Despite gains in bone marrow transplant survival, late mortality still a concern, study finds

Research led by UAB’s Institute for Cancer Outcomes and Survivorship and director Smita Bhatia, M.D., MPH (above) finds that patients who received autologous blood or marrow transplantation (using their own cells) over the past three decades lived on average seven years fewer than peers. But newer strategies have narrowed the mortality gap, they report in the Journal of Clinical Oncology.In the decades since blood or marrow transplantation using a patient’s own cells was introduced in 1981, clinicians have known that this lifesaving treatment carries a high risk of late mortality. That is, patients who receive autologous BMT tend to die earlier than their peers, although not necessarily from cancer. Strategies for these procedures have changed over the years, but the impact on mortality rates and life expectancy has been an open question.

It is a growing concern. By 2030, according to one analysis, the number of patients who have received BMT living in the United States will jump fivefold, to more than 500,000 people. Roughly 60 percent of BMT procedures are autologous, based on data recorded between 2015 and 2019 by the U.S. Health Resources and Services Administration, with an average of more than 13,000 autologous BMT procedures each year. Patients receive autologous BMT as a curative treatment for a variety of hematologic malignancies and other conditions, with the most common including multiple myeloma.

Mortality rates decreased, but still higher than general population

In the first large, multi-institutional study to take a comprehensive overview of autologous BMT trends over the past three decades, researchers at the UAB Marnix E. Heersink School of Medicine and two other institutions have tracked outcomes in mortality and life expectancy in more than 4,700 patients who received autologous BMT since 1981.

Mortality rates have decreased over that time, the researchers found; but they are still higher for these transplant recipients than for the general population of the United States. Overall, this excess mortality translates into seven years of life lost by autologous BMT recipients, the researchers report in a paper published online in the Journal of Clinical Oncology on March 9, 2022.

Results highlight need for vigilance

“These results highlight the need for clinicians to be alert for the development of infections, subsequent cancers, and cardiovascular and renal disease in their patients who have had autologous blood or marrow transplantation in order to further reduce late mortality,” said Smita Bhatia, M.D., MPH, senior author of the article, Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades—A BMTSS Report. Bhatia is director of UAB’s Institute for Cancer Outcomes and Survivorship and senior scientist at the O’Neal Comprehensive Cancer Center at UAB.

The research draws on the Bone Marrow Transplant Survivor Study, which includes more than 10,000 patients treated with BMT between 1974 and 2014 at three transplant sites — UAB, the University of Minnesota and City of Hope National Medical Center in California. (The authors of the current article come from each of those three institutions.) The BMTSS is funded by a $6.38 million grant from the National Cancer Institute.

Study details

Transplant strategies have changed significantly over the past decades, the authors point out. Clinicians are now willing to transplant patients at older ages. An increasing proportion of patients have autologous BMT for plasma cell dyscrasias, such as multiple myeloma. The use of total body irradiation has declined, and peripheral blood stem cells are increasingly used as a stem-cell source. The researchers studied 4,702 individuals who lived at least two years following an autologous BMT performed between 1981 and 2014. They divided the time period into four eras: 1981-1999, 2000-2005, 2006-2010 and 2011-2014.

Mortality rates five years after transplant declined over those four eras, with the reduction most pronounced among patients who were transplanted for Hodgkin lymphoma or plasma cell dyscrasias. The researchers did not observe a similar decline in mortality rates among patients transplanted for non-Hodgkin lymphoma or those patients conditioned for BMT with total-body irradiation. The researchers calculated that patients’ average years of life lost following autologous BMT declined from 5.0 years for the earliest era to 1.6 years for the 2011-2014 time period. “Years of life lost were greatest for the youngest survivors (5 years old: 16.5 years of life lost) and smallest for the older survivors (70 years old: 0.6 years),” the authors write.

“Our goal is to find predictive traits for cancer survivors who are at higher risk of long-term problems after treatment in order to help health care providers tailor screenings and other interventions,” Bhatia said.

In addition to Bhatia, authors of Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades—A BMTSS Report include Chen Dai, Wendy Landier, Ph.D., Lindsey Hageman, MPH, Jessica Wu, MPH, Elizabeth Schlichting, MBA, Arianna Siler, Erin Funk, Jessica Hicks, Shawn Lim, Nora Balas and Liton Francisco of the UAB Institute for Cancer Outcomes and Survivorship; Ravi Bhatia, M.D., and Donna Salzman, M.D., of the UAB Division of Hematology, Oncology and Bone Marrow Transplantation; Frederick D. Goldman, M.D., of the UAB Division of Pediatric Hematology, Oncology and Bone Marrow Transplantation; Alysia Bosworth, Stephen J. Forman, M.D., F. Lennie Wong, Ph.D., and Saro H. Armenian, D.O., MPH, of City of Hope; and Hok Sreng Te, Daniel J. Weisdorf, M.D., and Mukta Arora, M.D., of the University of Minnesota.