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. 2021 Mar 16;21(1):285.
doi: 10.1186/s12885-021-08004-2.

The predictive value of absolute lymphocyte counts on tumor progression and pseudoprogression in patients with glioblastoma

Jing Xi #  1   2 , Bilal Hassan #  3 , Ruth G N Katumba  1 , Karam Khaddour  4 , Akshay Govindan  5   6 , Jingqin Luo  7 , Jiayi Huang  8 , Jian L Campian  9
Affiliations

The predictive value of absolute lymphocyte counts on tumor progression and pseudoprogression in patients with glioblastoma

Jing Xi et al. BMC Cancer. .

Abstract

Background: Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). The objective of this study was to explore whether patients' absolute lymphocyte count (ALC) levels can be utilized to predict true tumor progression and PsP.

Methods: Patients were considered eligible for the study if they had 1) GBM diagnosis, 2) a series of blood cell counts and clinical follow-ups, and 3) tumor progression documented by both MRI and pathology. Data analysis results include descriptive statistics, median (IQR) for continuous variables and count (%) for categorical variables, p values from Wilcoxon rank sum test or Fisher's exact test for comparison, respectively, and Kaplan-Meier analysis for overall survival (OS). OS was defined as the time from patients' second surgery to their time of death or last follow up if patients were still alive.

Results: 78 patients were included in this study. The median age was 56 years. Median ALC dropped 34.5% from baseline 1400 cells/mm3 to 917 cells/mm3 after completion of radiation therapy (RT) and temozolomide (TMZ). All study patients had undergone surgical biopsy upon MRI-documented progression. 37 had true tumor progression (47.44%) and 41 had pseudoprogression (52.56%). ALC before RT/TMZ, post RT/TMZ and at the time of MRI-documented progression did not show significant difference between patients with true progression and PsP. Although not statistically significant, this study found that patients with true progression had worse OS compared to those with PsP (Hazard Ratio [HR] 1.44, 95% CI 0.86-2.43, P = 0.178). This study also found that patients with high ALC (dichotomized by median) post-radiation had longer OS.

Conclusion: Our results indicate that ALC level in GBM patients before or after treatment does not have predictive value for true disease progression or pseudoprogression. Patients with true progression had worse OS compared to those who had pseudoprogression. A larger sample size that includes CD4 cell counts may be needed to evaluate the PsP predictive value of peripheral blood biomarkers.

Keywords: Absolute lymphocyte count; Glioblastoma; Prognosis; Pseudoprogression.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Boxplot of Absolute lymphocyte count (ALC) before concurrent radiation therapy and temozolomide (RT/TMZ), after RT/TMZ, and at the first MRI documented progression
Fig. 2
Fig. 2
ALC Median Curve
Fig. 3
Fig. 3
CD4 and ALC at the same time point are correlated
Fig. 4
Fig. 4
ALC % change post RT and at progression from prior to RT
Fig. 5
Fig. 5
ROC analysis of ALC % change for tumor/non tumor
Fig. 6
Fig. 6
ROC analysis of each of the ALC at before, post RT and at progression
Fig. 7
Fig. 7
Comparison of overall survival between patients with tumor progression and PsP
Fig. 8
Fig. 8
Comparison of overall survival between patients who received GTR versus those who received either Subtotal resection or Biopsy
Fig. 9
Fig. 9
Comparison of overall survival between patients who received GTR versus those who received a Subtotal resection and Biopsy
Fig. 10
Fig. 10
Kaplan Meier Curve of binary ALC (dichotomized by median with number at risk)
See this image and copyright information in PMC

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