NEW YORK (Reuters Health) – While late mortality among allogenic bone marrow transplant (BMT) patients has decreased over the past 40 years, the declines seemed to be confined to those who had an early transplant or received bone marrow, a retrospective study shows.
“We report for the first time that late mortality has declined significantly; however, life expectancy is not fully restored,” Dr. Smita Bhatia of the University of Alabama at Birmingham told Reuters Health by email. “Further, the decline in late mortality is limited to transplants performed in childhood as well as in patients where we use bone marrow as the source of stem cells and not peripheral blood.”
“While mortality due to recurrence of primary disease is limited to the initial period, mortality due to post-transplant complications (late infections, new cancers, cardiovascular and pulmonary disease) continues to climb,” she said. “This is the single most important reason for the late mortality – and it is important for clinicians to follow patients closely for extended periods of time (for life) and monitor them for these complications.”
As reported in JAMA Oncology, the authors studied data on 4,741 individuals (median age at BMT, 33; 58% male) who lived two or more years after allogeneic BMT performed in three eras: 1974-1989, 1990-2004, and 2005-2014. Median follow-up after BMT was 12 years.
The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% at 30 years.
In contrast, the incidence of nonrecurrence-related mortality continued to increase, reaching 22.3% at 30 years. The main causes of nonrecurrence-related mortality (30-years cumulative incidence) included infection (10.7%; standardized mortality ratio, 52.0); subsequent malignant neoplasms (7.0%; SMR, 4.8); cardiovascular disease (4.6%; SMR, 4.1); and pulmonary disease (2.7%; SMR, 13.9).
Compared with the general population, relative mortality remained higher at 30 or more years after BMT (SMR, 5.4).
Further, the cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost) overall. The years of life lost were greatest for the youngest survivors (age 10, 21.5 years; 31% reduction in life expectancy) and least for the oldest survivors (age 70. 1 year; 8.4% reduction in life expectancy).
Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio of all-cause mortality declined over the three eras (1990-2004: HR, 0.67; 2005-2014: HR, 0.52), as did years of life lost (1974-1989: 9.9 years (reference); 1990-2004: 6.5 years; and 2005-2014: 4.2 years).
The reduction in late mortality was most evident among individuals who underwent transplantation under the age of 18 (reference: 1974-1989; 1990-2004: HR, 0.62; 2005-2014: HR, 0.30) and those who received bone marrow (reference: 1974-1989; 1990-2004: HR, 0.70; 2005-2014: HR, 0.45).
In a separate model, adjustment for stem cell source also reduced the hazard of mortality (1990- 2004: HR, 0.76; 2005-2014: HR, 0.63). The decrease in late mortality by transplant era was statistically significant only among individuals who received bone marrow (1990-2004: HR, 0.70; 2005-2014: HR, 0.45), not peripheral blood stem cells.
Dr. Bhatia noted, “Future research needs to focus on the factors responsible for the lack of decline in mortality among adults receiving BMT as well as individuals receiving peripheral blood stem cell transplantation.”
Dr. Stuart Seropian of Yale University School of Medicine, coauthor of a related editorial, commented in an email to Reuters Health, “The study is an important reminder to us that the effects of stem cell transplantation are not limited to the first few years after the procedure, but may persist for decades.”
“Physicians need to be aware of the increased incidence of late effects after stem cell transplantation and monitor patients accordingly,” he said. “Referral to a survivorship program associated with a transplant program is an optimal way to monitor patients, although this is not always available. Education of patients and primary care providers so as to develop a long-term monitoring plan is essential.”
SOURCE: https://bit.ly/3tQNSoI and https://bit.ly/3AdCXrm JAMA Oncology, online September 9, 2021.
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