Late Mortality Risk Decreases Among Those Who Undergo Allogeneic Blood or Marrow Transplantation at Younger Age

Although the rate of late mortality among patients who received allogeneic blood or marrow transplantation (BMT) has decreased over the last 40 years, the reduction was specific to patients who underwent transplantation at a younger age or those who received a bone marrow transplant, according to results from a cohort study published in JAMA Oncology.

Patients were at an 8.8-fold higher risk for all-cause mortality (95% CI, 8.4-9.3) than the general population. The relative mortality was highest in the 2- to 5-year period following BMT (standardized mortality ratio [SMR], 34.3; 95% CI, 31.7-36.9). Rates subsequently decreased, although there was still a significantly elevated rate at 30 or more years following BMT (SMR, 5.4; 95% CI, 4.0-7.1). Investigators reported that the reduction in late mortality was most notable among those who were 18 years old or younger and underwent transplantation (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; P <.001). Additionally, those who received a bone marrow transplant also had better outcomes in terms of late mortality risk (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR,

0.45; 95% CI, 0.29-0.69; P < .001).

“To our knowledge, this is the first large, multi-institutional study with mature follow-up, inclusion of both adults and children, and use of rigorous methods to evaluate vital status in patients who undergo BMT,” the investigators wrote. “The data showed an improvement in outcomes over 4 decades of allogeneic transplantation among individuals who underwent transplantation at a younger age and those who received bone marrow.”

The main outcomes of this cohort study were all-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Research was conducted across 3 sites, including City of Hope, University of Minnesota, and University of Alabama at Birmingham.

The patient population included 4741 patients who underwent allogeneic BMT between 1974 and 2014 and survived for at least 2 years. The median age for patients at BMT was 33 years (range, 0-75 years) and the majority of patients were male (57.7%). Additionally, most patients were non-Hispanic White (68.2%), and 2204 individuals (46.5%) received a transplant between 2005 and 2014. The median follow-up after BMT was 12 years (range, 2.0-44.0 years). The most common indication was in patients with acute myeloid leukemia (AML; 26.3%).

From 2 to 35 years following BMT, mortality rates exceeded the expected population rates, with specifically greater differences in expected rates between patients with the shortest (2 years post-BMT; 39.4 deaths per 1000 person-years) and longest follow-up (35 years post-BMT; 31.0 deaths per 1000 person-years).

Among those who survived 2 or more years after receiving BMT, patients experienced a decrease in life expectancy by 20.8% or 8.7 years of life lost. These years of life lost were greatest among younger patients (age 10 years; 31% reduction or 21.5 years) and less among older patients (age 70 years; 8.4% reduction or 1 year).

Investigators reported a reduction in life expectancy of more than 25% among several patient groups, including those older than 45 years at BMT, patients who underwent transplant for acute lymphocytic leukemia, those who underwent transplant between the years of 1974 and 1989, patients who underwent transplant with high-risk disease, and those with chronic graft-versus-host disease (GVHD).

Some risk factors associated with 10-year, all-cause late mortality included older age (>45 years) at BMT (HR, 2.37; 95% CI, 1.87-3.01), male sex (HR, 1.24; 95% CI, 1.09-1.42), high-risk disease (HR, 1.44; 95% CI, 1.24-1.67), use of peripheral blood stem cells as the source (HR, 1.30; 95% CI, 1.07-1.58), and chronic GVHD history (HR, 2.11; 95% CI, 1.80- 2.49).

A decrease in the HR of 10-year all-cause mortality across all eras, including 1974 to 1989 and 1990 to 2004 (HR, 0.67; 95% CI, 0.53-0.85), as well as 1990 to 2004 (HR, 0.52; 95% CI, 0.39-0.69) after adjusting for demographic and clinical factors (P <.001).

Cause of death data were available for 83.4% of the population who died, with factors such as recurrence-related mortality (RRM; 40.3%), nonrecurrence-related morbidity (NRM; 57.4%), and external causes (2.3%) included. Investigators reported a 30-year cumulative incidence rate for RRM of 12.2% (95% CI, 11.0%-13.4%).

Moreover, several factors were associated with RRM including male sex (HR, 1.28; 95% CI, 1.05-1.57); older age at BMT (HR, 1.99; 95% CI, 1.40-2.81); key primary diagnoses such as acute lymphoblastic leukemia (ALL; HR, 3.95; 95% CI, 1.66-9.37) and AML (HR, 3.22; 95% CI, 1.37-7.53); high-risk disease (HR, 1.52; 95% CI, 1.21- 1.90); and chronic GVHD (HR, 2.28; 95% CI, 1.76-2.96). Additionally, NRM had a cumulative incidence rate of 22.3% (95% CI, 20.4%-24.3%), with associated factors including older age at BMT (HR, 2.54; 95% CI, 1.77-3.66), ALL diagnosis (HR, 2.24; 95% CI, 1.10-4.56), high-risk disease (HR, 1.37; 95% CI, 1.09-1.72), and chronic GVHD (HR, 2.20; 95% CI, 1.72-2.83) as associated factors.

“There is a need to address the causes of late mortality among the older BMT recipients as well as those who receive [peripheral blood stem cells] to improve outcomes,” the investigators concluded.

Reference

Bhatia S, Dai C, Landier W, et al. Trends in late mortality and life expectancy after allogeneic blood or marrow transplantation over 4 decades: a blood or marrow transplant survivor study report. JAMA Oncol. Published online September 9, 2021. doi:10.1001/jamaoncol.2021.3676