This is another case report about disease activation within a few months of alemtuzumab. This person was doing very well on natalizumab but stopped to have a baby.
Post-partum the person had a relapse and decided to switch to alemtuzumab.
They had a substantial relapse 4 months after dosing and there were only 0.8 lymphocytes x 10*9 /L in the blood.
There were 0.18 x 10*9 CD19+ B/L and 0.14 x 10*9 CD3 T cells in the blood.
In the CSF, CD19+ were 12% of the lymphocytes of which 40% where CD20- so they were most likely plasmablasts (plasma cells would be CD20-, and largely CD19-), there were extra oligioclonal bands in the CSF.
The inference was that the problem was B cell dysfunction.
Does this tell us the problem is in the plasmablasts and memory are not the problem?
It is cases like this that can teach us stuff. It is open access so you can all read and we need to try explain them whether it is a problem of T or B or both.
Antibody in the blood was not the problem as removal of antibody made no effect.
However, this would not remove antibodies being produced in the CSF, so maybe those in the brain were the problem.
There was no EBV detected.
Is this an issue. Only if you think they are the cause of the problem?
Maybe the relapse was destined before the alemtuzumab was started.
However, the questions are what were the other 0.4 x 10*9 lymphocytes that were not CD19+ T cells and CD3+ T cells?
Also in the CSF what were the 60% CD19 B cells that were CD20+.
Were they plasmablasts but these would be CD38+ as would mature and immature B cells so there is about 60%% CD38-ve, CD20+, CD19- . Probably would be memory B cells. But we dont know.
Remember they can become plasma blasts.
So the idea is not quite dead yet.
This person was destined for HSCT. and probably myoablative (replace the immunsystem) at that.
If you don’t do myoablative HSCT it may not be that good.
Nothing quite like HSCT to get the comments flooding in.
However, I will be tucking into my Christmas Pud rather than answering the comments I’m afraid.
The study below, suggests that relapses after 7 months can occur with non-ablative HSCT. So this appears no better than using DMT.
This also shows that HSCT is not immune to the risk of PML.
The high intensity treatment failed after ten years.
There is no question that HSCT can be very effective.
Frau J, Carai M, Coghe G, Fenu G, Lorefice L, La Nasa G, Mamusa E, Vacca A, Marrosu MG, Cocco E.Long-term follow-up more than 10 years after HSCT: a monocentric experience. J Neurol. 2017. doi: 10.1007/s00415-017-8718-2. [Epub ahead of print]
BACKGROUND:Autologous hematopoietic stem cell transplantation (aHSCT) is used in aggressive relapsing and progressive multiple sclerosis (MS). The multicentre studies and case series reported have relatively short follow-up.
AIM:To evaluate long-term effect and safety of HSCT in MS.
MATERIALS AND METHODS: Patients referred to the MS centre of Cagliari and undergoing HSCT were included. Variations in relapses and EDSS before and after HSCT were evaluated by Wilcoxon test. A descriptive analysis was made for other clinical data.
RESULTS:Nine patients (female 6, males 3; 5 relapsing-remitting, 2 secondary progressive, 1 primary progressive, and 1 progressive relapsing) performed HSCT (1999-2006). The median follow-up was 11 years (11-18). Eight patients underwent aHSCT, seven using a low intensity conditioning regimen, and one an intermediate intensity. The primary progressive underwent allogeneic HSCT, due to onco haematological disease. The relapses number decreased in the 2 years following the procedure compared to the two preceding years (p = 0.041). New relapses or disease progressions were observed after a range of 7 (low intensity regimen)-118 (intermediate intensity) months. At last follow-up, the EDSS was stable in two patients, improved in two, and worse in five (maximum 2 EDSS in one patient). Six patients showed new lesions, and seven gadolinium-enhancing on brain MRI after a mean of 23.3 and 19.8 months, respectively. Two serious adverse events were reported: melanoma, and progressive multifocal leukoencephalopathy.
CONCLUSIONS AND DISCUSSION: Our results confirm in a long follow-up the efficacy of HSCT in reducing relapses and disability progression. The risk/benefit profile is better for intermediate intensity regimens.