AFT survival model to capture the rate of aging and age-specific mortality trajectories among first-allogeneic hematopoietic stem cells transplant patients.

Abstract

Accelerated failure time (AFT) model is commonly applied in engineering studies to address the failure rate of a machine. In humans, survival profile of transplant patients is among the rare scenarios whereby AFT is applicable. To date, it is uncertain whether reliable risk estimates and age-specific mortality trajectories have been published using conventional statistics approach. By investigating mortality trajectory, the rate of aging d(log(μ(x)))/dx of Hematopoietic Stem Cells Transplants (HSCTs) patients who had underwent first-allogeneic transplants can be obtained, and to unveil the possibility of elasticity of human aging rate in HSCTs. A modified parametric frailty survival model was introduced to the survival profiles of 11,160 patients who had underwent first-allogeneic HSCTs in the United States between 1995 and 2006; data was shared by Center for International Bone and Marrow Transplant Research. In comparison to stratification, the modification permits two entities in relation to time to be presented; age and calendar time. To consider its application in empirical studies, the data contains arbitrary right-censoring, a statistical condition which is preferred by choice in many transplant studies. The finalized multivariate AFT model was adjusted for clinical and demographic covariates, and age-specific mortality trajectories were presented by donor source and post-transplant time-lapse intervals. Two unexpected findings are presented: i) an inverse J-shaped hazard in unrelated donor-source t≤100-day; ii) convergence of unrelated-related hazard lines in 100-day<t ≤ 365-day suggests maximum manifestation of senescence among survivors. Analyses of long-term survivors (t>365-day) must consider for periodic medical improvements, and transplant year as a standalone time-variable is not sufficient for statistical adjustment in the finalized multivariate model. In relevance to clinical studies, biennial event-history analysis and age-specific mortality trajectories of long-term survivors provide a more relevant intervention audit report for transplant protocols than the popular statistical presentation; i.e. survival probabilities among donor-source.