Blood stem cell transplants have played a central role in the treatment of blood cancer for decades. These procedures can increase patients’ chances of survival and in some cases even offer the possibility of a cure. But over the past decade, doctors say they have started performing transplants for fewer types of cancer, especially lymphomas, and are instead seeking first newer immune or targeted therapies that are safer and often more effective.
That’s progress that experts hope will continue. “I know from my time as a transplanter that there was nothing better than when a patient didn’t need to be transplanted,” said Andy Kolb, president and CEO of the Leukemia and Lymphoma Society. “Because it’s poisonous.”
There are generally two types of stem cell transplants, also called bone marrow transplants or hematopoietic stem cell transplants: autologous transplants and allogeneic transplants. The shift away from both types of transplants has not been the same for all types of cancer, experts added. with the number of allogeneic transplants for certain malignancies even increasing.
Autologous transplants involve harvesting a patient’s own stem cells and returning them after the patient has received a massive dose of chemotherapy. These are commonly used for myeloma and for many lymphomas. The theory behind autologous transplants was to give the patient as much chemotherapy as doctors could to eradicate the cancer, but that would also destroy the patient’s bone marrow, where blood stem cells reside. That can make the patient dangerously susceptible to things like infections and other complications.
“It really is a sledgehammer-like treatment. It’s a very high dose of chemotherapy, and then stem cells to recover from it,” said Timothy Fenske, a physician and cancer researcher at the Medical College of Wisconsin. “You see 1-3% of patients die from complications while they’re going through it. It’s not something trivial that people have to go through.”
The other type of stem cell transplant is an allogeneic transplant, in which a healthy donor provides stem cells to the patient. These are most commonly used in certain myeloid malignancies such as acute myeloid leukemia. These procedures still use chemotherapy, but it is generally not as intense as autologous transplantation.
The idea here is that once a cancer patient is in remission, the healthy immune system from a donor’s blood stem cells will help clear out the remaining cancer cells in the patient’s body – something called the graft versus cancer effect. The downside of allogeneic transplants is that there is a chance that the grafted immune system will reject its new host and attack the patient, a dangerous and sometimes fatal complication known as graft versus host disease.
Between the two, the decline in autologous transplants in recent years has been much more dramatic than that of allogeneic transplants, experts say. “Technology has emerged and new targeted small molecules such as tyrosine kinase inhibitors, bispecifics and CAR-T have definitively changed the landscape. That happened mainly with autologous transplants,” said Steven Devine, the CMO of NMDP, formerly known as the National Marrow Donor Program.
The biggest change has been “an explosion of CAR-T,” says Mikkael Sekeres, chief of hematology at Sylvester Cancer Center in Miami. CAR T-cell therapy involves engineering patients’ own immune cells to find and kill cancer cells, experts told STAT.
Recent studies have shown that CAR T cells were superior to autologous transplantation in many lymphomas, including follicular and large B-cell lymphoma. In the past year, two clinical trials showed that autologous transplantation also had no benefit for mantle cell lymphoma patients who had achieved an initial, deep remission after initial therapy thanks to immune therapies such as CAR T cells or targeted therapies. That has deterred many lymphoma doctors from performing autologous transplantation for certain patients.
“We’re really getting rid of it,” says Elise Chong, a hematologist-oncologist and researcher at the University of Pennsylvania. “It may still be appropriate for some patients, but the overall number we offer is significantly lower. It is definitely progress.”
Autologous transplants are also down for multiple myeloma, but only slightly, according to data from the Center for International Blood and Bone Marrow Transplantation Research. Autologous transplants are still very commonly performed for myeloma, but that may change if ongoing studies of CAR-T in myeloma show it to be superior to transplantation, says Irene Ghobrial, a multiple myeloma physician and researcher at Dana-Farber Cancer Institute.
“It’s a big debate again. Whether the CAR-T trial is positive or not is something we will likely find out in the coming years. But that could change for the first time and say we shouldn’t transplant our patients,” she said. “But currently, autologous transplantation is still the standard treatment for myeloma.”
The story for allogeneic transplants is also slightly different, says NMDP’s Devine. There are some types of cancer where allogeneic transplantation is no longer used – particularly certain chronic diseases such as chronic lymphocytic leukemia and chronic myelogenous leukemia (CML). “CML is the great example. Until the late 1990s, this was the most common indication for allogeneic. Then came Gleevec, and now we are doing two to three hundred transplants for CML in the US,” Devine said. Gleevec is a targeted therapy from Novartis used for certain blood and solid cancers.
But allogeneic transplants remain one of the best options for curative therapy for other cancers, such as acute myeloid leukemia. Allogeneic transplants have also become safer over the years, Devine added, making it possible to perform in older patients and perform more transplants with unmatched donors without sacrificing efficacy or safety. “According to our operational data, allogeneic transplants are growing at approximately 7-8% per year,” Devine said. “What has really fueled this is the growth in the number of mismatched, unrelated transplants. That’s starting to take off.”
Researchers are working to find ways to do this CAR-T and other new therapies effective in myeloid malignancies such as acute myeloid leukemia, which could one day also lead to a reduction in the number of transplants in these cancers. Still, Devine said that despite all the progress over the past decade, there are still patients who relapse or don’t respond to immunotherapies and targeted therapies — and there will continue to be such patients in the future.
“It’s still an important option,” he said. “I don’t see transplantation ever going away completely.”