Low Peripheral Lymphocyte Count Before Focal Radiotherapy Plus Concomitant Temozolomide Predicts Severe Lymphopenia During Malignant Glioma Treatment

Abstract

Malignant glioma patients treated with the golden standard therapy, focal radiotherapy plus concomitant daily temozolomide (radiotherapy/TMZ), often suffer severe lymphopenia. The frequency of severe lymphopenia and its predictors were analyzed by assessing adverse effects including decrease in white blood cell counts, lymphocyte counts, and neutrocyte counts according to the Common Toxicity Criteria version 3.0 (CTC) in 28 consecutive patients with pathologically verified malignant gliomas treated with radiotherapy/TMZ. Eighty-two percent of the patients suffered one or more adverse effects; lymphopenia (68%) was the most frequent adverse effect, with 32% of patients suffering CTC grade 4 lymphopenia. CTC grade 4 lymphopenia was associated with the incidence of other CTC grade 3 or 4 adverse effects and discontinuance of TMZ. Minimal lymphocyte counts during radiotherapy/TMZ and lymphocyte counts before radiotherapy/TMZ showed close linear correlation by linear regression analysis (p º 0.0001, R 2 ＝ 0.569), and the most important predictor for CTC grade 4 lymphopenia was lymphocyte count before radiotherapy/TMZ less than 1200/ml by multivariate analysis (p º 0.0321, Exp ＝ 13.2). Lymphocyte counts before radiotherapy/TMZ of less than 1200/ml predict severe lymphopenia during radiotherapy/TMZ.

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

“…9 However, in that study, the enrollment was stopped due to an unacceptable frequency of toxicity related to the neoadjuvant chemotherapeutic agents. Clinical use of 6 weeks of continuous TMZ often causes Grade 3 or 4 lymphopenia, 7,11 and this was seen in the present study. Some animal studies have indicated that TMZ may enhance antitumor immunity.…”

Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

“…Recent advances in immunotherapy research have generated excitement in response to the development of new approaches for treatment of this devastating disease (2,3). However, previous studies have shown that both RT and TMZ can lead to significant lymphopenia in high-grade glioma (HGG) patients (4)(5)(6)(7). For example, Hughes et al (6) reported that 24% of HGG patients treated with RT alone developed lymphopenia with CD4 count decreased to <200 cells/mL (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] version 4.0, grade 3 toxicity).…”

“…Two previous studies examined clinical risk factors associated with ASL during RTþTMZ for HGG (4,7). Both studies identified baseline TLC as a significant factor but not sex or age.…”

“…All other abbreviations are as shown in Table 1. study also showed that changes of CD4 count closely correlated with changes in TLC. Ishikawa et al (7) used CTCAE grade 4 toxicity based on TLC as their primary endpoint (7). Of note, neither of those studies analyzed RT dosimetric parameters.…”

Pathological Changes After Autologous Formalin-Fixed Tumor Vaccine Therapy Combined With Temozolomide for Glioblastoma -Three Case Reports-

“…The worst adverse effect was observed during the initial RT/TMZ treatment in the patient with primary GBM (Case 1), as has been observed in our case series in which 82% of malignant glioma patients suffered one or more adverse effects. 8) Only minor adverse effects such as CTC grade 1 skin reaction were observed during the AFTV/TMZ therapy as well as during the adjuvant TMZ. AFTV-related impairment of vital organ functions was not found, supporting the feasibility of the combination of AFTV and TMZ.…”