Barts-MS rose-tinted-odometer: ★ (milk chocolate; bitter-sweet and addictive)
I often refer to MS as being a pink-ribbon disease as close to 70% of pwMS are women.
The rising sex ratio from approximately 1:1 at the turn of the last century to almost 3:1 in most high MS incidence countries and to close to 5:1 in some areas of the world where the MS epidemic is still raging, justifies the pink-ribbon label. Explaining the rising female-to-male sex ratio really challenges those of us who think about MS and causation theory. If EBV is the cause of MS how does the EBV hypothesis explain the changing sex ratio? If you have any explanations or theories to explain the changing MS sex ratio I would be very very keen to hear them.
AHSCT or autologous haematopoietic stem cell transplantation has been getting quite a lot of air time recently. It is because it is such an effective treatment with the majority of people treated becoming NEDA, i.e. having no evident MS disease activity, and having the rate of their brain volume loss ‘normalised’ to be within the range of what you expect as a result of normal ageing. I am beginning to refer to this as NEO-EOD (no evident ongoing end-organ damage).
The problem with AHSCT is its safety profile and its associated adverse events (AEs). Despite the enthusiasm for AHSCT treatment from its very vocal supporters, the associated serious AEs are not trivial. The one AE that is the most troubling and often results in female patients saying no to a referral for AHSCT is the infertility risk. The chemotherapy used to mobilise haematopoietic stem cells and to ablate the immune system is toxic to the gonads. Men can easily bank sperm, but for women, the procedure of egg harvesting and egg banking is not trivial and it is expensive. In addition, many healthcare providers don’t cover the costs of banking; even in the UK, the latter is an NHS post-code lottery with some CCGs paying where others don’t.
Therefore, some pwMS simply take their chances with fertility. I am aware that the London haematologist that sees most of our patients quotes a figure of 40-45% for the rate of premature ovarian failure post-AHSCT. I think this figure is based on all non-cancer patients and is not necessarily specific to pwMS. Therefore it is reassuring to see the study from Italy below showing the rate to 30%, i.e. 70% of women with MS who are treated with AHSCT recover their menses. I suspect this is only half the story because the women who start to menstruate again may still be at risk of POF (premature ovarian failure) because the chemotherapy will have reduced their ovarian reserve, by culling a proportion of the ovaries oocytes or eggs. So this figure of 30% will increase with time and may end up being 45% or higher.
So it is not just about expanding access to AHSCT that is the issue but managing the AEs such as infertility that complicate the wide adoption of AHSCT for the treatment of MS. This is why I find patients tend to choose alemtuzumab over AHSCT when all of the pros and cons are presented side-by-side. So when you frame MS treatments with AHSCT as being the most effective treatment on the right people often move to the left and choose a treatment that may be less effective, but safer and unlikely to affect their fertility.
Please note I say alemtuzumab may be less effective, but I could easily say as effective, as AHSCT. Until we compare these treatments head-2-head we won’t know which is more effective. What I can say is that alemtuzumab and AHSCT are the most effective DMTs at rendering pwMS NEO-EOD.
Massarotti et al. Menstrual cycle resumption and female fertility after autologous hematopoietic stem cell transplantation for multiple sclerosis. Mult Scler. 2021 Mar 12;13524585211000616.
Data on fertility after autologous hematopoietic stem cell transplantation (aHSCT) in women with multiple sclerosis (MS) are inconclusive. This study aims to report on post-aHSCT menstrual resumption in a multi-center MS-women cohort. Out of 43 women, 30 (70%) recovered menses after a mean time of 6.8 months. Older age (odds ratio (OR) = 0.5, p < 0.0001) and previous pulsed cyclophosphamide (OR = 0.44, p = 0.005) were independently associated with a reduced menstrual recovery probability. Conditioning regimens’ intensity resulted not associated with post-procedure amenorrhea. Our results highlight younger age as significantly associated with menses recovery; proper fertility counseling for MS women candidates to aHSCT both prior- and post-transplantation is therefore warranted.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.