dutch HSCT expert and board member of Stichting MS in beeld.

I am collecting topics to discuss with the experts at the conference. Ellen and I will then discuss these topics and share our insights with you.

So far I have collected the following questions. If you have any additional questions, please let me know by leaving a message at “leave a comment” below, or respond to my Facebook message. Then I will make sure to include them.

Questions

1. The EBMT discourages the use of HSCT for people with MS who do not have an “active” disease⁶. In a recent blog post, BartsMS also discourages the use of HSCT for progressive MS. Yet they treat many SPMS & PPMS patients who do not meet this condition, in fee-for-service BMT units around the world. Incredible success rates are reported by these units for this group of patients, how is that possible, and why is the treatment not recommended by most experts?
2. How do you measure the success/effectiveness of an HSCT treatment in MS-patients that do not have MRI-activity or clinical relapses? In untreated patients, EDSS progresses very slowly at higher scores. Even if there would be a well-matched control group of progressive MS patients, finding a statistically significant difference between an untreated and treated group would be difficult and would likely require many years of follow-up.
   When fee-for-service BMT units report success, how is this measured, especially for progressive MS patients without clinical relapses or active MS inflammation visible on MRI?
3. Could the HSCT treatment make the MS/neurodegeneration worse? There have been some reports of chemotherapy caused acute neurotoxicity.
4. Both in Russia and in Mexico no ATG is used in their treatment protocol. The rest of the centres do this, and the EBMT also recommends its use⁷. What is the motivation for this choice and does it have a possible impact on the long-term effectiveness of the treatment?
5. Is there a reason to prefer a more intense chemo-protocol (e.g. BEAM)? A number of European centres keep using BEAM, while in new trials always a cyclophosphamide + ATG treatment is given. Some people profess to the idea that it is more effective with progressive MS to use heavier chemotherapy.
6. In the treatment protocol used in Mexico, the four days on which the chemical agent cyclophosphamide is given are split by a period of one week. Does this have a negative effect on the effectiveness of the treatment? Why is this treatment schedule only applied in Clínica Ruiz?
7. Why are there no articles published in renowned scientific journals from the A.A. Maximov centre, which has already treated more than 1000 patients? This Russian centre the world’s highest number of people with MS treated with HSCT, sharing their knowledge could help many people.
8. Opinions on how to handle vaccinations after HSCT vary considerably between centres. In general, only vaccinations with live attenuated viruses are considered a higher risk of inducing a recurrence of MS. However, some centres discourage the use of vaccines, some find it unnecessary, and others use a vaccination schedule. What is the general opinion about this? Are vaccinations necessary or bad?
9. When after HSCT treatment, a relapse occurs, what is the recommended treatment?
10. I am very interested in the long-term effectiveness of the treatment. Some studies have been started in the past, that resulted in some long-term measurements⁸ e.g. the study by Shevchenko⁹, there has been a retrospective multi-center cohort study¹⁰ and a report on a single centre’s experience¹¹. Logically, an overview of the long-term effectiveness of the more recently introduced lower-intensity regimens is lacking. Can you make an educated guess about the difference in the effectiveness of these new regimen compared to the older, higher-intensity protocols?
11. If the chances of success are really as high as those reported by Dr Fedorenko, why is this method not used worldwide for all people with MS?

Imagine that you would start a fee-for-service HSCT treatment facility for patients with MS

• What protocol would you offer (e.g. would you go for BEAM, Cy+ATG or Cy+Rituximab)?
• What would your inclusion criteria be (e.g. which patients would you treat, and which patients would you not treat)?
• Which measures of efficacy would you use to keep track of your success rate?
• Keeping in mind that most of your patients will be abroad, how would you do the follow-up and keep track of long-term effectiveness/side-effects?

Most of you know that I live in Manila nowadays, which means that it will be a long and costly journey for me. A rough estimate of the costs amounts to approximately €1500. 
I believe that this conference is very important for the work that I am doing for Stichting MS in beeld. Therefore, I will go even if it will personally cost me a lot of money.

However, if people wanted to sponsor this trip, I would be very grateful for that.

You can donate to the foundation via the ‘donate’ page. If you have a suggestion about where I can find potential donors, or if you want to contact me for another reason, you can do so by emailing me at bram@msinbeeld.nl.

Footnotes

1. chief physician of the department in Moscow 
2. amongst other things, principal investigator of the MIST study, and HSCT-expert from Chicago 
3. author of many studies on HSCT for MS, from Sweden
4. the top Italian expert on HSCT
5. amongst others, the contact-author of the updated EBMT guidelines, from the UK
6. EBMT: “aHSCT may play a role in the treatment of the progressive forms of MS. However, based on scientific insights, the authors recommend aHSCT only when a patient has had inflammation in the central nervous system in the past year. It is preferable to offer treatment with HSCT as part of a clinical study.”
7. EBMT: “Due to a lack of data on the effectiveness of other treatment regimens, the authors recommend the use of the EBMT-recommended regimen with cyclophosphamide 200 mg/kg + ATG or BEAM + ATG.”
8. See Table 1 of Autologous hematopoietic stem cell transplantation in multiple sclerosis: 20 years of experience
9. Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives
10. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis
11. Long-term follow-up more than 10 years after HSCT: a monocentric experience