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Blood stem cell transplantation has been a central player in the treatment of blood cancer for decades. These procedures can improve the patient's survival potential and, in some cases, even provide treatment opportunities. However, over the past decade, doctors say they have begun transplants because of fewer cancer types, particularly lymphoma, and instead have first reached for safer and often more effective new immunity or targeted therapies.
It is an advancement that experts hope to continue. “From my days as a transplant, nothing better than when I didn't have to implant patients,” said Andy Kolb, president and CEO of the Leukemia and Lymphoma Association. “Because it's toxic.”
There are generally two types of stem cell transplants, also known as bone marrow or hematopoietic stem cell transplants: autologous and allografts. The shift from both types of transplants is not even equal from all types of cancer.
Autologous transplantation is when the patient has given a large amount of chemotherapy, then the patient's own stem cells are collected and returned to them. These are commonly used in myeloma, as are many lymphomas. The theory behind autografting was to give patients as much chemotherapy as doctors can clean up cancer, but it would also wipe out the bone marrow of patients where blood stem cells are present. It can make patients more likely to risk things like infections and other complications.
“It's really a sledgehammer type therapy. It's really a high-dose chemotherapy, and it's stem cells just to recover from it,” said Timothy Fenske, a physician and cancer researcher at the University of Wisconsin. “1-3% of patients die from complications as they experience complications. It's not trivial to what people experience.”
Most mantle cell lymphoma patients do not require stem cell transplantation, studies suggest
Another type of stem cell transplant is an allograft in which a healthy donor provides stem cells to a patient. These are most commonly used in certain myeloid malignant tumors, such as acute myeloid leukemia. Chemotherapy is still used in these procedures, but is generally not as intense as autologous transplants.
The idea here is that when a cancer patient is in remission, the healthy immune system from the donor's blood stem cells helps wipe away remaining cancer cells in the patient's body. The opposite side of allografting is that the engrafted immune system may reject a new host and begin attacking the patient. It is a dangerous and sometimes fatal complication known as grafting and host disease.
Experts say that between the two people, autologous transplants has seen a much more dramatic decline than allografts in recent years. “The emergence of technology has ensured that new target small molecules such as tyrosine kinase inhibitors, bispeak and CAR-T have changed the landscape, which are primarily under autograft.”
Mikkael Sequeles, chief of hematology at Sylvester Cancer Center in Miami, said the biggest change was the “Car-T explosion.” CAR-T cell therapy is designed to help patients find and kill cancer cells, experts told STAT.
Recent studies have shown that CAR-T cells are superior to autograft in many lymphomas, including follicles and large B-cell lymphomas. Two clinical trials last year showed that autologous transplantation also had no benefit to mantle cell lymphoma patients who went into initial deep remission after initial treatment, thanks to immunotherapies like CAR-T cells and targeted therapy. This has led many lymphoma physicians to move away from autografting certain patients.
“We're really getting away from that,” said Elise Chong, a hematologist oncologist and researcher at the University of Pennsylvania. “For some patients, that may still be appropriate, but the total number we offer is pretty low. That's definitely an advancement.”
Data from the International Blood and Bone Marrow Transplantation Center shows that autografts have also decreased for multiple myeloma, but only slightly decreased. Irene Ghobrial, a doctor and researcher of multiple myeloma at the Dana-Farber Cancer Institute, shows that continuous trials studying CAR-T in myeloma have shown to be superior to transplants, but autografts are still very common, but that can change.
“That's another big argument. Perhaps in the next few years we can know if the CAR-T trial is positive. But that may be the first time we're saying that patients should not be implanted,” she said. “However, autografting is now the standard care for Mierma.”
The complications and benefits of CAR-T cell therapy are more clear in cancer research “gusts”
The allograft storyline is also slightly different, said Devine of NMDP. There are certain chronic diseases, such as chronic lymphocytic leukemia and chronic myeloid leukemia (CML). “CML is a big example. Previously, it was the most common sign of the same species until the late '90s. Then Gleebeck came and now we're porting 2-300 CML in the US,” Devine says. Gleevec is a targeted therapy for Novartis, used for certain blood and solid cancers.
However, allografting is one of the best options for treating other cancers, such as acute myeloid leukemia. Allografts have also become safer over the years, Devine added, allowing it to be performed in older patients and more implants with unparalleled donors without sacrificing efficacy or safety. “Our operational data shows that allografts increase by about 7-8% per year,” Devine said. “What it really fuels is the growth of unrelated transplants of discrepancies. It's taking off.”
Researchers are working to find ways to make CAR-T and other novel therapies effective in myeloid malignant tumors like acute myeloid leukemia, which could one day lead to a decrease in transplantation of these cancers. Still, Devine said despite all the advances over the past decade, there are still patients who have not recurred or responded to immunotherapy or targeted therapy.
“It's still an important option,” he said. “I don't think the transplant will completely disappear.”
