RRH Harnesses Stem Cells’ Potential to Treat Cancers

Randi Minetor

If you have been waiting for decades to see if stem cells turn out to be the new frontier of disease treatment, we now have the answer. It’s a resounding yes, said Anne Renteria, MD, Rochester Regional Health’s Medical Director of the Acute Leukemia & Stem Cell Transplant and Cellular Therapy programs at the Lipson Cancer Institute.

“I always tell my kids that I live in a sci-fi world,” she said. “It is very complex and very specialized, but what we are doing is bringing Rochester Regional Health (RRH) very community-based access to cell therapies and bone marrow transplants.”

Stem cells, produced by the bone marrow, have the ability to turn into all three of the types of blood cells that the human body requires to function. This capability can be lifesaving to people with one of several kinds of blood cancer, such as acute leukemia or lymphoma, and also those who have undergone high-dose chemotherapy.

“Some of the chemo is so strong that it will bring the blood counts all the way down to zero,” said Dr. Renteria. “If you leave it like that, there’s a good chance the counts will never recover. So we infuse back their own stem cells after they receive high-dose chemo.”

There are two modalities of stem cell transplant—and in either case, the patient’s cancer should be in remission before the transplant.

An allogenic transplant involves finding a donor who is a perfect or near-perfect match for the patient, so that they can donate stem cells from their own bone marrow to restore the patient’s immune system. “We have to identify someone who is perfectly matched, and those stem cells are infused in the patient,” said Dr. Renteria. “So we need to first treat the cancer, then administer a conditioning chemo followed by immunosuppressive therapy to make sure that the patient can accept and allow the buildup of the new and foreign stem cells in their body. These new and foreign stem cells have the mission to build a new immune system.”

An autologous transplant, also called high-dose chemo followed by stem cell rescue, involves collecting the patient’s own stem cells after the patient has been treated with chemotherapy, when, for example, the multiple myeloma has been defeated and the patient’s bone marrow is close to free of cancer. Even though the disease has been arrested, the bone marrow after receiving a high-dose chemo may be so suppressed that it will be unable to generate the blood cells the body needs for a healthy recovery. “The patient’s stem cells are typically collected four to six weeks ahead of the transplant procedure, then preserved in liquid nitrogen,” said Dr. Renteria. “They are therefore ready to use when we proceed with the transplant procedure.”

Dr. Renteria is the Medical Director of our Acute Leukemia & Stem Cell Transplant and Cellular Therapy Programs.

Autologous transplant provides important advantages over an allogeneic transplant, which relies on donor stem cells. The collected stem cells are ready for use at exactly the right time, eliminating the time-consuming process of finding a relative or other donor who is a perfect or nearperfect match to the patient. Even more important, a patient whose immune system is already depleted does not need to worry about rejecting the donor’s stem cells, so no harsh immunosuppression therapy is required.

Creating a stem cell program at RRH

“There are many new transplant centers growing in the country right now,” said Dr. Renteria. “Everywhere you go, there’s a transplant center coming to life.”

She had deep background in this new treatment modality before coming to Rochester, as the leader of acute lymphoblastic leukemia research and clinical service and assistant professor of medicine at the Icahn School of Medicine at the Mount Sinai Hospital system in New York City. She completed a fellowship in Blood and Marrow Transplantation at the Mount Sinai School of Medicine, and she served in the department of hematology oncology at Boston University School of Medicine before taking the position at Mount Sinai. Most recently, Dr. Renteria was the Medical Director of Medical Affairs at ICON PLC, a clinical research organization conducting clinical trials in hematology oncology as well as cellular and gene therapies. “I had been approached by several different companies,” she said, “but I chose RRH because of the support that they were offering. They had just built the Sands-Constellation Center for Critical Care, with a dedicated Oncology inpatient floor with 36 private rooms, 18 of them being positive pressure rooms,” rooms that maintain a higher air pressure than their surrounding environment. Positive pressure rooms allow air to leave the room without recirculating back in, keeping contaminants from entering the room and protecting patients with compromised immune systems from airborne infections. Some of these rooms at the new center can be converted to negative pressure rooms, which keep infectious bacteria and viruses from leaving the patient’s room, isolating the patient and their illness. “They had already started investing in this crucial infrastructure,” she said, “so they were committed to treating this population of patients.”

