Henry Chi Hang Fung, MD, FACP, FRCPE
Nearly 50 years after the first successful bone-marrow transplant to treat leukemia, the number of hematopoietic stem cell transplants (SCTs) performed annually continues to increase. Growth will continue in the coming years, predict experts in the field.
Transplants have become increasingly easy to perform, as research advances have broadened the pool of cell donors and reduced or eliminated graft-versus-host disease (GVHD) in more patients. Less intensive minitransplants and improvements in supportive care have opened up SCT to older recipients, particularly patients aged between 60 and 69 years. Although chimeric antigen receptor (CAR) T-cell therapies and many new drugs for blood cancers have emerged in recent years, these therapies are often used in conjunction with traditional transplants rather than supplanting them.
Broadly defined, cell transplant for cancer is poised to become only more common, said Henry Chi Hang Fung, MD, FACP, FRCPE, director of the Fox Chase–Temple University Hospital Bone Marrow Transplant Program in Philadelphia, Pennsylvania.
Questions about the future of cell transplantation programs “have been asked over the past 30 or 40 years, and transplant is still here,” Fung said. “The field has evolved rapidly. For example, the cellular therapies—CAR T-cells or engineered T-cells—are rapidly expanding, and they’re always done by transplant programs. FDA will only let transplant people do them. Transplant will be rapidly expanding, depending on how you define it.”
Expanded Donor-Cell Options
Traditional SCT falls into 2 categories: autologous and allogeneic. In the autologous variety, a patient’s blood-forming stem cells are collected, chemotherapy is administered, and the cells are reinfused into the patient. Autologous SCT is a standard treatment for multiple myeloma (MM), which accounts for the largest number of transplants overall. Autologous is also the predominant type used to treat non-Hodgkin lymphoma (NHL) and Hodgkin disease.1
In allogeneic transplant, the patient receives cells from a matching donor after undergoing a conditioning therapy, typically total body irradiation with or without chemotherapy. Allogeneic is used most often for acute myeloid leukemia (AML), as well as for myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), acute lymphocytic leukemia (ALL), and NHL.
To avoid GVHD and transplant failure, successful allogenetic transplants once required cell donation from an identical sibling or from a relative or unrelated donor who was a close human leukocyte antigen (HLA) match. In the early 2000s, researchers at Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, found they could make half-matched cell donations work by giving high doses of the chemotherapy drug cyclophosphamide (Cytoxan) after a transplant. The drug killed off donor cells that would have attacked the patient while leaving intact the regulatory T cells that helped rebuild the recipient’s immune system.
Cyclophosphamide therapy al lowed greatly expanded use of donations from 50% HLA-matched family members and was widely adopted, contributing to a surge in such transplants since 2012 (Figure 1
“Probably the biggest change in the last 5 years has been the use of half-matched donors or haploidentical stem cell transplant,” said John F. DiPersio, MD, PhD, a professor at Washington University School of Medicine in St. Louis, Missouri. “They’ve emerged onto the scene robustly and the numbers of haplo transplants are increasing. Most studies show that the outcomes are fairly similar to unrelated donor transplants. Now it’s conceivable that you can find a donor for nearly everyone, which was not the case in the past. We’ve seen this emerge and the growth of unrelated donor transplants has slowed.”
Figure 1. Allogeneic SCT Recipients in the United States by Donor Type1
Trends in Stem Cell Sources
An earlier major innovation in the 1980s and 1990s was the development of methods to harvest stem cells from blood rather than bone marrow. Peripheral blood stem cell (PBSC) transplantation is now standard in autologous transplant and is used in more than 75% of allogeneic SCTs.2
PBSCs are easier to collect and produce faster engraftment, although they are associated with higher rates of chronic GVHD, which is of particular concern for pediatric patients who will live for many decades after treatment.
Bone marrow cells are still often used in patients aged under 18 years, accounting for half of the unrelated-donor transplants in that group, according to data from the Center for International Blood and Marrow Transplant Research (CIBMTR).