Cancer Res Treat.  2020 Jan;52(1):189-206. 10.4143/crt.2019.122.

Diabetes Mellitus Is Associated with Inferior Prognosis in Patients with Chronic Lymphocytic Leukemia: A Propensity Score-Matched Analysis

• Gao R
• Man TS
• Liang JH
• Wang L
• Zhu HY
• Wu W
• Fan L
• Li JY
• Yang T
• Xu W

• KMID: 2501213
• DOI: http://doi.org/10.4143/crt.2019.122

Abstract

Purpose
Diabetes mellitus (DM) is associated with elevated cancer risk and poor survival outcome in malignancies. The objective of this study was to evaluate the prognostic value of preexisting DM in chronic lymphocytic leukemia (CLL).
Materials and Methods
Six hundred and thirty-three subjects with newly-diagnosed CLL between 2007 and 2016 were recruited. Propensity score-matched method was performed to balance baseline characteristics and eliminate possible bias. Univariate and multivariate Cox regression analyses screened the independent risk indicators for time-to-first-treatment (TTFT) and cancer-specific survival (CSS) of CLL. Receiver operator characteristic curves and the corresponding areas under the curve assessed the predictive accuracy of CLL–International Prognostic Index (IPI) together with DM.
Results
The results showed that 111 patients had pre-existing DM. In the propensity-matched cohort, DM was correlated with inferior TTFT and CSS in CLL patients, and it was an independent prognostic factor for both CSS and TTFT. Pre-diabetics also shared undesirable prognostic outcome compared with patients with no diabetic tendency, and a positive association between longer diabetic duration and poorer prognosis of CLL was identified. DM as one additional point to CLL-IPI had larger area under the curve compared with CLL-IPI alone in CSS prediction and could improve the prognostic capacity of CLL-IPI.
Conclusion
Pre-existing DM was found to be a valuable prognostic predictor and could help predict life expectancy and build refined prognostication models for CLL.

Keyword

Chronic lymphocytic leukemia; Diabetes mellitus; Prognosis

Figure

• 

  Fig. 1. Kaplan-Meier curves of time-to-first-treatment (TTFT) and cancer-specific survival (CSS) stratified by diabetic status before and after propensity matching. (A) TTFT in unmatched (complete) dataset. (B) CSS in unmatched (complete) dataset. (C) TTFT in propensity score-matched (1:1) dataset. (D) CSS in propensity score-matched (1:1) dataset.

• 

  Fig. 2. Prediabetes, diabetic duration, and hemoglobin A1c (HbA1c) level in relation to chronic lymphocytic leukemia survival before and after propensity matching. (A) Time-to-first-treatment (TTFT) stratified by different diabetic status of diabetes mellitus, pre-diabetes, and no diabetic tendency in unmatched (complete) dataset. (B) Cancer-specific survival (CSS) stratified by different diabetic status in unmatched (complete) dataset. (C) TTFT stratified by different diabetic status in propensity score-matched (PSM) (1:1) dataset. (D) CSS stratified by different diabetic status in PSM (1:1) dataset. (E) TTFT stratified by different diabetic duration in unmatched (complete) dataset. (F) CSS stratified by different diabetic duration in unmatched (complete) dataset. (G) TTFT stratified by different diabetic duration in PSM (1:1) dataset. (H) CSS stratified by different diabetic duration in PSM (1:1) dataset. (I) TTFT stratified by different HbA1c levels in unmatched (complete) dataset. (J) CSS stratified by different HbA1c levels in unmatched (complete) dataset. (K) TTFT stratified by different HbA1c levels in PSM (1:1) dataset. (L) CSS stratified by different HbA1c levels in PSM (1:1) dataset.

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  Fig. 3. Diabetes mellitus (DM) together with chronic lymphocytic leukemia (CLL)–International Prognostic Index (IPI) is a better prognostic index for CLL. (A) The areas under the curve (AUC) comparison between prognostic index including diabetes mellitus (DM-PI), CLL-IPI and DM alone for time-to-first-treatment (TTFT) prediction. (B) The AUC comparison between DM-PI, CLL-IPI, and DM alone for cancer-specific survival (CSS) prediction. (C) Kaplan-Meier curves of TTFT for four different CLL-IPI risk grades. (D) Kaplan-Meier curves of CSS for four different CLL-IPI risk grades. AUC, area under the curve; SE, standard error; 95% CI, 95% confidence interval. (E) Kaplan-Meier curves of TTFT for four different DM-PI risk grades. (F) Kaplan-Meier curves of CSS for four different DM-PI risk grades.

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