Reactivation of cytomegalovirus following treatment of malignant glioma with temozolomide

Abstract

Temozolomide is a standard chemotherapeutic agent in the treatment of malignant gliomas. Lymphocytopenia is reported to be the most frequent and severe adverse effect, which causes opportunistic infections such as pneumocystis pneumonia (PCP) and increases the risk of the reactivation of viruses such as hepatitis B virus (HBV) and cytomegalovirus (CMV). However, the incidence of temozolomide-induced CMV reactivation remains unclear. We report on a case of a 62-year-old female with gliomatosis cerebri who had severe lymphocytopenia and pneumonia following concurrent temozolomide treatment and prophylaxis for PCP. She presented cough, fever, and severe lymphocytopenia 1 month after chemoradiotherapy with temozolomide. Her serum b-D-glucan levels remained within the normal range, which was helpful to rule out a diagnosis of PCP. Other opportunistic infections were ruled out, and a blood test for the CMV antigen was positive for pp65 antigenemia. The patient was diagnosed as having CMV pneumonia. She was treated with ganciclovir and recovered. It was very difficult to distinguish between PCP and CMV pneumonia with only the clinical presentation and radiological findings. When a patient receives temozolomide, it is important to be aware of the potential for a CMV reactivation. The serum b-D-glucan levels and pp65 antigenemia are very useful for diagnosis of CMV pneumonia.

Management of Cytomegalovirus Infection in a Patient with Malignant Glioma Treated with Temozolomide and Steroids

“…Therefore, treatment with TMZ in combination with steroids is believed to cause immunosuppression and subsequent CMV reactivation. All previous cases of CMV reactivation associated with TMZ therapy involved lymphocytopenia (ALC range: 0-703 lymphocytes/μL) (6,(10)(11)(12)(13)(14). Our patient also presented with severe lymphocytopenia (ALC: 60 lymphocytes/μL).…”

“…The incidence of TMZ-induced CMV reactivation, its risk factors and its optimal management remain unclear. Steroids also cause immunosuppression, and the majority of reported cases of opportunistic CMV infection, including the present case, have occurred when patients were treated with concurrent TMZ and steroids (6,(10)(11)(12)(13)(14). Therefore, treatment with TMZ in combination with steroids is believed to cause immunosuppression and subsequent CMV reactivation.…”

“…TMZ causes immunosuppression leading to the development of opportunistic infections such as PCP and hepatitis B (8,9). This characteristic immunosuppression can also induce CMV reactivation, a rare complication (6,(10)(11)(12)(13)(14). The incidence of TMZ-induced CMV reactivation, its risk factors and its optimal management remain unclear.…”

“…Narrow monitoring of the lymphocyte and CD4+ T-lymphocyte counts is recommended in patients receiving TMZ and steroids. Physicians should be aware of the possibility for CMV reactivation when the ALC or CD4+ T-lymphocyte count of a patient treated with concurrent TMZ and steroids decreases to approximately 500 lymphocytes/μL (grade 3/4 lymphocytopenia) or 300/μL, respectively (6,(10)(11)(12)(13)(14).…”

“…Severe lymphocytopenia induced by TMZ leads to opportunistic infections such as PCP (6,7) and fulminant hepatitis due to reactivation of the hepatitis B virus (HBV) (8,9). TMZ can also induce cytomegalovirus (CMV) reactivation (6,(10)(11)(12)(13)(14) due to lymphocytopenia and cause CMV pneumonia (11)(12)(13)(14), colitis (6,10,12) and transverse myelitis (6). No reports have yet investigated the resumption of chemotherapy after recovery from CMV reactivation.…”