Park on Transplant Eligibility for Patients With Cancer

Soyoung Park, MD

While transplant remains the standard of care for many hematologic malignancies, experts are noting the appeal of chimeric antigen receptor (CAR) T-cell therapy. These next-generation treatments could change the golden standard, according to Soyoung Park, MD.

“We are utilizing a lot of the techniques that we used for a collection of stem cells, but it's used for a more kind of immunotherapy type purpose. We're not collecting the stem cells themselves; we're actually collecting the T lymphocyte cells. What happens is that the patient's own T lymphocyte cells, which are normally in everyone's bodies, are responsible for usually recognizing viral infections and attacking those and triggering an immune response,” said Park, hematologic oncologist at City of Hope Phoenix, in an interview with Targeted Oncology™.

In the interview, Park, discusses the criteria used for determining transplant eligibility and choosing between the different types of transplants for patients with cancer.

Targeted Oncology: Can you discuss transplant eligibility and the different determining factors that go into that?

Park: We have patients undergo various screening tests and certain blood tests for infectious disease, antibodies, echocardiogram, chest X ray, pulmonary function tests to assess the physiologic state of their heart. Is their pumping function good? Is their lung function good? Because a lot of that is going to help us assess how high-risk they will be, if they were to go undergo a transplant, and this could help us determine if we need to make any dose adjustments to chemotherapy, is it a good idea to even transplant them if they have a not well functioning heart or lungs? There's a variety of tests that we do to evaluate the patient before they go to the point of undergoing a transplant.

Most institutions across the board don’t have black and white criteria. Usually, it's a discussion. Usually, most institutions say absolutely not, this is not safe to consider, even for a transplant, and then there are some patients when the testing results where they're kind of in a gray area. That would require more discussion with other transplant center doctors, where we may discuss with someone who's more experienced to get an idea. With these test results and in conjunction with the patient's medical history, not every center does this, but I think it's more commonly utilized what's called an HCT, which is a term for stem cell transplant, comorbidity index scoring, so HCT-CI score. We can document in records, and that would give people an idea of how high-risk this person is and becoming very ill during the transplant process.

Other aspects are depending on the disease state, including where they are, if transplant is appropriate, considering where they are with their disease because the criteria is different for different types of disease. For instance, for multiple myeloma, autologous stem cell transplant is part of the standard of care. Most patients, as long as they are healthy, will generally go through an autologous stem cell transplant after they go through their initial induction treatment. Not all patients with lymphomas, more aggressive type lymphomas, would undergo transplant. It has only shown benefit when they undergo transplant when they've relapsed. If they've already gone through a round of chemotherapy, and they've shown they've had disease remission, and it's not coming back, those patients would not go to transplant. If the disease does come back and they require more chemotherapy, there's a benefit to do transplant after that to increase their survival.

What questions still exist regarding transplant eligibility?

Now as the population continues to age, the challenge is, is there an age cut off for who should undergo transplant or who shouldn't. There are 2 different types of transplants there. First is the autologous type of transplants where essentially the patient's own stem cells are given back to them. It is not a transplant in the true definition sense of a transplant. It's more of a stem cell rescue because it's to help boost the bone marrow and support the bone marrow as a patient recovers from the effects of chemotherapy they got as their conditioning regimen to the transplant. The allogeneic transplants are what a true transplant is because those are the ones where patients get stem cells from other donors. That is mechanistically working as a transplant. The stem cells are reacclimating and that becomes the patient's new kind of blood stem cells that grow in the body.

I think often the issue is that because with an aging population, we are getting older and older patients who get diagnosed with these various malignant hematology diseases, they actually need transplants, but sometimes with age, most doctors are hesitant to transplant because we are not confident that they're going to do well knowing what the chemotherapy conditioning regimens do. Age is still a limitation, but sometimes these patients become a big discussion if they're healthy, 75 and above patients, so I think those pose challenges and still bring up questions as to whether these patients are eligible. Is age the only thing that would deter us from doing transplant? Generally, patients who get autologous transplants push a little higher in age. We may consider someone 80 and above, because the adverse reaction risk is much less than an allogeneic transplant where it's rare for someone to consider above 80. Now there are more treatment regimens for someone above 80 for more aggressive leukemias, so it's being less considered for transplant. Still, age is a question for where we draw the line, and it's usually multifactorial. It's not just that this age should not get a transplant.

Can you talk about the transplant types that are kind of most successful in today's landscape?

