Effectiveness of aHSCT in MS

Experts agree that there is more than sufficient evidence for the use of aHSCT in the treatment of aggressive MS. For forms of MS with an active inflammatory component, the choice of aHSCT remains a consideration. For MS without inflammation, the use of aHSCT is discouraged by almost all experts.

During the conference in Moscow on November 22, there was hardly any discussion about the treatment of aggressive MS using aHSCT. Not because this wasn’t interesting, but because it is so obvious that the effectiveness of an aHSCT treatment for this small group of patients far outweighs the risks that this treatment entails. All experts present agreed that in the case of active RRMS that is rapidly deteriorating, despite the use of a regular drug, aHSCT treatment should be considered.

Multiple studies show that the use of aHSCT is effective in the treatment of active RRMS. It is preferable that the decision for aHSCT treatment is taken by a well-informed, ideally multidisciplinary, team of experts. In many cases, treatment with a regular, approved, drug may be preferred.

There are still many open questions about the treatment of SPMS with active inflammation (the transition phase between RR and SPMS). In this case, it is very important to select the right patients who can benefit from the aHSCT treatment while at the same time having an acceptable risk of complications. The conclusion is that further research needs to be done on this and the current advice is that all SPMS patients should only be treated with aHSCT in the context of a clinical study.

For progressive MS without active inflammation (SP or PPMS without visible inflammation on MRI or clinical relapses), treatment is discouraged. Although no scientific studies have been done for this, almost all experts worldwide share this view based on clinical experiences, descriptive studies and animal testing. Some experts even warn that the treatment can speed up the breakdown of nerve cells.

PPMS with active inflammation was only briefly discussed, no studies have been done yet. It was speculated by some that aHSCT treatment might be beneficial for this group of patients, but no conclusions can be drawn from this due to the lack of data and experience. This is why treatment for all PPMS patients is currently discouraged by almost all experts (unless this happens in connection with a clinical study).

The message is: there is sufficient evidence for the effectiveness of aHSCT in the treatment of aggressive MS and (despite the use of medication) highly active RRMS. From smaller and non-randomized studies, it appears that aHSCT can be considered for patients with MS with active inflammation visible on an MRI scan or with periods of clinical relapse. However, for most patients, regular, approved, drugs can be sufficiently effective and the higher risk of HSCT treatment is not justified. 
Treatment is not recommended for progressive MS without active inflammation. No scientific studies have been done for this, but on the basis of clinical experiences, descriptive studies and animal testing this opinion is shared by almost all the experts worldwide. 
Some experts warn that the chemotherapy used in aHSCT can speed up the degeneration of nerve cells.

The treatment appears to be most effective for younger patients with a shorter disease duration, a lower EDSS score, RRMS, active inflammation and no additional diseases.

Based on these insights and the previously discussed article with guidelines from the EBMT, I have made the following illustration of the effectiveness of aHSCT in MS.

Aggressive RRMS: a group of 4-14% of MS patients with an accelerated (3-4 times faster) disease course 
Active RRMS: MS with a relapsing-remitting course, with new MRI lesions or clinical relapses 
Active SPMS / PPMS: MS with a progressive course, with new lesions on MRI or clinical relapses 
Inactive SPMS / PPMS: progressive MS with no new MRI lesions or clinical relapses with the system

From the source article we can read the detailed descriptions of the terms used:

Grade I: Evidence from at least one well-executed randomised trial
Grade II: Evidence from at least one well-designed clinical trial without randomisation; cohort or case-controlled analytic studies (preferably from
more than one centre); multiple time-series studies; or dramatic results from uncontrolled experiments 
Grade III: Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports from expert committees

Standard of care (S): Indications categorised as S are reasonably well defined and results compare favourably (or are superior) to those of nontransplant treatment approaches. Obviously, defining an indication as the standard of care does not mean an HSCT is necessarily the optimal therapy for a given patient in all clinical circumstances. “Standard of care” transplants may be performed in a specialist centre with experience in HSCT and an appropriate infrastructure as defined by the JACIE guidelines

Clinical option (CO): The CO category applies to indications for which the results of small patient cohorts show efficacy and acceptable toxicity of the HSCT procedure, but confirmatory randomised studies are missing, often as a result of low patient numbers. The broad range of available transplant techniques combined with the variation of patient factors such as age and co-morbidity makes interpretation of these data difficult. Our current interpretation of existing data for indications placed in this category supports that HSCT is a valuable option for individual patients after careful discussions of risks and benefits with the patient but that for groups of patients the value of HSCT needs further evaluation. Transplants for indications under this heading should be performed in a specialist centre with major experience in HSCT with an appropriate infrastructure as defined by JACIE guidelines

Developmental (D): Indications have been classified as D when the experience is limited, and additional research is needed to define the role of HSCT. These transplants should be done within the framework of a clinical protocol, normally undertaken by transplant units with acknowledged expertise in the management of that particular disease or that type of HSCT. Protocols for D transplants will have been approved by local research ethics committees and must comply with current international standards. Rare indications where formal clinical trials are not possible should be performed within the framework of a structured registry analysis, ideally an EBMT non-interventional/observational study. Centres performing transplants under this category should meet JACIE standards

Generally not recommended (GNR): The GNR category comprises a variety of clinical scenarios in which the use of HSCT cannot be recommended to provide a clinical benefit to the patient, including early disease stages when results of conventional treatment do not normally justify the additional risk of aHSCT, very advanced forms of a disease in which the chance of success is so small that does not justify the risks for patient and donor, and indications in which the transplant modality may not be adequate for the characteristics of the disease. A categorisation as GNR does not exclude that centres with particular expertise on a certain disease can investigate HSCT in these situations. Therefore, there is some overlap between GNR and D categories, and further research might be warranted within prospective clinical studies for some of these indications