Wednesday, 19 July 2017

Neutrophil loss after alemtuzumab

Gait├ín MI, Ysrraelit MC, Correale J. Neutropenia in Patients With Multiple Sclerosis Treated With Alemtuzumab. JAMA Neurol. 2017 Jul 17. doi: 10.1001/jamaneurol.2017.1456


We all know that alemtuzumab depletes lymphocytes and if you don’t, you should have read our recent papers. 

Both cladribine and alemtuzumab may effect MS via B-cell depletion.Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Neurol Neuroimmunol Neuroinflamm. 2017 Jun 5;4(4):e360.


Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab.Baker D, Herrod SS, Alvarez-Gonzalez C, Giovannoni G, Schmierer K. JAMA Neurol. 2017 Jun 12. doi: 10.1001/jamaneurol.2017.0676. [Epub ahead of print]

However, CD52 is expressed on a number of other cells like monocytes, which get transiently depleted. It is also found on sperm. 

It is also expressed on by polymorphonuclear cells. These form about 70% of your white blood cells. These are part of your first line of defense from infection. This is the main reason why you are taken out of circulation for 20-30 days after HSCT, as you have to wait for your neutrophils to be repopulated. They only live for about 5 days and then die to be replaced by new ones.

This report talks about polymorphonuclear neutrophils and says to their surprise that alemtuzumab causes loss of neutrophils in some people with MS and this hasn’t been reported before. 

Smith A, Couvillion R, Zhang R, Killackey M, Buell J, Lee B, Saggi BH, Paramesh AS.Incidence and management of leukopenia/neutropenia in 233 kidney transplant patients following single dose alemtuzumab induction. Transplant Proc. 2014 Dec;46(10):3400-4.

In MS maybe not but anyway, they report on two cases of people with MS that have severely depleted their neutrophils. This is means the people were susceptible to infection and in this paper they treat the neutrophil deficiency with granulocyte (neutrophils are a type of granulocyte as they have neutral granules compared to those with alkali granules in a basophil or acid granules in an eosinophil important as neutrophils) growth factor. So if this is interesting as a safety perspective…then surely it is interesting to know how common this event it is following use in MS.

So yesterday when I saw the paper, I trawled through the unpublished phase III trial alemtuzumab data set supplied by the European Medicines agency, wrote and submitted the paper for review and publication. So thanks for that.

So you and your neuros are aware, Neutrophils are not depleted to a great extent by alemtuzumab in most people, transient minor depletion is common in 20-25% of people, but about 3% of people develop severe neutropenia (loss of neutrophils) and this is transient in most people. You could check for this by monitoring your blood counts after alemtuzumab.

1 comment:

  1. Great work
    Did you have the free link for the paper on the blog?

    ReplyDelete

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