Hughes Michael A, Parisi Michele, Grossman Stuart, Kleinberg Lawrence
Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1423-6. doi: 10.1016/j.ijrobp.2004.12.085.
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.
原发性脑肿瘤患者常长期接受高剂量皮质类固醇治疗，以减轻颅内肿胀并缓解头痛等症状。这种治疗可能导致免疫抑制，使患者面临危及生命的机会性感染风险，如卡氏肺孢子虫肺炎。预防性使用抗生素可能会降低某些类型感染的发生风险。本研究的目的是确定CD4细胞计数降低的发生率，以及放疗期间及放疗后监测CD4细胞计数是否有必要。
在约翰霍普金斯医院，对76例连续新诊断为III级和IV级星形细胞瘤及间变性少突胶质细胞瘤且接受皮质类固醇治疗的患者中的70例进行了放疗期间的CD4细胞计数测量。对最近的25例患者每周进行CD4测量。仅当患者CD4细胞计数降低时，才对磺胺过敏者给予预防性甲氧苄啶 - 磺胺甲恶唑（每周一、三、五口服160 mg/800 mg）或氨苯砜（每日口服100 mg）。23%的患者在手术时植入了卡莫司汀化疗晶片，两组分布均匀。没有患者在放疗期间同时接受任何其他化疗。
70例患者中有17例（24%）的CD4细胞计数降至<200/mm³。对于每周进行CD4细胞计数的25例患者，放疗前所有CD4细胞计数均>450/mm³，但放疗期间25例中有6例（24%）降至<200/mm³。CD4细胞计数<200/mm³的患者在放疗期间住院的可能性显著更高（41%对9%，p<0.01），因感染住院的可能性也更高（23%对4%，p<0.05）。两组的总生存期无显著差异。所有CD4细胞计数降低的患者均接受了预防性抗生素治疗，且没有患者发生卡氏肺孢子虫肺炎。没有患者对抗生素治疗出现严重不良反应。两组之间的类固醇平均剂量、平均最低白细胞计数以及接受Gliadel晶片治疗的患者数量无显著差异。
本研究结果证实了临床印象，即原发性脑癌患者使用高剂量皮质类固醇和放疗足以导致严重免疫抑制，并使这些患者面临危及生命的机会性感染风险。针对有风险患者的预防性抗生素方案可能有助于预防治疗的潜在致命副作用。一项前瞻性研究正在进行，以确定这一发现的频率、深度及预后意义。
