ASH 2013 - New Orleans, LA, USA
Comment: Transplantation and short telomeres increase the risk of cognitive impairment
Dr Jeffrey Miller - University of Minnesota, Minneapolis, USA
A lot of us have known about cognitive impairment after transplants. First and foremost I’ve been in the transplant field for more than twenty years now and we always hear from patients that their ability to think and do tasks, especially some of these higher level executive tasks that she was talking about, is definitely deficient. The work that Dr Bhatia has done in a very, very thoughtful way is to try to quantify this. The problem we have is these measures are not trivial to measure. What she has certainly identified is a difference in these cognitive impairments between those that get full intensity transplants and those that get reduced intensity transplants. So this is very important. We talked about some of these questions at the end – how does one make a decision about who gets one preparative regimen? Right now older people get reduced intensity transplants which gives you less cognitive impairment but all the young ones get these full prep transplants and we may need to think about how to best tie in all these endpoints into this equation.
What differences have you found between men and women in the data?
I don’t think we know all the variables. Obviously we know that there are genetic differences between males and females more than just appearance. Whether this be the way that metabolism affects how you tolerate therapies, how you tolerate chemotherapy, how you may tolerate tissue repair, so I don’t even think she knows yet. Remember, her measures are to show that the measures are real, they’re related to the preparative regimen. Some of these differences that come out with male or female sex need further explanation for us to understand because we’re all very, very different. Patients are very heterogeneous, males and females, and we need to learn more. Now that we have these measures I think we can precisely try to better understand the research.
What’s the best advice for these patients given their circumstances?
The answer that Dr Bhatia gave to a very similar question is that the intensity of going through a transplant is really aimed to cure patients of their underlying disease and right now the decisions are all based on that. We know that if you get a full preparative regimen your chances of relapse are much, much lower than if you get these reduced intensity preparative regimens. It’s really hard without further information to balance how we determine preparative regimens and lowering them if relapse rates are higher. The big challenge in the field is if we had a perfect way to give reduced intensity transplant to stimulate the immune system based on some of the other talks that we’ve heard about and if we can get rid of the relapse problem then eventually everybody should get reduced intensity transplants to make sure that we can think appropriately long term.
Patients come to me with the idea that I have leukaemia or I have some reason to really need a transplant. Our decision making is solely based right now on what’s the best probability of getting long-term disease free survival and get rid of the underlying malignancy. What Dr Bhatia has done is identified an important problem that we have to eventually put into the mix but it’s really, really hard to precisely measure cognition effects with how do you cure somebody with a transplant. Right now there has been heightened awareness about all these long-term complications. We need to understand the mechanisms. Maybe we’ll learn about protective drugs to lessen the effects of the high dose chemotherapy. It’s too hard to do a big procedure like transplant and not to think of cure as your underlying goal and I think that that was her answer as well. What this has done is opened up an avenue for further research in looking for those protective drugs that maybe will protect patients from some of these side effects with the higher dose preparative regimens.
