How stem cells can fight cancers, autoimmune diseases

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

Treatment options for certain cancer therapies and rheumatologic diseases may broaden through the use of stem cell transplants or therapies. Today I'll talk with Dr. Frank Zhou about this potential. He's the director of the stem cell transplants and cell therapies program at Upstate.

Host Amber Smith: Welcome to "The Informed Patient," Dr. Zhou.

Frank Zhou, MD: It's a pleasure.

Host Amber Smith: Can you describe what a stem cell transplant is and who it can help?

Frank Zhou, MD: So, as the name implies, we use stem cells, either from the patient themself or from a healthy donor, to use them to treat for different types of blood cancers. That's what we do.

Host Amber Smith: Let me ask you, if I can, what is a stem cell? How does it differ from other cells in our body?

Frank Zhou, MD: It's a very general term when we refer to stem cells. What we use here, for cancer treatment, in stem cell transplants, are hematopoietic stem cells, which means the stem cells that will differentiate into our blood cells in the bloodstream, eventually.

It's different from the stem cell in the general sense that people use this for tissue generations, but we only use hematopoietic stem cells.

Host Amber Smith: And what are the stem cell transplants used to treat?

Frank Zhou, MD: Primarily for different types of blood cancers, including lymphoma, myeloma and leukemia.

Host Amber Smith: And can you tell us how they're done? I know you said it can be with a donor blood or from the actual patient, right?

Frank Zhou, MD: Depending on the disease. For lymphoma and multiple myeloma, we oftentimes use patients' -- their own -- stem cells, once they were treated adequately from the beginning. When they're ready for stem cell transplants, we will collect their blood stem cells and reinfuse back to them after the transplantation.

Host Amber Smith: And this sounds like a specialized technique.

Frank Zhou, MD: It is. It may sound difficult by itself, but the steps are pretty simplified. When people had adequate treatment from the beginning, they're ready for the stem cell transplant. We will collect their stem cells first through a dialysis-machine type of machine.

While we collect enough of those cells, we can freeze them down. When the time comes, they're ready for transplant, they will be admitted to the hospital. At that point, we will get something called conditioning chemotherapy, which is a high-dose chemotherapy to eliminate all the disease in their marrows and elsewhere in their bodies, before they're ready to get the stem cells reinfused back to them.

So the whole process takes about two weeks to three weeks inside a hospital. And when the stem cell grows out, people are ready to be discharged home.

Host Amber Smith: So what is done to the stem cells, once they're extracted, before you give them back to the patient?

Frank Zhou, MD: They can be frozen down in the liquid nitrogen tank, and it can be kept for months to years, until the patients are ready to receive them back

Host Amber Smith: And when they receive them back, does this hopefully take the place of cancerous cells?

Frank Zhou, MD: Correct. So the chemotherapy we give to them, (which) we call the conditioning chemotherapy or preparative chemotherapy, is to wipe clean their diseased (bone) marrow to allow the healthy stem cells to be reinfused back.

In the case of leukemia, because the primary disease is in the bone marrow, we would not use their own stem cells for the transplant, but rather a healthy donor, matched donor cells, for the stem cell transplant.

Host Amber Smith: Are treatments like this generally covered by insurance?

Frank Zhou, MD: Correct. They're covered.

Host Amber Smith: And how long do the effects of a stem cell transplant last?

Frank Zhou, MD: If it's successful, it lasts lifelong. You gain your health back, and the disease is in remission. People can live as long as the stem cells are going to support them.

Host Amber Smith: How hard is it for you to find a match, someone who has stem cells that can be donated?

Frank Zhou, MD: If you need healthy donor cells, there are relatives who could be a potential genetic match to you. Or it could be healthy donors who volunteer themselves across the globe. There is an international donor database that allows us to find healthy donors for the patient.

Host Amber Smith: Are blood relatives always a match or not necessarily?

Frank Zhou, MD: Not necessarily. Statistically speaking, if you have the same parents, every one out of four siblings will be genetically identical to you, so they could be so-called matched sibling donors.

Then, across the donor registry, there are genetically comparable donors we could find, depending on ethnicity. For Caucasian/white people, the chance of finding a healthy donor from the registry is around 70% For other ethnicity people, the percentage varies. It is not because of less healthy donors from African Americans or Asians, it is because their genetic background is more admixed.

Host Amber Smith: So it's more of a challenge to find a match.

Frank Zhou, MD: There is a new technique being developed using "haploidentical" donors, meaning half-matched donors. So if older parents were diseased, having leukemia or other blood cancers, their children, by definition half-matched, now we have a technique to have their children to donate for them, or their sibling who is a half-match. So this is a significant advancement in the transplant world over the past 10 years.

