Life Expectancy Still Lower for Blood or Marrow Transplant Recipients

While late mortality among recipients of allogeneic blood or marrow transplantation (BMT) has decreased over the past 4 decades, life expectancy among these patients remains shorter versus the U.S. population at large, a retrospective cohort study found.

Compared with the general population, transplant patients had an 8.8-fold higher risk for all-cause mortality. Overall, the life expectancy of patients who underwent BMT was 20.8% lower than expected, translating into 8.7 years of life lost, reported Smita Bhatia, MD, MPH, of the Institute for Cancer Outcomes and Survivorship at the University of Alabama in Birmingham, and colleagues.

Relative mortality among transplant patients was highest in the 2- to 5-year period post-BMT (standardized mortality ratio [SMR] 34.3, 95% CI 31.7-36.9) and remained higher than the general population at 30 or more years post-BMT (SMR 5.4, 95% CI 4.0-7.1), they noted in JAMA Oncology.

The cumulative incidence of recurrence-related mortality plateaued at 10 years, and reached 12.2% (95% CI 11.0-13.4) at 30 years after BMT. However, the incidence of nonrecurrence-related mortality continued to rise, reaching 22.3% (95% CI 20.4-24.3) at 30 years.

The most common causes of nonrecurrence-related mortality included infection, subsequent malignant neoplasms, cardiovascular disease, and pulmonary disease.

While transplantation may provide patients with a new lease on life, the study's findings "illustrate the need for stewardship of medical care over a period of decades," wrote Lohith Gowda, MD, and Stuart Seropian, MD, both of Yale University School of Medicine in New Haven, Connecticut, in an accompanying editorial.

Bhatia and colleagues followed 4,741 patients (57.7% men) who lived 2 years or more after BMT that was performed from January 1974 through December 2014 at three different institutions.

Median age at BMT was 33, and the most common indications for transplant were acute myeloid leukemia (26.3%), acute lymphocytic leukemia (17.8%), and chronic myelogenous leukemia (15.1%).

The 30-year overall survival rate was 57.8% for the entire cohort, ranging from 80.6% for patients with severe aplastic anemia, to 52.5% for patients with chronic myelogenous leukemia.

Risk factors associated with recurrence-related mortality included male sex, older age at BMT, key primary diagnoses (acute lymphoblastic leukemia and acute myeloid leukemia), high-risk disease, and chronic graft-vs-host disease (GVHD), while those associated with nonrecurrence-related mortality included older age at BMT, diagnosis of acute lymphoblastic leukemia, high-risk disease, and chronic GVHD.

"Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population," the study authors wrote.

Bhatia and team also evaluated trends in allogeneic BMT performed in three different eras -- 1974-1989, 1990-2004, and 2005-2014 -- based on changes in transplant practices during those time periods.

Compared with 1974-1989, the adjusted 10-year hazard ratio (HR) of all-cause mortality decreased from 1990-2004 (HR 0.67, 95% CI 0.53-0.85) and 2005-2014 (HR 0.52, 95% CI 0.39-0.69). Years of life lost also declined (1974-1989: 9.9 years; 1990-2004: 6.5 years; and 2005-2014: 4.2 years).

Importantly, in an analysis that was stratified by age at BMT and with the 1974-1989 period as a reference point, the decline in late mortality by time period was statistically significant only in patients who underwent transplantation at age <18 (1990-2004: HR 0.62, 95% CI 0.40-0.96; 2005-2014: HR 0.30, 95% CI 0.16-0.54).

"This finding should be underscored, given that the years of life at risk following a high-risk procedure, such as allografting, are highest in younger patients," Gowda and Seropian wrote.

Additionally, an analysis stratified by stem cell source showed that a decline in late mortality by time period was statistically significant only in patients who received bone marrow (1990-2004: HR 0.70, 95% CI 0.54-0.90; 2005-2014: HR 0.45, 95% CI 0.29-0.69).

"Per one estimate, by 2030, a half million posttransplant survivors are expected to be found in the U.S.," the editorialists noted. "Because most patients receive long-term care with primary care clinicians, education of the broader medical community regarding long-term risk factors is vital."

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