Autologous and allogeneic are utilized very differently, so you can't compare the success of the 2 because they're used for various diseases. But if you were talking about peripheral blood stem cell transplant vs bone marrow stem cell transplant vs cord blood stem cell transplant, the most utilized of those is the peripheral blood stem cell transplant. While we use bone marrow transplant and stem cell transplant a little bit interchangeably, if we were to really get more technical, when we're doing transplant, we're talking about peripheral blood stem cell transplant, meaning the patient's go through a process where their bone marrow is stimulated to release their stem cells into circulation. Then it is collected through a process called apheresis, which is similar to dialysis. The blood gets filtered through and then the stem cells get collected, but it's been shown in various studies that peripheral blood stem cells engraft faster and better than bone marrow stem cells, which is important because that'll shorten the process when patients go through stem cell transplant. They'll become where they have no immune system and they're extremely vulnerable to infection. But when they engraft, that time gets shortened, and if they have a peripheral blood stem cell transplant, and that's the grafting is faster vs a bone marrow stem cell transplant which we don't utilize as much.

Also, peripheral blood stem cell transplant, what it does is the stem cells continue to attack whatever kind of existing blood disease was already there. There is a risk of what's called graft-vs-host disease after stem cell transplant, but it's also providing what's called graft-vs-leukemia disease for all the patients who get these kinds of peripheral blood stem cell transplants. It continues to have that ongoing effect of killing off the disease. That effect is not really existing with bone marrow stem cell transplant. It doesn't graft, but usually, it won't have a significant effect where it will continue to attack the patient's existing disease, so then the risk of relapse is there. That's why it is not the preferred method for a lot of these different diseases for patients who get transplants.

Then we have what's called cord blood transplant. At least in the adult world, there have been a lot of complications with cord blood transplant. They do not engraft quickly and because they take so long to engraft, patients continue to be vulnerable to infection. They get infected a lot, which becomes very complicated to manage, so it's fallen out of favor. I would say the kind that is most utilized is peripheral stem cell transplant because of the fast engraftment, but there are a few rare blood diseases where it is preferred to use a bone marrow transplant. The difference for a peripheral blood stem cell transplant is that the patient goes to an OR and then the stem cell transplant physicians do what's called a harvest where we go in and draw out the bone marrow ourselves. We get the needle and syringe and go into the bone marrow and get the blood stem cells out directly, rather than collecting them in circulation.

Can you discuss some of the novel transplant strategies that are showing promise? What are your hopes for the future of this space?

The biggest is chimeric antigen receptor therapy. We are utilizing a lot of the techniques that we used for a collection of stem cells, but it's used for a more kind of immunotherapy type purpose. We're not collecting the stem cells themselves; we're actually collecting the T lymphocyte cells. What happens is that the patient's own T lymphocyte cells, which are normally in everyone's bodies, are responsible for usually recognizing viral infections and attacking those and triggering an immune response, what's happening now is that these cells can be then altered to recognize a marker on various types of blood cancers. When it recognizes that, it'll lock in with another marker on another immune regulating cell, and it'll trigger our immune system to recognize the cancer in the body. It stimulates the immune system to attack the cancer. It's similar in the sense that we still go through the collection of the cells, but this time it is T lymphocytes and not stem cells. That's been approved for various types of lymphomas and for multiple myeloma. There's still a lot of ongoing trials on how to manage the adverse effects.

That's up and coming, but there's a lot of discussion on patients who need transplant, how to sequence it, how to piece it in, because when you think about it, they're not working in the same way. Transplant is immunosuppressive, whereas CAR T is immune stimulating. It's not to say 1 is better than the other, each has their role, but where do you place each because certain patients might have extremely aggressive disease that is progressing fast and there might not even be time to get to a transplant. Those patients might do better with CAR T therapy because CAR T, once it's in the system, continues to stimulate the immune system to attack the cancer whereas stem cells are kind of a 1-time thing. Along with CAR T cells, bispecific engager therapy, although those aren't stem cells, it's also a form of immunotherapy. It's controlled by a molecule, not so much the cells. Instead of calling it a bone marrow transplant, it is more of cellular therapy.

What advice do you have for community oncologists?

Whenever there's a question of whether someone should get a transplant or not, it's better to refer earlier to a transplant specialist than later because you want the patient connected while they're on chemotherapy for relapsed disease, and they eventually will need a transplant. It is better to refer to them earlier before they are at the end of that treatment because that can lead to delays. It is better to determine from the beginning if this patient would be eligible for transplant or not, rather than figuring that out later, because it might be that they are eligible and now you have lost some time. In that time, there's always a chance of the disease coming back when they're on a break from their chemotherapy. I'd say it's always important when oncologists want to refer a patient for transplant as early as possible when there's any question of the need of transplant.

REFERENCE:

What’s the difference? Autologous and allogeneic stem cell transplants. News release. City of Hope. August 19, 2023. Accessed June 21, 2023.https://tinyurl.com/25px2xkx