Abstract
BackgroundThe aim of this study is to evaluate the prognostic factors of overall survival (OS) after haematopoietic stem cell transplant (HSCT) in acute lymphoblastic leukaemia (ALL) patients using accelerated failure time (AFT), Cox proportional hazard (PH), and Cox time-varying coefficient models.Methods206 patients were enrolled after HSCH in Shariati Hospital between 1993 and 2007. There was evidence of marked departures from the proportional hazards assumption with two prognostic factors, relapse and chronic graft-versus-host disease (cGVHD) (P < .001). Performance among AFT and Cox's models was assessed using explained variation and goodness of fit methods. Discrimination among the exponential, Weibull, generalized gamma (GG), log-logistic, and lognormal distributions was done using maximum likelihood and Akaike information criteria.ResultsThe 5-year OS was 52% (95%CI: 47.3–56.7). Peak mortality hazard occurred at months 6–7 after HSCT followed by a decreasing trend. In univariate analysis, the data was better fitted by GG distribution than by other distributions. Univariate analysis using GG distribution showed a positive association between OS with acute graft-versus-host disease (aGVHD) (P = .021), no relapse (P < .001), cGVHD (P < .001), neutrophil recovery (P < .001) and platelet recovery (P < .001). Based on Cox PH models; however cGVHD and relapse were the predictive factors of OS (P < .001). Multivariate analysis indicated that, OS is related to relapse (P < .001) and platelet recovery (P = .037), where predictive power of Weibull AFT models was superior to Cox PH model and Cox with time-varying coefficient (R2 = 0.46 for AFT, R2 = .21 for Cox PH and R2 = .34 for Cox time-varying coefficient). Cox-Snell residual shows Weibull AFT fitted to data better than other distributions in multivariate analysis.ConclusionWe concluded that AFT distributions can be a useful tool for recognizing prognostic factors of OS in acute lymphoblastic leukemia patients.
Highlights
The aim of this study is to evaluate the prognostic factors of overall survival (OS) after haematopoietic stem cell transplant (HSCT) in acute lymphoblastic leukaemia (ALL) patients using accelerated failure time (AFT), Cox proportional hazard (PH), and Cox time-varying coefficient models
Identifying prognostic factors of patients' survival time after Hematopoietic stem cell transplant (HSCT) is of importance because it enables the physicians to detect the factors whose changes affect patients' survival time, and helps them to make the best decision about patients' treatment
The role of some of this prognostic factors such as acute graft-versus-host disease(aGVHD), chronic graft-versus-host disease(cGVHD), age, sex are controversial [2,3,4,5,6], for instance aGVHD was reported a significant factor for survival after HSCT [4,6], whereas it was not a predictive factor in other studies[5,7]
Summary
The aim of this study is to evaluate the prognostic factors of overall survival (OS) after haematopoietic stem cell transplant (HSCT) in acute lymphoblastic leukaemia (ALL) patients using accelerated failure time (AFT), Cox proportional hazard (PH), and Cox time-varying coefficient models. The role of some of this prognostic factors such as acute graft-versus-host disease(aGVHD), chronic graft-versus-host disease(cGVHD), age, sex are controversial [2,3,4,5,6], for instance aGVHD was reported a significant factor for survival after HSCT [4,6], whereas it was not a predictive factor in other studies[5,7]. These differences may be due to a methodological issue. A review of survival analysis in cancer journals reveals that only 5% of all studies using the Cox PH model considered the underline assumption[14]
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