Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation

Abstract

PURPOSE Hematopoietic cell transplantation can cure hematologic malignancies and other diseases, but this treatment can also cause late complications. Previous studies have evaluated the cumulative effects of late complications on survival, but longer-term effects on life expectancy after hematopoietic cell transplantation have not been assessed. PATIENTS AND METHODS We used standard methods to evaluate mortality, projected life expectancy, and causes of death in a cohort of 2,574 patients who survived without recurrence of the original disease for at least 5 years after allogeneic or autologous hematopoietic cell transplantation from 1970 through 2002. Sex- and age-specific comparisons were made with US population data. Results Estimated survival of the cohort at 20 years after transplantation was 80.4% (95% CI, 78.1% to 82.6%). During 22,923 person-years of follow-up, 357 deaths occurred. Mortality rates remained four- to nine-fold higher than the expected population rate for at least 30 years after transplantation, yielding an estimated 30% lower life expectancy compared with that in the general population, regardless of current age. In rank order, the leading causes of excess deaths were second malignancies and recurrent disease, followed by infections, chronic graft-versus-host disease, respiratory diseases, and cardiovascular diseases. CONCLUSION Patients who have survived for at least 5 years after hematopoietic cell transplantation without recurrence of the original disease have a high probability of surviving for an additional 15 years, but life expectancy is not fully restored. Further effort is needed to reduce the burden of disease and treatment-related complications in this population.

Fig 1.

Survival and mortality rates for patients younger than age 18 years (solid line), 18 to 45 years (short-dashed line), and older than age 45 years (long-dashed line) at the time of transplantation.

Fig 2.

Mortality rates after transplantation. Empirical mortality rates during each year (solid circles) are shown with fitted rates from the spline-smoothed Poisson regression model (solid line) and associated point-wise 95% CIs (short-dashed line), and the expected mortality rates for each interval based on sex- and age-specific data for the US population in 2001 (long-dashed line).

Fig 3.

Projected reduction in life expectancy in the study cohort relative to US population data as a function of attained age. (A) Absolute reduction in years; (B) percentage reduction.

Fig A1.

Distribution of follow-up according to calendar year. In the article, mortality and life expectancy data for the US population in single-year age intervals are taken from 2001 (black). Cause-specific mortality data for the US population in 5- or 10-year age intervals are taken from 1999 to 2003 (dark blue).

Fig A2.

Mortality ratios for the entire initial cohort of 7,984 patients as a function of time since transplantation. The standardized annual mortality ratios are plotted at the midpoint during each year after hematopoietic cell transplantation at the Fred Hutchinson Cancer Research Center (red circles), with the fitted rates from the spline-smoothed Poisson regression model (gold line) and the associated point-wise 95% confidence limits (blue line). Black points and bars indicate standardized mortality ratios and 95% confidence limits for the cohort reported by Pond et al. The horizontal black line indicates a standardized mortality ratio of 1.0, indicating no excess risk of death compared with sex- and age-specific data for the general population.

Fig A3.

Mortality as a function of age in the study cohort. (A) and (B) Empirical annual mortality rates during each 5-year interval of age, plotted at the midpoint of each interval (black circles), fitted rates from the spline-smoothed Poisson regression model (solid lines) and associated point-wise 95% CIs (short-dashed lines), with projection of model estimates to 100 years of age (gray dashed lines), and the expected mortality rates for each interval based on an average of sex-specific US population rates at each age in 2001 (long-dashed lines), weighted by the overall proportion of follow-up person-years for males and females in the study cohort (53.5% and 46.5%, respectively). Results are shown on log (A) and arithmetic (B) scales. (C) Standardized mortality ratio (the ratio of observed to expected deaths) on a log scale, representing the difference between the two curves in the panel above. The horizontal black line indicates a standardized mortality ratio of 1.0, indicating no excess risk of death compared with the general population. In younger age groups, the standardized mortality ratio is influenced more by changes in expected mortality rates than by changes in the mortality rates of transplantation survivors. (D) Excess deaths per 1,000 person-years of follow-up (the difference between observed and expected deaths), representing the difference between the two curves in the panel above. The number of excess deaths per 1,000 person-years of follow-up is constant in younger age groups and increases in older age groups, because the death rate increases at an earlier age in transplantation survivors than in the US population. Patient groups younger than 10 years of age and older than 70 years of age contained too few events to provide meaningful estimates for comparisons with the US population.

Fig A4.

Mortality ratios and excess deaths among 5-year survivors who had hematopoietic cell transplantation before 18 years of age. Mortality ratios (A and C) and excess deaths per 1,000 person-years (B and D) are shown as a function of time since transplantation (A and B) or attained age (C and D). Empirical annual mortality rates during each 1-year or 5-year interval are plotted at the midpoint of the interval (black circles), with fitted rates from the spline-smoothed Poisson regression model (solid lines) and the associated point-wise 95% CIs (dashed lines). The horizontal black lines indicate a standardized mortality ratio of 1.0, indicating no excess risk of mortality compared with sex- and age-specific data for the general population in 2001. Red circles indicate data from Cardous-Ubbink et al.