ACTRIMS 2026 | Key remaining questions regarding HSCT in MS: procedure and effectiveness in treating PIRA

Yeah, so I would say that the remaining questions fall into two categories. One is sort of procedural questions. Every institution that performs hematopoietic stem cell transplant has its own protocol, its own recipe. And there’s a lot of debate in the transplant field as to what’s the best way to perform the procedure, particularly what’s the most appropriate conditioning regimen. So this is the high-potency chemotherapy that’s used to eliminate the existing immune system. That’s the basis of the efficacy of hematopoietic stem cell transplant. And what conditioning regimen is the optimal tradeoff between potency and safety and tolerability still is somewhat unclear. And then all the other components of the protocol also have some uncertainty. So that’s one remaining question is, what’s the best way to perform the procedure? And then I would say the other big question is how effective transplant is for what’s been called PIRA, or progression independent of relapse activity. So we’re now pretty certain that transplant does not work in very severe, longstanding, non-active, progressive multiple sclerosis where there have been patients, even with relapsing MS, early relapsing MS experience, despite treatment with a high-efficacy therapy. If one assesses those patients carefully, it’s not uncommon to see some very subtle evidence of worsening. And the precise mechanisms for that are not clear. They’re probably different than what drives progression later in the disease. And so I think a big question is whether transplant would be effective for that aspect of the disease. We know that our currently available medications are not very effective for that.

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