Treatment of progressive MS with aHSCT
In November 2019, I was in Moscow for the international conference on stem cell treatment for autoimmune diseases.
The first day of the congress was mainly devoted to the treatment of multiple sclerosis with chemotherapy followed by autologous hematopoietic stem cell transplantation (aHSCT). One of the main questions that concerned many patients received a lot of attention.
“Is aHSCT suitable for treating patients with progressive MS?“
During a panel discussion, scientists from around the world emphasized their position on this topic:
“From our experience, based on animal studies and clinical study results, we conclude that aHSCT is not effective for people with long-term progressive MS, for whom no active MS inflammation is visible on the MRI scan, and for whom no acute relapses occur.”
Nevertheless, the department of Prof. Dr. Denis Fedorenko, less than 100 meters away from the convention center, performs this treatment dozens of times a year for exactly this group of patients. With great success, says Prof. Fedorenko, an opinion that is firmly confirmed by the vast majority of people who underwent treatment.
When I was awake at night in my hotel room, all kinds of questions were going through my mind.
What can explain this huge difference? Do they have experience here in Moscow that is missing in other centers? Is the MRI equipment and the knowledge of the radiologists better here, and are most patients who undergo the treatment incorrectly diagnosed in their home country? Is the aHSCT treatment protocol superior here in Moscow? Are the facilities here better? Do they perhaps use more advanced equipment for taking and storing the stem cells, or is the department better equipped?
I do not doubt the extensive knowledge and experience of the well-known American HSCT-pioneer professor Richard Burt and experts such as John Snowden, Riccardo Saccardi and Joachim Burmann, who unanimously endorsed the statement above during the panel discussion. The idea that there is superior knowledge and experience in Moscow, which translates into a more effective HSCT treatment, seems out of the question to me.
Is it then the diagnostic technique that is better in Russia, as a result of which a larger group of patients actually have inflammatory activity in their central nervous system which was previously overlooked? That also does not seem to be the case. Some of the patients come from centers that are renowned for their MR-imaging. because not only is the MRI diagnostics for MS in the Netherlands renowned worldwide, but the experts in the panel largely base their opinion on data collected using the MRI techniques available to them.
Is the aHSCT treatment protocol that they use in Moscow better suited for treating people with progressive MS? That also does not seem to be the case, after the many presentations on the first day of the conference it has become clear that the protocol used here in Moscow is essentially no different from what is used in other centers and studies.
The last consideration that crossed my mind was that the hematology department of the center here in Moscow or the equipment that they use is somehow more advanced and better? But after a visit to Prof. Fedorenko’s department together with Ellen Kramer, it appears that this is also not the case. All transplantation centers in Europe must meet very strict JACIE requirements, drawn up by the EBMT, the European society for blood and bone marrow transplants. These requirements are formulated with the idea in mind that these centers often treat severely weakened and sick cancer patients. Ellen performs these JACIE accreditations for the EBMT in the Dutch language area and therefore has excellent insight into the transplantation departments.
The question that remains is, how come that the many patients who have been treated by Dr. Fedorenko experience success after their treatment.
I am convinced that neither of them would lie about this.
Perhaps the answer to this lies partly hidden in the way in which ‘success’ is experienced and quantified.
In clinical studies, on which the experts around the world base their opinions, success is often measured by the absence of a change in the EDSS score, new lesions on MRI and documented clinical relapses. In the group of progressive MS patients without detectable inflammatory activity, there are by definition no new lesions on the MRI and clinical relapses do not occur (this is part of relapsing-remitting MS). The result is that success measurements are often based on changes in the EDSS-score, a measure that has many shortcomings, and above a score of 5.5 is basically solely influenced by mobility.
Prof. Dr. Fedorenko’s clinic works with standardized questionnaires that map the degree of disability, but also the fatigue and quality of life of the patients. As the majority of patients will not travel to Russia for a follow-up examination, these questionnaires are sent to patients at home via email. This undoubtedly yields different results than when every patient would be seen by a doctor for a short EDSS assessment.
However, this cannot be the only explanation for the difference in the degree to which patients perceive success. They are talking about a life-changing event and, without exception, are extremely enthusiastic about their treatment in Russia. Even individuals, who indicate that his / her MS continued to progress despite treatment, do not regret their heavy undertaking!
Only after my visit to the department, discussions with Ellen Kramer, patients and with Dr.Fedorenko himself the secret of Russia dawned on me…
I found this an extremely difficult article to write. I know how big the influence of negative stress and uncertainty can be on a person’s well-being, especially in people with MS. It is certainly not my intention to give people with progressive MS, who have decided for an aHSCT treatment extra stress and doubt. I went on a search, and these are my thoughts. Unlike the other pieces that I write, this one is not based on science, I actually believe that exact science is not able to provide the answer.
My understanding started with the question of how a patient with progressive MS actually ended up at the center of Dr. Fedorenko.
