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. 2019 Mar 5;132(5):525-533.
doi: 10.1097/CM9.0000000000000114.

Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia

Qian Sun  1   2 , Li Wang  1   2 , Hua-Yuan Zhu  1   2 , Yi Miao  1   2 , Wei Wu  1   2 , Jin-Hua Liang  1   2 , Lei Cao  1   2 , Yi Xia  1   2 , Jia-Zhu Wu  1   2 , Yan Wang  1   2 , Rong Wang  1   2 , Lei Fan  1   2 , Wei Xu  1   2 , Jian-Yong Li  1   2
Affiliations

Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia

Qian Sun et al. Chin Med J (Engl). .

Abstract

Background: Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.

Methods: This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.

Results: The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.

Conclusion: This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.

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Figures

Figure 1
Figure 1
Kaplan-Meier curves of TTFT, PFS, and OS stratified by ANAs. (A) The median TTFT for patients with positive ANAs was significantly shorter than those with negative ANAs (13 vs. 40 months, P = 0.049). (B) The median PFS for patients showed no difference between ANAs positive or negative groups (56 vs. 75 months, P = 0.988). (C) The median OS for patients with positive ANAs was significantly shorter than those with negative ANAs (54 months vs. not reached, P = 0.017). ANA: Antinuclear antibody; OS: Overall survival; PFS: Progression free survival; TTFT: Time to first treatment.
Figure 2
Figure 2
Positive ANAs improved the ability of TP53 disruption in predicting OS in CLL patients. Curve of ANA plus TP53: AUC: 0.766, SE: 0.0450, 95% CI: 0.697–0.826; curve of TP53 only: AUC: 0.706, SE: 0.0455, 95% CI: 0.634–0.772; curve of ANA only: AUC: 0.595, SE: 0.0416, 95% CI: 0.520–0.668 (ANA + TP53 vs. TP53 only, P = 0.034; ANA + TP53 vs. ANA only, P < 0.001). ANA: Antinuclear antibody; AUC: Area under the curve; CI: Confidence interval; CLL: Chronic lymphocytic leukemia; OS: Overall survival; SE: Standard error.
Figure 3
Figure 3
Kaplan-Meier curves of TTFT, PFS, and OS stratified by 4 CLL-IPI risk grades. CLL-IPI: Chronic lymphocytic leukemia-international prognostic index; OS: Overall survival; PFS: Progression free survival; TTFT: Time to first treatment.
Figure 4
Figure 4
Positive ANAs improved the ability of CLL-IPI in predicting OS in CLL patients. Curve of CLL-PI (containing serum ANAs level): AUC: 0.781, SE: 0.0460, 95% CI: 0.720–0.835; curve of CLL-IPI: AUC: 0.769, SE: 0.0438, 95% CI: 0.707–0.824; curve of ANA only: AUC: 0.583, SE: 0.0396, 95% CI: 0.515–0.650 (CLL-PI vs. CLL-IPI: P = 0.431; CLL-PI vs. ANA only: P < 0.001). ANA: Antinuclear antibody; AUC: Area under the curve; CI: Confidence interval; CLL: Chronic lymphocytic leukemia; IPI: International prognostic index; OS: Overall survival; PI: Prognostic index; SE: Standard error.
Figure 5
Figure 5
Kaplan-Meier curves of TTFT, PFS, and OS stratified by 4 CLL-PI risk grades. CLL: Chronic lymphocytic leukemia; OS: Overall survival; PFS: Progression free survival; PI: Prognostic index; TTFT: time to first treatment.
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