How Do Stem Cell Transplants Work to Treat Myelofibrosis?

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Topics include: Treatment and Understanding

During this Ask the Expert segment, Patient Power community member Robert writes in, “How does a stem cell transplant cure myelofibrosis?” Myeloproliferative neoplasm (MPN) expert Dr. Joseph Scandura, from Weill Cornell Medicine, responds by explaining the affect a transplant has on MPN cells and potential treatment side effects. Dr. Scandura also shares progress with the innovative immunotherapy, CAR-T cell therapy, and its’ efficacy with MPN patients. Watch now to find out more.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

So, Robert wrote in and said, “How does a stem cell transplant cure myelofibrosis?”

Dr. Scandura:              

So, I’ll go back to that factory analogy. If you think of the bone marrow as being sort of corrupted by these MPN cells. You have, normally this is a very orderly factory. It’s producing a number of different lines if you think of it as a car factory. You can be producing red blood cells maybe your sportscars, and your white blood cells, your infection-fightingcells, as sedans, and platelets as SUVs, but it’s all very orderly and it should be proceeding in a regular way. And you get MPNs and somebody has just turned up the volume and are just cranking out a lot of cells. And sometimes that production starts becoming abnormal too and that’s more like in a myelofibrotic setting. 

And so, what is the point of a stem cell transplant is really to clear out that factory, get rid of all the workers in there, and replace them with completely different workers to come in, set up shop, clean up the factory, and start normal blood cell production. There’s another part of it is, it’s not just the blood cells, it’s actually the immune system. And so, you’re giving the recipient an entirely new immune system. You have to wipe out the old immune system to allow the new donor cells to get a hold in the bone marrow and then they have to be educated to sort of relearn how to fight off infections and to figure out who is who. 

 

So, graft versus host is one of the complications where those cells from another person come into the recipient and say, “Ah, I don’t know you. I’m going to attack.” And so, that can be a problem. It can be a short-termproblem. It can be a long-termproblem. It can be mild and it can be severe, but there’s another edge of that sword which is what we think of as graft versus leukemia effect, or in this case it would be graft versus MPN effect where some of those donor cells recognize the little differences between them and the MPN cells and wipe them out. And so, that’s really what you’re trying to do is allow that new immune system to find the bad actors and wipe them out. 

Andrew Schorr:          

Okay. You touched on something I think we’ve got to ask about and that is people are hearing in the blood cancers now the experimentaland in some cases an approved approach called CAR-T, chimeric antigen receptor T-cell therapy, but again immunotherapy to train the T cells to fight your ailment. What do you think about that in MPNs? Does it have promise?

Dr. Scandura:              

I mean, it definitely has promise. It’s been a challenge in myeloid disease as a whole, so AML, MDS, MPNs have not been the first diseases where this has been shown to be successful, more lymphomas where it has had a lot of traction and some nice responses. What it really is it’s a living drug and this can be done in a couple different ways. They can be cells from yourself that thenare treated in the laboratory so that they start recognizing these immune cells. You start tricking them into saying, “I’m going to attack this particular thing.” Even though they weren’t really trained to do that, they are now being tricked into doing that. 

And so, in a disease like a B-cell lymphoma, most of them express a particular protein that’s on B cells, CD19. So, if you take these CAR-T cells and you say, “Well, go out and kill everything you see that has CD19 on it”, it will wipe out a lot of those lymphoma cells. In myeloid diseases like MPNs, it’s a little harder. The targets are not so clear-cutand they’re shared with normal cells. There’s one area where I think it has the most promise is calreticulin because the mutation in calreticulin isn’t a tiny little mutation. It’s a mutation that causes a whole new end of the protein that doesn’t exist in the body otherwise.  

And some of the calreticulin actually gets onto the surface of the cells so it’s displayed to the immune system, and so this is an area where I think there’s some promise for CAR-T cells to target those calreticulin mutant cells. There may be other targets as well and I think we’ll learn as time goes along. People are trying to target molecule CD123, which is expressed on certain abnormal stem cells. The problem is it’s expressed at relatively low levels on those cells. It’s also expressed on normal cells and it’s expressed at higher levels on much more common cells. So, it makes it a somewhat imperfect target, and also difficult from a drug standpoint because there’s a lot of people wearing the same mask, only some of them you want to kill. So, it can be a problem.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on January 22, 2019