Host Amber Smith: Do the recipients of stem cells, do they have to take anti-rejection medicine, like with organ donors and recipients?

Frank Zhou, MD: Correct. Obviously for autologous, meaning that (you) use your own stem cells, you don't need any immunosuppression medication because they're part of their own (body). For the allogeneic (from a donor) stem cell transplant, after the transplant, when those stem cells grow out, you do need immunosuppression medication this time -- we call it graft-versus-host disease -- to prevent it. This is the opposite of the organ transplant, in which case you reject an organ. But in the stem cell transplant, actually the bone marrow you receive is going to reject you, so that's what we are suppressing.

Host Amber Smith: If it's successful, the stem cell transplant, are the stem cells immune from developing cancer?

Frank Zhou, MD: So the stem cell that you receive from a healthy donor will keep you under check for those remaining cancer cells. They will seek out and kill them. Obviously, this goes hands in hand with graft-versus-host disease; we call it graft-versus-leukemia or -lymphoma effect.

That's a potential cure.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with assistant professor Dr. Frank Zhou from Upstate, where he directs the stem cell transplants and cell therapies program.

Can you walk us through the cell therapies that may be used to treat cancers or rheumatologic diseases?

Frank Zhou, MD: Yes. This is another exciting area, as we see a lot of development and advancement. Right now we have something called chimeric antigen receptor T cells. Those were bioengineered T cells from the patient we collect. And then those cells were manipulated in the laboratory to have them recognize the cancer cells and engage them through the receptor expression on the cell surface.

When you infuse those cells back to the patient, those particular T cells can seek out their cancer cells, engage them and kill them.

Host Amber Smith: Is that also the one that's called CAR-T cell?

Frank Zhou, MD: Correct. C-A-R dash T (which stands for) chimeric antigen receptor T cells.

Host Amber Smith: Did I read recently that they're looking at that for lupus as well?

Frank Zhou, MD: This is another interesting area to see more development and usage of this treatment modality. It originated from treatment for cancers. Now the CAR-T can also manipulate the immune system of the patients who suffer from autoimmune disease, such as lupus or rheumatoid arthritis.

Host Amber Smith: Now, what about adoptive transfer of regulatory T cells? What is that?

Frank Zhou, MD: It's very similar to the chimeric antigen T cells therapy. In which case, those regulatory T cells can regulate your immune system by interacting with the rest of your immune cells in the body just to restore a homeostasis, a balance in your immune system to treat or to prevent autoimmune disease.

Host Amber Smith: In general, how effective are these therapies and how long do they last?

Frank Zhou, MD: So when CAR-T therapies are used for blood cancers, they are also a potential cure for that, theoretically, as long as those T cells can last inside the body a long period of time and also kill any cancer cells that have resurfaced.

In the matter of years, the median survival currently for CAR-T therapy in lymphoma and leukemia patients, we see median survival more than two years, that was revealed from the study. In the real world, we also see longer remission, more than two years.

Host Amber Smith: Interesting. Are these useful in children?

Frank Zhou, MD: It is, although I'm an adult cancer doctor, but I heard my colleagues in the children's hospital also exploring the CAR-T therapy approach, as well as the allogeneic transplant approach for the past few decades, for children's blood cancers.

Host Amber Smith: What other therapies do you see on the horizon?

Frank Zhou, MD: So there are a lot of improvements of the CAR-T cell itself, by how you construct the cells, how you bioengineer the cells, how you make them more potent, how you reduce side effects from them. So there are a lot of things that can be done and more work to do.

Host Amber Smith: When you got started in medicine and scientific research, did you think or anticipate that there could be such development with stem cells?

Frank Zhou, MD: It's certainly a surprising, pleasant surprise. When I was a fellow (receiving specialized training) ) almost 10 years ago, the CAR-T therapy was not there. Look at right now what we have, and I'm looking forward. That's exciting for us, as a cancer doctor, and also it's a blessing to our cancer patients.

Host Amber Smith: I don't often get to interview people that use the word "cure." So that's encouraging.

Frank Zhou, MD: Yes. That's the goal we are shooting for, although not everyone is cured, but theoretically, those approaches can offer a cure to our cancer patients.

Host Amber Smith: Well, Dr. Zhou, I appreciate you making time for this interview. Thank you.

Frank Zhou, MD: Thank you. It's my pleasure.

Host Amber Smith: My guest has been Dr. Frank Zhou. He's the director of Upstate's stem cell transplants and cell therapies program.

"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe, with sound engineering by Bill Broeckel and graphic design by Dan Cameron.

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