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Blood and marrow transplantation strategies have changed significantly over the past four decades; but recipients still experience excess mortality that translates into 8.7 years of life lost, according to researchers in UAB’s Institute for Cancer Outcomes and Survivorship.In the first large, multi-institutional study with mature follow-up, researchers at the University of Alabama at Birmingham Marnix E. Heersink School of Medicine and two other institutions have tracked trends in mortality and life expectancy after allogeneic (that is, from a source other than the patient) blood or marrow transplantation (BMT) over four decades. That time period includes three distinct eras marked by changes in how BMT is performed. Mortality rates have decreased over that time, the researchers found; but they are still higher for BMT recipients than the general population of the United States. Overall, this excess mortality translates into 8.7 years of life lost by BMT recipients.
The researchers also identified a previously unreported association between the use of peripheral blood stem cells in BMT and overall mortality risk, as well as risk of infection-related mortality and pulmonary mortality. The research was published online in the journal JAMA Oncology on Sept. 9, 2021.
An estimated 10,000 patients in the United States receive allogeneic BMT annually, according to 2019 data. By 2030, according to one study, there will be a half-million BMT recipients in the United States. Patients receive allogeneic BMT as a curative treatment for a variety of cancers and other conditions, with the most common including leukemias, severe aplastic anemia, lymphomas and other life-threatening illnesses such as immune deficiencies.
“Steady improvements in outcomes have resulted in a growing number of BMT survivors; but this is a population uniquely vulnerable to long-term, life-threatening risk for a variety of conditions,” said Smita Bhatia, M.D., MPH, senior author of the article, Trends in Late Mortality and Life Expectancy After Allogeneic Blood or Marrow Transplantation Over 4 Decades. Bhatia is director of UAB’s Institute for Cancer Outcomes and Survivorship and senior scientist at the O’Neal Comprehensive Cancer Center at UAB. “Previous studies have examined the risk of this ‘late mortality,’ but they have looked at different transplant eras and studied different cohorts of patients. This new study offers a comprehensive picture of key trends in patient outcomes, taking advantage of the largest BMT cohort collected to date.”
“Steady improvements in outcomes have resulted in a growing number of BMT survivors, but this is a population uniquely vulnerable to long-term, life-threatening risk for a variety of conditions. Previous studies have examined the risk of this ‘late mortality,’ but they have looked at different transplant eras and studied different cohorts of patients. This new study offers a comprehensive picture of key trends in patient outcomes, taking advantage of the largest BMT cohort collected to date.”
The current research was made possible by the development of the Bone Marrow Transplant Survivor Study (BMTSS), 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.
The study examined data from a group of more than 4,700 individuals who received allogeneic BMT between Jan. 1, 1974, and Dec. 31, 2014, and lived for two or more years after the procedure.
“Transplant strategies have evolved over the past four decades, with the overarching goal of improving disease control and expanding the population of patients who could benefit from BMT,” the authors write. “In particular, there is an increase in age at BMT in patients receiving transplants from donors other than human leukocyte antigen-matched siblings and in the use of peripheral blood stem cells as a stem cell source. There is also an increase in the use of reduced-intensity conditioning.”
Taking these evolving transplant strategies into account, the authors continue, they observed a decrease in mortality rates from all causes between the earliest era (1974-1989) and the latest era (2005-2014). The reduction in risk was most pronounced among patients who underwent transplantation when younger than 18 years and those who received bone marrow as a stem cell source. “There was no meaningful decrease in mortality among patients who underwent transplantation at older ages or those who received peripheral blood stem cells,” they write.
Smita Bhatia, M.D., MPH“The reduced life expectancy among BMT recipients could be a result of the cumulative effects of pre-transplant and transplant-related therapeutic exposures as well as post-transplant events, such as chronic graft-versus-host disease, infections, subsequent cancers, cardiovascular disease and pulmonary disease,” Bhatia said.
In an accompanying editorial , Lohith Gowda, M.D., and Stuart Seropian, M.D., of Yale Comprehensive Cancer Center at Yale University, noted that the study had many important findings, including highlighting the substantial burden of mortality from issues not related to cancer recurrence, especially cardiopulmonary events. (These include congestive heart failure and coronary artery disease.) “Survivorship issues for adults in the modern era will require specialists, ideally with expertise in the intersection of geriatrics and transplantation,” Gowda and Seropian write.
Bhatia agrees. “Our institute is particularly interested in identifying predictive traits of cancer survivors at higher risk for long-term problems that could enable health care providers to tailor screenings and other interventions to these populations,” she said. “The overarching goal of our research is to reduce the burden of mortality carried by cancer survivors and improve their quality of life.”
In addition to Bhatia, authors of Trends in Late Mortality and Life Expectancy After Allogeneic Blood or Marrow Transplantation Over 4 Decades include Chen Dai, Wendy Landier, Ph.D., Lindsey Hageman, MPH, Jessica Wu, MPH, Elizabeth Schlichting, MBA, Arianna Siler, Erin Funk, Jessica Hicks 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.