Treating Sickle Cell Disease With HSCT

Ify Osunkwo, MD, MPH: We know that there is a cure for sickle cell disease, most people think there is not, but there actually is a cure. It’s been around for about 30 years-plus, and it’s stem cell transplantation. Dr Heeney, give us your ideas of why you would consider transfusions for a sickle cell individual. Who should get it?

Julie Kanter, MD: For transfusions?

Ify Osunkwo, MD, MPH: For transplant. Who should get a transplant for sickle cell disease, and what does that process look like?

Matthew Heeney, MD: Well, there are a number of types of stem cell transplantation that can potentially cure patients with sickle cell disease. It essentially depends on the source or the donor of the hematopoietic stem cell transplant cells. There are characteristics of the recipients that are also important. In terms of the donor, probably the optimal donor would be an HLA [human leukocyte antigen] match, or an immunologically identical person, and that’s generally a sibling, a full sibling, same mother and same father.

But there’s only about a 1-in-6 chance with each full sibling that they’ll be HLA identical. The big stumbling block with that is that most patients don’t have a donor. Alternative donors would be a matched unrelated donor, or potentially even a haploidentical, meaning a half identical, family member. These are becoming of interest now, but generally have overall slightly worse outcome, although there are certainly some advances being made in those alternative donor transplants.

I think that really what’s pretty clear from the literature now is that hematopoietic stem cell transplantation has a much better outcome if it’s done early in life. I think certainly under age 10, and some say under age 8 or even 5, would be the optimal time to do it. The challenge is that at that young age you may not have the family’s experience to want to undergo such a procedure that could have some morbidity or even mortality.

Currently with the HLA identical sibling transplant, we describe disease-free survival or overall survival of over 90% in most academic medical centers. While there is quite a lot of hope for that procedure, there still is some morbidity and mortality associated both in the acute transplant period and in the follow-up period.

Ify Osunkwo, MD, MPH: Nirmish, what are the benefits? Why would a sickle cell individual seek out a transplant? Why would you consider referring an individual with sickle cell disease for a stem cell transplantation?

Nirmish Shah, MD: I think it goes back to what Matt was bringing up, that we know that the benefits are better when the patient is younger. However, we have to balance the idea that there are definite risks of mortality. Patients may die with this procedure. Then we’re trying to find patients who basically start to have issues that then start to outweigh the risks that we are going to have this patient go through. Those include patients who are having strokes, patients who are having recurrent acute chest syndrome.

Patients who have severe disease, as classified by 1 of those type of complications, and then you again try to get those patients as early as possible. Then you make a referral, and then again that’s when you start to try and make the decision, well how much risk is that family willing to take? How much comfort do we have in having them refer to, outside of a matched sibling donor, to a clinical trial for a matched unrelated, cord blood, etcetera. I think we are making a lot of progress. It is a curative therapy, so the reason they go for this is that they have severe disease as defined by some complication, and we’re worried that we’re going to have progressive disease and they’re going to have a higher mortality, and we really need to pursue some other option.

Ify Osunkwo, MD, MPH: Julie, for adults with sickle cell disease, does that mean that they don’t have options, they don’t have the potential to be cured? What can we say to our adult patients in terms of your potential opportunity for a curative therapy?

Julie Kanter, MD: It’s really exciting. We’ve done some new work in different chemotherapy models. We know to give a transplant we have to make room in the bone marrow. We have to give chemotherapy in some capacity, which clears space for the new bone marrow. Starting with a group at NIH [National Institutes of Health] and followed by several others, they’ve done some trials with adults where we can use a little less chemotherapy and still get great outcomes.

In fact, 1 of the NIH trials, outcomes were almost as good as the kids, right about 90% event-free survival and curative therapy. We also know that the haploidentical program, which uses a little bit less chemotherapy and uses what we consider more immunologic-mediated therapy, is also useful in adults. There are ongoing studies, and I certainly would suggest if individuals are thinking about this that they stay on the clinical trials so we get as much data as possible, so that we can make this better and better. I think more and more these curative options are available to adults.

Ify Osunkwo, MD, MPH: There is hope. Biree, you are also an adult hematologist. Who would you not refer to transplant, and who would you refer over the age of 20, on the adult side?

Biree Andemariam, MD: Well, I agree with what Dr Shah said in terms of who you would refer. I think those individuals who have very few manifestations of chronic organ damage and are rarely affected by vaso-occlusive pain crises, I don’t think that those patients would necessarily benefit from the risks associated with undergoing a bone marrow transplant. But I have the discussion with them, certainly. I think we all appreciate that everyone with sickle cell disease is facing a shortened survival, and I think that the risk-benefit ratio really does need to be discussed with the patient because ultimately they’re the ones who are going to decide which way they want to go.

I will say though having sent several adults, including those in their 40s, late 40s, for curative bone marrow transplantation, I think one of the things that we need to appreciate is that after 20, 30, 40-plus years of living with sickle cell disease, there’s a lot of chronic pain and a lot of chronic organ damage.

Patients post-transplant who suffered some of these problems expect them all to go away, particularly the chronic pain, a lot of it associated with avascular necrosis of the joints or destruction of the joints. And it simply does not fix the chronic pain in most circumstances. Another thing that’s emerging is the psychological effects of living with the disease and then not having it anymore. Believe it or not, that is psychologically problematic for a lot of adults with sickle cell disease. So much of their identity as a person has been wrapped up in living with the disease, and trying to live despite the disease.

Ify Osunkwo, MD, MPH: They don’t know what to do with themselves.

Biree Andemariam, MD: They don’t know what to do with themselves. A lot of them haven’t gotten to where they wanted to in life, and for the very first time are thinking long and hard about that. What’s next? A lot of them still live at home, may not have employment, may not have the education or the tools to go out and get a job that can help them provide for themselves. It’s complicated.

Transcript edited for clarity.