Blood Res.  2021 Sep;56(3):184-196. 10.5045/br.2021.2021107.

Development and validation of a comorbidity index for predicting survival outcomes after allogeneic stem cell transplantation in adult patients with acute leukemia: a Korean nationwide cohort study

• Park SS
• Kim HJ
• Kim TY
• Lee Jy
• Lee JH
• Min GJ
• Park S
• Yoon JH
• Lee SE
• Cho BS
• Eom KS
• Kim YJ
• Lee S
• Kim DW

• KMID: 2520612
• DOI: http://doi.org/10.5045/br.2021.2021107

Abstract

Background
Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS).
Methods
A Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort. A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort.
Results
In the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17＜ score ≤0.4), high-risk (0.4＜ score ≤0.55), and very high-risk (score ＞0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P ＜0.001). The developed scoring system yielded discriminatively different 1-year OS rates and 1-year incidence of non-relapse mortality according to the risk group (P =0.085 and P =0.018, respectively). Furthermore, the developed model showed an acceptable performance for predicting 1-year non-relapse mortality with an area under the curve of 0.715.
Conclusion
The newly developed predictive scoring system could be a simple and reliable tool helping clinicians to assess risk of alloSCT in adults with acute leukemia.

Keyword

Comorbidity; Allogeneic; Transplantation; Stem cell; Acute leukemia; Score

Figure

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  Fig. 1 Flow diagram of the con-struction of the development and validation cohorts. Abbreviation: KNHIS, Korean National Health Insurance Service.

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  Fig. 2 Kaplan-Meier analysis to calculate the overall survival rate in the development cohort.

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  Fig. 3 Probability of overall survival (OS) according to (A) decile risk scores and (B) the final risk groups in the development cohort. Using decile risk scores, we classified the patients into 10 groups: rank 1 (score ≤0.17), rank 2 (score, >0.17 and ≤0.26), rank 3 (score, >0.26 and ≤0.4), rank 4 (score, >0.4 and ≤0.55), rank 5 (score, >0.55 and ≤0.68), rank 6 (score, >0.68 and ≤0.81), rank 7 (score, >0.81 and ≤0.91), rank 8 (score, >0.91 and ≤1.08), rank 9 (score, >1.08 and ≤1.21), and rank 10 (>1.21). Based on the 5-year OS rates in each rank group, we then stratified the patients into 4 risk groups. The low-risk group included patients with rank 1; the intermediate-risk group included patients with ranks 2 and 3; the high-risk group included patients with rank 4; and the very high-risk group included patients with ranks 5, 6, 7, 8, 9, and 10. The log-rank test showed significant differences in the OS among the risk groups (P<0.001).

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  Fig. 4 Validation of the developed scoring system in the validation cohort. (A) The 1-year overall survival (OS) rate was divided according to the risk groups (P=0.085). The post-hoc analysis illustrated a better 1-year OS rate in the low- or intermediate-risk groups than that in the high- or very high-risk groups (P=0.018, * is indicated in the Fig. 1A for the pos-hoc analysis). (B) The cumulative incidence of non-relapse mortality (NRM) was significantly divided according to the risk groups (P=0.035), (C) whereas the cumulative incidence of relapse was not significantly different between the 4 risk groups (P=0.349). (D) A receiver operating characteristic curve analysis achieved an area under the curve (AUC) of 0.715 (95% CI, 0.658–0.772) for predicting NRM events 1-year post-allogeneic hematopoietic stem cell transplantation.

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