Following the conference, I wondered how it is possible that almost all experts say very clearly: “HSCT for progressive MS: DON’T DO IT!”, while Dr. Fedorenko and practically all treated patients contradict this loudly (and I really don’t believe they are lying).
People with progressive MS are increasingly losing their roles in society. Many have lost their jobs, become more and more disabled, marriages are disrupted or broken and friends disappear. Then there are also neurologists who say that you no longer need to see them ‘because he/she can no longer do anything for you’. Medications that work well for patients with RRMS do not work, and treatments to reduce symptoms are often not considered by neurologists.
People in this situation literally indicate that they feel abandoned and alone.
And then…. a quick internet search leads to HSCT-Russia.com, after one click on the ‘contact’ button you receive an extremely friendly response from Anastasia by return mail. You are welcome! Anastasia herself is the best advertisement for the department: she herself is an ‘ex-MS patient’ who has been treated by Dr. Fedorenko and now confidently strides through Moscow with a glitter dress and stilettos. Fedorenko calls you his friend and guarantees that he can help you.
The next step is to raise the money for the treatment. Your family, friends, and acquaintances come into action and go crowdfunding. You get plenty of attention, you matter and are once again part of society. You feel that there are loads of people that love you.
Patients are super busy: a visa has to be arranged, flights and a hotel have to be booked. Legal matters must be arranged, aftercare upon return to their home country must be considered and, in addition, goodbyes for a month have to be said to family and friends. Without a doubt, the thought wanders through your mind that this goodbye, in an unfortunate turn of events, might be forever.
I myself also had to arrange a lot to be able to attend the congress and visit the hospital. I also had to apply for a visa and arranging a ‘letter of invitation’ and an international health insurance. After arrival, I was picked up from the airport by driver Constantine, who was arranged by Anastasia. He barely spoke English and constantly called, sometimes even with two phones at the same time, forcing him to steer with his elbows. From the window I saw large apartment buildings and factories with names written in an alphabet that I could not decipher.
Patients who come to this hospital for treatment receive some tests during the first few days, a subclavian catheter is placed, and an MRI-scan is made. Eventually a conversation with the head physician, Dr. Fedorenko follows. If you still have any doubts about the treatment or the department, it will disappear like snow in the sun after the conversation with the frank, concerned and friendly doctor.
During my visit to the department, he told me that for people with inactive progressive MS, the treatment goal is to halt the progression of their MS. This is only partly achieved by the HSCT treatment according to the doctor, there is another essential component.
Dr. Fedorenko is investing heavily in group feeling. Patients are brought together. Emotional moments are experienced together. In the event of hair loss, a head-shaving party is organized where everyone can be present. The re-infusion of the stem cells is a huge event that has to be celebrated: the rebirthing party. Dr. Fedorenko speaks the words that “the beast is now conquered”. He pours liquid nitrogen over the ground: the rebirthing confetti.
Immediately at the start of the treatment, Dr. Fedorenko also focused on healthy eating, quitting smoking, and exercising. It is known that lifestyle has a major influence on the disease. Patients are encouraged to walk without a walking aid and to go outside as quickly as possible. Loads of steroids are given during treatment, these are essential to prevent MS activity during treatment, but at the same time these steroids promote the conduction speed of nerve cells, making most patients feel better quickly; the feeling that the ‘beast has been conquered’ is strengthened by this.
Dr. Fedorenko has his office in the department, works long days, has a lot of contact with the people, celebrates the parties, makes time available for the people and is often there on weekends too. He knows all kinds of personal details and shows that to the patient and family. He encourages people to take on a new age (the day that the stem cells are reinfused is their new birthdate) and makes them a member of the “New Life Association”. They then get a blue iris: the symbol he uses for that. The contact with Anastasia is also very intensive and nothing else than extremely positive.
A bond is formed with the other patients. Families are all sitting together in a hotel and have intensive contact with each other: eating together, taking a bus or a taxi together, etc. Once back in their home-countries these contacts often remain and patients continue to support each other.
During the entire procedure and far beyond, the patient receives a great deal of attention from their family, but also from people who have donated money. Everyone wants to know how you are doing.
Progressive MS patients have nothing to lose and what they win is attention from family, a doctor who listens to them and support from their entire network. And just maybe you are just the one who benefits from the treatment and stops progression. Furthermore, patients also state that their quality of life is so poor at the moment due to MS that they are happy to accept the 0.3% mortality risk. After the treatment, everyone unanimously agrees that he/she is happy to have taken this step. Patients have the feeling that they have ‘done something’.
Patients that are treated by Dr. Fedorenko are encouraged to change their lifestyle and their comorbidities are treated. In addition, the positive effect of attention, love, and the fact that you have endured all the hardships of the long journey and the heavy treatment, should not be underestimated.
The visit to Moscow and the department of Dr. Fedorenko was particularly insightful and enlightening. Although experts worldwide have a clear position when it comes to aHSCT treatment in people with inactive progressive MS, the many success-experiences after treatment can’t be measured by exact science. It appears that for now, we have to be content with the above-unraveled ‘secret’ of Russia.