Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

This corrects the article DOI: 10.1038/leu.2017.9.

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86+pDC frequencies than normal donors (P<0.0024), whereas TFR patients had consistently low CD86+pDC (n=12). This suggested that low CD86+pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6-47.9) for patients with >95 CD86+pDC per 105 lymphocytes, but 70.0% (95% CI 59.3-78.3) for patients with <95 CD86+pDC (hazard ratio (HR) 3.4, 95%-CI: 1.9-6.0; P<0.0001). Moreover, only patients with <95 CD86+pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1-0.8; P=0.0263). High CD86+pDC counts significantly correlated with leukemia-specific CD8+ T-cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21-0.92; P=0.0098). Our data demonstrate that CML patients with high CD86+pDC counts have a higher risk of relapse after TKI discontinuation.

Influence of physical activity on 24-hour measurements of heart rate variability in patients with coronary artery disease.

This study assessed the influence of physical activity on time domain variables of heart rate variability (HRV) during 24-hour electrocardiographic registrations. Changes in time domain variables of HRV (in particular SDNN) obtained from Holter recordings were proven as strong predictors of cardiac events in patients with coronary artery disease. Although 24-hour measurements of HRV recordings are a standard technique, little is known about the effects of the environment during the registration period. This applies especially to the type and nature of physical activity. In a prospective study, 106 patients with angiographically proven coronary artery disease were randomized into 2 groups. Group 1 consisted of 54 patients with recordings under normal daily physical activities. Group 2 consisted of 52 patients who were immobilized during the recording. Both groups were comparable concerning clinical parameters. The results of 24-hour measurements of HRV with analysis of time domain variables (SDNN, SDANN, SDNN index, rMSSD, and pNN50) were compared among the 2 patients groups, and with a healthy control group. Comparison of immobilized patients with healthy controls showed statistically significant differences of all HRV parameters (p <0.01). However, when comparing the activity group with healthy controls, none of the parameters showed any significant differences. Comparison of the subgroups revealed statistically significant differences of the parameters SDNN, SDANN (p <0.01), and borderline results for rMSSD and pNN50 (p = 0.05). Our results indicate that time domain variables of HRV calculated from 24-hour recordings are significantly influenced by the level of physical activity and the upright posture during registration. This methodologic aspect has to be considered, especially if HRV measurements are used as prognostic markers in patients with coronary heart disease.