Primary brain tumors treated with steroids and radiotherapy: low CD4 counts and risk of infection

Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted.

CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT.

CD4 counts decreased to <200/mm3 in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm3 before RT, but 6 (24%) of 25 fell to <200/mm3 during RT. Patients with counts <200/mm3 were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of steroids, mean minimal white blood cell count, and number of patients treated with Gliadel wafers were not significantly different between the groups.

The results of this study have confirmed the clinical impression that the use of high-dose corticosteroids and RT in patients with primary brain cancer is sufficient to result in severe immunosuppression and place these patients at risk of life-threatening opportunistic infections. A protocol of prophylactic antibiotics for those at risk may help prevent a potentially fatal side effect of treatment. A prospective study is underway to determine the frequency, depth, and prognostic implications of this finding.