In a prose to seduce the weary palate, the British neurologist, I recollect saying: “What should be the aims of HSCT treatment? At worst, remission. At best, a cure“.
I may just have to eat my words…
In a small study from Uppsala University (n=45), Larsson et al. report the effects of HSCT on neuronal damage (using neurofilament levels) and inflammation (IgG index and oligoclonal bands (OCBs)). The latter is very important as the presence of antibodies in the CNS space is a good refection of the underlying disease process. In fact >95% of those with MS are OCB positive; the remaining probably don’t have the disease or the lab technique/interpretation was poor.
I remember during my PhD re-evaluating the oligoclonal band status of a group of individuals with SPMS ~15-20y after diagnosis (many of whom have never received treatment), and to my surprise all were OCB positive.
It therefore goes without saying that OCB status in MS is very important, and furthermore ridding the body of OCBs, even more so.
So, what is the effect of HSCT on OCB status?
At >1500 day follow-up (~49 months or 4 years), in the 45 participants studied, 98% were OCB positive prior to HSCT. However, 74% remained positive afterwards (see Figure 1 below). Whilst, the proportion of those with normal IgG index (a quantitative measure of antibody production in the CSF) increased from 30% to 54%.
In my opinion, this rate of elimination of the underlying autoimmunity is insufficient to declare HSCT a success, in so far as a cure is concerned.
In a recent publication by Rejdak et al. sub-cutaneous cladribine achieved OCB negativity in 55% of PwMS at 10 year follow-up.
On the other hand, with regards to the proportion of those with elevated neurofilament levels in their CSF before HSCT (=72%), at the latest follow-up only 24% had levels exceeding the upper-limit of normal (see Figure 1 below). This indicates that HSCT has a greater chance of achieving long-term remission in selected individuals, than a cure.
My earlier enthusiasm towards HSCT somewhat deflated, I am in other ways strangely buoyed by the knowledge that clinicians are now starting to ask the right questions about treatment efficacy in MS. I eagerly await further data on HSCT and its comparative treatments.
I would also like to take this opportunity to thank all those who participated in this study, your contribution has been invaluable.
Mult Scler. 2019 Jul 26:1352458519863983. doi: 10.1177/1352458519863983. [Epub ahead of print]
Intrathecal immunoglobulins and neurofilament light after autologous haematopoietic stem cell transplantation for multiple sclerosis.
Oligoclonal bands (OCB) are widely believed to be stable over time and rarely affected by disease-modifying treatment in MS. It is presently unknown how intrathecal immunoglobulin production and other cerebrospinal fluid (CSF) biomarkers are impacted by a highly efficacious procedure such as autologous haematopoietic stem cell transplantation (aHSCT).
To describe the evolution of intrathecal immunoglobulin and neurofilament light (NFL) over time in MS patients treated with aHSCT.
In this retrospective study, available data from previously made CSF investigations in 46 patients treated with aHSCT were analysed.
After a median follow-up time of 745 days, immunoglobulin G (IgG) OCB remained detectable in 74% of patients, the proportion of patients with a pathological IgG index went down from 70% to 46%, and the proportion of patients with a pathological NFL went down from 72% to 24%. In patients with follow-up time >1500 days, IgG OCB were detectable in 50% of patients, 14% had a pathological IgG index and none a pathological NFL.
Intrathecal immunoglobulin production and NFL were lower after treatment with aHSCT, decreased over time and were normalised in a significant portion of patients. This challenges the notion that OCB are unaffected by therapeutic intervention in MS.