BONE MARROW TRANSPLANT AND LONG TERM MORTALITY RISK

Recipients of donor blood or marrow transplants (BMTs) during childhood remain at increased risk of premature death for 25 years or more after the procedure, researchers say.

"We found that, conditional on surviving the first two years after BMT, the probability of surviving an additional 20 years approached 80%," Dr. Smita Bhatia of the University of Alabama at Birmingham Comprehensive Cancer Center told Reuters Health.

"Overall, the cohort was at a 14-fold greater risk of dying as compared with the general population (of similar age and sex)," she said by email. "Further, this excess risk remained elevated even among those who had survived 25 years."

"On a positive note," she added, "the risk of late mortality has continued to decline over the past three decades."

Dr. Bhatia and colleagues studied 1,388 individuals (about 60% men) who underwent allogeneic BMT at a median age of 14.6 and survived at least two years.

As reported online July 26 in JAMA Oncology, the overall survival rate was 79.9% at 20 years after BMT. Leading causes of death were infection and/or chronic graft-vs-host disease (49.6%); primary disease such as acute lymphoblastic leukemia, acute myeloid leukemia or myelodysplastic syndrome (24.6%); and subsequent malignant neoplasms (18.4%).

As Dr. Bhatia noted, the group had a 14.4-fold increased risk for death compared with the general population and relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9). The absolute excess risk for death from any cause was 12.0 per 1,000 person-years, and the cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up.

Further, the 10-year cumulative incidence of late mortality decreased over time: 18.9% before 1990; 12.8% from 1990-1999; 10.9%, 2000-2010. The decrease remained statistically significant after adjustment for demographic and clinical factors, with hazard ratios compared with the referent group (<1990 0.49="" 0.64="" and="" of="" p="">

"The key practice-changing message," Dr. Bhatia said, "is that there is a need to follow BMT survivors closely long-term and to develop strategies to be vigilant in anticipating and effectively addressing infections several years after BMT, as well as screening for new cancers in this population."

"The long-term risk (of early mortality) is elevated in adults undergoing BMT, as well," she added.

David Loeb, Division Chief of Pediatric Hematology/Oncology and Marrow and Blood Cell Transplantation at the Children's Hospital at Montefiore in New York City, commented, "BMT for children has only been around since the mid-1980s, and so long-term follow-up of the kind described in this study could not have been performed previously. The description of what happens to our patients as they move through adulthood is very important."

The fact that excess mortality has declined over time "probably reflects advances in our ability to perform BMT and manage the toxicities of the procedure over time," he said in an email to Reuters Health.

However, "this study does not compare the experience of patients who had what we now call 'full intensity' or 'myeloablative' transplants and those who had 'reduced intensity conditioning,'" he noted.

"The increased use of less toxic treatment regimens is likely a contributor to the decrease in excess mortality seen in patients transplanted in the 21st century, and as these regimens become even more commonly used, excess mortality should decrease," he said. "We and others are actively working on developing less toxic BMT regimens, and hopefully this will address the concern raised by this paper."

"It is important to recognize that the patients who underwent BMT had immediately life-threatening conditions, and if they had not undergone transplant, would almost all have died," he added. "Thus, the overall survival of this group of patients is better than if none had had a transplant, despite the excess mortality they are experiencing now."

"The long-term toxicities faced by transplant patients, including excess mortality, are important considerations to discuss with potential transplant patients, but this does not mean that transplant is bad - just that we need to continue to work to make the procedure safer, and this information needs to be part of the process of informed consent for the procedure," Dr. Loeb concluded.

SOURCE: http://bit.ly/2OBPFJ8

JAMA Oncol 2018.