A patient with rapidly-evolving severe MS is having doubts about the decision to be treated with cladribine. Should she abort the cladribine and have AHSCT?
I just found out the Mexican HSCT centres have changed their protocols and are now using a standard dose of cyclophosphamide. So the reference above to HSCT-light probably does not apply to their treatment protocol anymore.
I hope you don,t mind my message I wasn't sure how to contact you. I was diagnosed in 2008my consultant advised me that has I had no obvious symptoms no treatment was required ( he informed me of the difficulty in getting treatment unless you were showing symptoms)In 2014 I was informed by my Nurse over the telephone I had progressed to SPMS I was put on Ocrevus in 2018 my mobility is the biggest problem I cannot walk unaided and as I am aware Ocrevus does not cure just slows things down. I however am progressing. I have now been told I can transfer to Ofemtumumab if I would like been reading up on this has a very similar write up to Ocrevus the only benefit would be the injection would be administered at home which would be easier as I have a 43 year old disabled daughter (I am 62) my MRI is stable but I have had no obvious side effects from Ocrevus and no obvious benefits I am finding it extremely difficult to decide do you know anything about Ofemtumumab
There is little difference in terms of the peripheral effects of ofatumumab and ocrelizumab in relation to B-cell levels. At 61 years of age the risks associated with anti-CD20 therapy increase with time. I would suggest considering an agent that is not associated with long-term immunosuppression, but has CNS penetration to target resident CNS B-cells and plasma cells.
Thank you so very much for your prompt reply I only wish I were closer so could benefit from speaking to you privately regarding my treatment but I live in South Wales and with what,s happening now it would make things even more difficult Could I ask what agents you would suggest
Dear sir, I'm wondering why you suggest Alemtuzumab over HSCT in her case. As I understand, alemtuzumab is more selective and less cytotoxic for the brain (please correct me if I'm wrong), but carries its own risks like chances of developing secondary autoimmunity. Also, wouldn't HSCT be better if she were to plan getting COVID vaccine as her immune system would recover sooner due to stem cell administration and with Alemtuzumab, or even cladribine, she would have to wait till her immune cells repopulate naturally?
It looks as if you can have the vaccine at any time in the cladribine cycle and will make an immune response. The level of immunosuppression is greater with HSCT than alemtuzumab; I am not sure you reconstitute your immune system any quicker post-HSCT. The stem cells are more about bone marrow function than T-lymphocyte function. I have a few patients with persistent lymphopaenia post-HSCT, albeit mild.
Cyclophosphamide is probably an order of magnitude more toxic than alemtuzumab, which is another reason for going with the licensed treatment.
She is not eligible for HSCT in our centre; most units don't use it first-line. The mortality rate is lower with alemtuzumab than HSCT. Secondary autoimmunity is also a problem with HSCT, with an incidence rate at about a third of that of HSCT. She has also already started cladribine; in general, it is not a good idea to abort a therapy before you have given it time to work.
Thank you for your reply sir. The reason for secondary autoimmunity in case of alemtuzumab is thought to be due to b cells repopulating in the absence of T cells. So, doesn't this risk get mitigated in HSCT due to spontaneous administration of stem cells post immune ablation?
An interesting read, though i feel for the patient who's situation is not dissimilar to my own. A question on the HSCT-light description. HSCT forums claim that the dose of cyclophosphamide is the same in Russia and Mexico as it is in the UK and it is the ATG / Rituxumab protocol which separates the approaches. Is this incorrect?
I am not sure as the protocols change all the time and this is not my area of expertise. However, one of my patients was given quite a low dose of cyclophosphamide in Mexico, in fact about a third of the dose that is used in the London HSCT centres.
To add she has to have rituximab for a further two years on returning to London. I suspect the treatment effect was due to the rituximab or at least it was a major component of the protocol.
I just found out the Mexican HSCT centres have changed their protocols and are now using a standard dose of cyclophosphamide. So the reference above to HSCT-light probably does not apply to their treatment protocol anymore.
I hope you don,t mind my message I wasn't sure how to contact you. I was diagnosed in 2008my consultant advised me that has I had no obvious symptoms no treatment was required ( he informed me of the difficulty in getting treatment unless you were showing symptoms)In 2014 I was informed by my Nurse over the telephone I had progressed to SPMS I was put on Ocrevus in 2018 my mobility is the biggest problem I cannot walk unaided and as I am aware Ocrevus does not cure just slows things down. I however am progressing. I have now been told I can transfer to Ofemtumumab if I would like been reading up on this has a very similar write up to Ocrevus the only benefit would be the injection would be administered at home which would be easier as I have a 43 year old disabled daughter (I am 62) my MRI is stable but I have had no obvious side effects from Ocrevus and no obvious benefits I am finding it extremely difficult to decide do you know anything about Ofemtumumab
There is little difference in terms of the peripheral effects of ofatumumab and ocrelizumab in relation to B-cell levels. At 61 years of age the risks associated with anti-CD20 therapy increase with time. I would suggest considering an agent that is not associated with long-term immunosuppression, but has CNS penetration to target resident CNS B-cells and plasma cells.
Thank you so very much for your prompt reply I only wish I were closer so could benefit from speaking to you privately regarding my treatment but I live in South Wales and with what,s happening now it would make things even more difficult Could I ask what agents you would suggest
Dear sir, I'm wondering why you suggest Alemtuzumab over HSCT in her case. As I understand, alemtuzumab is more selective and less cytotoxic for the brain (please correct me if I'm wrong), but carries its own risks like chances of developing secondary autoimmunity. Also, wouldn't HSCT be better if she were to plan getting COVID vaccine as her immune system would recover sooner due to stem cell administration and with Alemtuzumab, or even cladribine, she would have to wait till her immune cells repopulate naturally?
It looks as if you can have the vaccine at any time in the cladribine cycle and will make an immune response. The level of immunosuppression is greater with HSCT than alemtuzumab; I am not sure you reconstitute your immune system any quicker post-HSCT. The stem cells are more about bone marrow function than T-lymphocyte function. I have a few patients with persistent lymphopaenia post-HSCT, albeit mild.
Cyclophosphamide is probably an order of magnitude more toxic than alemtuzumab, which is another reason for going with the licensed treatment.
She is not eligible for HSCT in our centre; most units don't use it first-line. The mortality rate is lower with alemtuzumab than HSCT. Secondary autoimmunity is also a problem with HSCT, with an incidence rate at about a third of that of HSCT. She has also already started cladribine; in general, it is not a good idea to abort a therapy before you have given it time to work.
Thank you for your reply sir. The reason for secondary autoimmunity in case of alemtuzumab is thought to be due to b cells repopulating in the absence of T cells. So, doesn't this risk get mitigated in HSCT due to spontaneous administration of stem cells post immune ablation?
An interesting read, though i feel for the patient who's situation is not dissimilar to my own. A question on the HSCT-light description. HSCT forums claim that the dose of cyclophosphamide is the same in Russia and Mexico as it is in the UK and it is the ATG / Rituxumab protocol which separates the approaches. Is this incorrect?
I am not sure as the protocols change all the time and this is not my area of expertise. However, one of my patients was given quite a low dose of cyclophosphamide in Mexico, in fact about a third of the dose that is used in the London HSCT centres.
To add she has to have rituximab for a further two years on returning to London. I suspect the treatment effect was due to the rituximab or at least it was a major component of the protocol.