Before building the Sands-Constellation Center, RRH had general oncologists on staff who took care of patients with many different kinds of cancers. When it came to acute leukemias, however, they most of the time referred patients to specialized centers like the Wilmot Cancer Center at the University of Rochester Medical Center, or Roswell Park Cancer Center in Buffalo. “Those centers had the systems to support the patient through a very, very intense and specialized treatment,” said Dr. Renteria. “So in starting a program, we had to increase the complexity of the therapy we can offer the patients, and then build the system to support that.”

Even with the investment in new facilities, however, adding the ability to treat acute leukemia and lymphoma patients required much more. “How do we get a center that does this kind of thing up and running?” said Dr. Renteria. “The nurses, the APPs, and the doctors all needed to be trained for that. We needed a very efficient and strong support system for patients, so we needed social workers, a clinical navigator, a bone marrow transplant coordinator. It takes a village.”

Many staff members are bilingual in Spanish—Dr. Renteria herself speaks four languages—and they are mindful of the situations patients may be in at home, and how they can help bridge the gaps they may encounter as they undergo treatment. For example, “We have a very strong representation of patients that are farmers,” she said. “One of our APPs is a farmer herself. She understands the needs of the population, the gaps that must be bridged. Our staff at RGH really understands what patients are going through socially as well as medically.” Dr. Renteria arrived in late November 2020, and started assembling the team immediately. “At that time, Rochester General Hospital was seeing and managing approximately one patient with acute leukemia per month and since I joined at the end of November last year, this number has already significantly increased. And all our patients are being treated in-house.”

With the team in place and their specialized training completed, RRH is working toward performing its first autologous stem cell transplant procedure at the end of October. “We are already treating our patients with the indicated and very, very complex modalities of regimens,” she said. “The clinic is opening more days per week, and extending its hours. We are in continuous communication with different specialties, including blood bank and pathology, to make sure we have the transfusion management doctor to collect the stem cells. We have involved the National Marrow Donor Program. It’s another level of care and coordination.”

On the horizon

Dr. Renteria and her staff are already looking ahead to additional therapies that this highly specialized team can offer patients. One of these, chimeric antigen receptor (CAR) T-cell therapy, alters the genes inside of immune cells known as T cells to attack cancer cells and destroy them. The CAR

is a manufactured receptor that helps the T cell identify the targeted cancer cells. This innovation can help treat some cancers even when chemotherapy hasn’t been effective. This technology requires collection of white blood cells, which contain the T cells, and separating the T cells from these white cells. A laboratory then adds the CAR, turning these T cell into CAR T cells. The cells remain in the lab for several weeks to multiply enough cells for the therapy to be effective.

The patient then undergoes mild chemotherapy to lower the number of immune cells in their body before receiving the CAR T cells. Once the patient receives them, the cells go to work binding with cancer cells and killing them, while multiplying further to disable even more of the cancer.

As the cells multiply, however, they may release chemicals into the blood called cytokines. These chemicals can boost the immune system into high gear, causing a number of symptoms that mimic a serious infection. When these symptoms become severe, they require treatment in the intensive care unit, where specialists trained in treating cytokine release syndrome (CRS) work to bring it under control.

“It’s another layer and level of training,” said Dr. Renteria. “We need to get everyone on the team aligned, have mock sessions with mock patients, make sure we are all coordinated and on the same page. We need to train people in the ED, so they can recognize CRS, know what is going on, and who to call as well. The ICU needs to be on board, because CRS has to be treated in the ICU. It’s 100 percent reversible with the proper care.” The first CAR T cell procedures could take place as soon as early 2022.

“Rochester General Hospital is really an amazing place,” she added. “Six months after I got here, look at where we are. A lot of my colleagues said, ‘You’re crazy, this is never going to take off, you need a full commitment from the leadership. You have to set up everything.’ I discussed this with the leadership here prior to my coming. I wanted to be able to come to a place that would support what I do, and they are completely on board and invested in supporting our community in their most diverse needs.”

Randi Minetor is the author of Medical Tests in Context: Innovations and Insights (Greenwood, 2019) and is a freelance journalist based in Rochester.