ClinicSpeak: why my MS clinics are running late

When will interest in HSCT as a treatment for MS subside? #ClinicSpeak #MSBlog 

“I my clinic ran very late yesterday as I had to spend a lot of time discussing HSCT with several patients. Interestingly all these patients had early progressive MS and were realising that the DMT they were on was not doing the trick in that they were clearly getting worse. This is when pwMS look elsewhere and HSCT is one of the treatments out their with a lot of 'evangelists' singing its praises. I say evangelists because we still don't have a well-defined risk:benefit ratio with which to compare HSCT with our other high efficacy therapies. Unfortunately, both grant applications that we submitted to the NIHR for funding earlier this year were rejected. The NIHR wants the UK MS Community to come together and to submit only one application."


"It is clear from our blog analytics (page views and comments) that HSCT (hematopoietic stem cell transplant) is a hot topic at the moment. The BBC Panorama programme earlier this year on this topic has a lot to answer for. It is interesting to note that as far as Google Trends go interest in HSCT appears to be quite country specific; notably the British are searching frequently using the search terms 'HSCT' and 'multiple sclerosis'"




“HSCT is simply bone marrow transplantation or BMT rebranded. There is nothing magic about HSCT; HSCT simply speeds up bone marrow recovery post-immunoablation.  There are different intensities of immunoablation. So called myeloablative therapy is aimed at wiping out your immune system completely and replacing it with a new immune system. Non-myeloablative therapy is less intense in that it simply depletes your immune system partially and allows it be rebooted (partially). The non-myeloablative therapy is clearly less risky than the myeloablative therapy, but less effective. In other words more pwMS have recurrence of their disease activity after non-myeloablative HSCT, when compared to ablative-HSCT (A-HSCT)."

"The treatment in the BBC programme was non-myeloablative HSCT (NM-HSCT). This is why the treated MSers didn’t look too bad. The chemotherapy that is used for NM-HSCT is less toxic. Many in the field believe that if you are going to treat MS with HSCT you need to go the more aggressive route and use the more toxic and risky A-HSCT. They argue that NM-HSCT is not really better than the current high-efficacy drugs we are currently using to manage MS, i.e. alemtuzumab and/or natalizumab and/or ocrelizumab (still to be launched). One of the NIHR grants was to compare NM-HSCT with A-HASCT and the other NM-HSCT with the best high-efficacy DMTs as defined by the investigators (Nz/Alemz/Ocrz)."

“Please note the chances of dying from the NM-HSCT is in the order of 0.5%-2%; i.e. 1-in-200 to a 1-in-50. In addition there is the toxicity associated with the chemotherapy; nausea, vomiting, diarrhea, hair loss, bleeding, infections, infertility and neurotoxicity to name a few. The more disabled your are the worse the neurotoxicity. If you have lost a lot of nerve fibres already and have reduced brain reserve you handle chemotherapy poorly. The chemotherapy worsens neurological function. This is why a large number of BMT units have stopped treating people with progressive MS."

“The seemingly miracle treatment effects of people in a wheelchairs getting up and walking is not unique to HSCT; we see this commonly with other highly-effective DMTs. Provided you have sufficient reserve capacity in the brain and spinal cord you will see spontaneous recovery from relapse-related disability once inflammation is switched off and recovery mechanisms are allowed to proceed. Anecdotes of Lazarus-like treatment effects has created unrealistic expectations for pwMS with more advanced disease. Please note that once you have fixed or progressive disability it is likely that you have lost much of your neurological reserve and hence even if you switch off inflammation with HSCT, or any other anti-inflammatory DMT for that matter, it is unlikely that there will be a major recovery of function. This is one reason why progressive MS trials have failed in the past. Therefore the benefit:risk ratio of HSCT changes with more advanced disease and its the reason why most HSTC trials are going to have age and disability cut-offs. This will need to be done to maximise the chances of getting a positive result.”

“So would I refer pwMS for HSCT? No, not as part of routine clinical practice. I would however be prepared to refer my patients to participate in a well-designed clinical trial to compare current treatments with HSCT. As part of the trial I would not expect my patients to pay for their treatment. The situation where HSCT is indicated as part of routine clinical care is the rare patient with MS with malignant, or very aggressive, MS that has failed all licensed treatment options. In this patient the benefits of HSCT out way the risks of the disease.”


CoI: multiple

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