Blood stem cell transplants have been central players in treating blood cancers for decades. These procedures can improve patients' chances of survival and can even offer the opportunity for a cure in some cases. But over the last decade, physicians say they've started doing transplants for fewer cancer types, particularly lymphomas, and are instead reaching first for newer immune or targeted therapies that are safer and often more effective.
That's progress that experts hope will continue. "I know from my days as a transplanter, there was nothing better than when a patient didn't have to be transplanted," said Andy Kolb, the president and CEO of the Leukemia and Lymphoma Society. "Because it's toxic."
There are generally two kinds of stem cell transplants, which are also sometimes called bone marrow transplants or hematopoietic stem cell transplants: autologous transplants and allogeneic transplants.The shift away from both kinds of transplants has not been even across all cancer types, experts added, with allogeneic transplants actually increasing in number for certain malignancies.
Autologous transplants are when a patient's own stem cells are harvested and given back to them after the patient has received a massive dose of chemotherapy. These have been commonly used for myeloma as well as many lymphomas. The theory behind autologous transplants was to give the patient as much chemotherapy as doctors possibly could to wipe out the cancer, but that would also obliterate the patient's bone marrow, where blood stem cells reside. That can leave the patient dangerously susceptible to things like infections and other complications.
"It's really a sledgehammer-type treatment. It's a really high dose of chemotherapy, and then stem cells just to recover from it," said Timothy Fenske, a physician and cancer researcher at the Medical College of Wisconsin. "You have 1-3% of patients die from complications as they go through it. It's not a trivial thing for people to go through."
The other type of stem cell transplant is an allogeneic transplant, where a healthy donor provides stem cells to the patient. These are most commonly used in certain myeloid malignancies like acute myeloid leukemia. Chemotherapy is still used in these procedures, but it's generally not as intense as autologous transplant.
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 mop up any remaining cancer cells in the patient's body -- something called the graft versus cancer effect. The flip side of allogeneic transplants is there's a chance the engrafted immune system might reject its new host and start attacking the patient, a dangerous and sometimes fatal complication known as graft versus host disease.
Between the two, autologous transplants have been on a far more dramatic decline than allogeneic transplants in recent years, experts said. "Tech has emerged and new targeted small molecules like tyrosine kinase inhibitors, bispecifics, and CAR-T have definitely changed the landscape. That's mostly been in autologous transplantation," 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," said Mikkael Sekeres, the chief of hematology at the Sylvester Cancer Center in Miami. In CAR-T cell therapy, patients' own immune cells are engineered to find and kill cancer cells, experts told STAT.
Recent studies have shown that CAR-T cells were superior to autologous transplant in many lymphomas, including follicular and large B cell lymphoma. In just the last year, two clinical trials showed that autologous transplant also had no benefit to mantle cell lymphoma patients who had gone into a first, deep remission after initial therapy thanks to either immunotherapies like CAR-T cells or targeted therapies. That's pushed many lymphoma physicians away from autologous transplant for certain patients.
"We're truly getting away from it," said Elise Chong, a hematologist-oncologist and researcher at the University of Pennsylvania. "For some patients, it may still be appropriate, but the total number we're offering is significantly lower. It's definitely progress."
Autologous transplants have also dropped for multiple myeloma, but only a little, according to data from the Center for International Blood & Marrow Transplant Research. Autologous transplants are still very commonly performed for myeloma, but that may change if ongoing trials studying CAR-T in myeloma show that it's superior to transplant, said Irene Ghobrial, a multiple myeloma physician and researcher at the Dana-Farber Cancer Institute.
"It's another big debate. We will get to know if the CAR-T trial is positive or not, probably in the next few years. But that may change for the first time to say we should not transplant our patients," she said. "But currently, autologous transplant is still the standard of care in myeloma."
The story for allogeneic transplants is also slightly different, said NMDP's Devine. There are some cancer types where allogeneic transplant has faded from use -- particularly certain chronic diseases like chronic lymphocytic leukemia and chronic myeloid leukemia (CML). "CML is the big example. It used to be the most common indication for allogeneic until the late '90s. Then Gleevec came, and now we do two to three hundred transplants for CML in the U.S.," 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 like acute myeloid leukemia. Allogeneic transplants have also become safer over the years, Devine added, making it possible to perform on older patients and to do more transplants with unmatched donors without sacrificing efficacy or safety. "Allogeneic transplants, in our operational data, has been growing about 7-8% per year," Devine said. "What's really been fueling that is the growth in mismatched, unrelated transplants. That's been taking off."
Researchers are working on finding ways to make CAR-T and other novel therapies effective in myeloid malignancies like acute myeloid leukemia, which might one day lead to a reduction in transplantation in these cancers as well. Still, Devine said that despite all the progress over the last 10 years, 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 completely going away."