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Background: The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity-modulated radiotherapy (IMRT)., Methods: A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 10 9 /L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS)., Results: Sixty-nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high-grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses., Conclusions: HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)