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. 2022 May;198(5):448-457.
doi: 10.1007/s00066-021-01855-5. Epub 2021 Oct 6.

Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy

Roberto Mapelli  1 , Chiara Julita  2 , Sofia Paola Bianchi  2 , Nicolò Gallina  2 , Raffaella Lucchini  2 , Martina Midulla  2 , Flavia Puci  2 , Jessica Saddi  2 , Sara Trivellato  3 , Denis Panizza  3 , Elena De Ponti  3 , Stefano Arcangeli  2
Affiliations

Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy

Roberto Mapelli et al. Strahlenther Onkol. 2022 May.

Abstract

Purpose: Our study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion.

Methods: Between 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose-volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0 × 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan-Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses.

Results: A total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5-55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS.

Conclusion: Although iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.

Keywords: Glioblastoma; Immunosuppression; Lymphopenia; Radiotherapy; Temozolomide.

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Conflict of interest statement

R. Mapelli, C. Julita, S. P. Bianchi, N. Gallina, R. Lucchini, M. Midulla, F. Puci, J. Saddi, S. Trivellato, D. Panizza, E. De Ponti and S. Arcangeli declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Lymphocyte count’s variation from baseline to nadir, with the onset of acute lymphopenia (a), lymphocyte count’s variation from baseline to 1‑year follow-up (b). RT radiotherapy, mos months, PLC peripheral lymphocyte count
Fig. 2
Fig. 2
Kaplan–Meier overall survival curves of the entire group of patients (a), according to the presence of AAL at nadir (b), stratified on grades of AAL (p = 0.004, c) and according to the presence of ARL at nadir (d). Log-rank test, p value < 0.05. AAL acute absolute lymphopenia, ARL acute relative lymphopenia, mo month, PLC peripheral lymphocyte count, G0 grade 0 (PLC > 1000 cells/mm3), G1 grade 1 (PLC: 1000–800 cells/mm3), G2 grade 2 (PLC: 800–500 cells/mm3), G3 grade 3 (PLC: 500–200 cells/mm3), G4 grade 4 (PLC < 200 cells/mm3)
See this image and copyright information in PMC

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