Emergence of Cytomegalovirus Disease in Patients Receiving Temozolomide: Report of Two Cases and Literature Review

Abstract

Temozolomide chemotherapy has become part of the therapy used to treat glioblastoma multiforme and refractory anaplastic astrocytoma. Temozolomide frequently produces profound lymphopenia. We report 2 cases of cytomegalovirus disease that occurred in patients receiving temozolomide therapy and review 4 additional cases reported in the literature. Narrow monitoring with cytomegalovirus antigenemia assay should be considered for recommendation.

Reactivation of cytomegalovirus following treatment of malignant glioma with temozolomide

“…The incidence and risk factors of temozolomide-induced CMV reactivation, as well as its optimal management, remain unclear. Steroids also causes immunosuppression and the majority of reported cases of opportunistic CMV infection occurred when patients were treated concurrently with temozolomide and steroids [4,[6][7][8][9], including our case. Therefore, treatment with temozolomide in combination with steroids is supposed to be the cause of immunosuppression and subsequent CMV reactivation.…”

“…T-cell dysfunction, treatment with temozolomide is possibly associated with a decline of the immune system and an increased susceptibility to opportunistic infections such as PCP [3,4]. This characteristic immunosuppression also induces CMV reactivation as a rare complication [4,[6][7][8][9]. The incidence and risk factors of temozolomide-induced CMV reactivation, as well as its optimal management, remain unclear.…”

“…At our institution, patients receiving more than 15 mg/day of predonisolone or those with grade 3/4 lymphocytopenia received cotrimoxazole (1 g/day) as prophylaxis for PCP. Previously, three cases of CMV pneumonia that were induced by temozolomide were reported, and lymphocytopenia occurred in all of them [6][7][8]. Two of them experienced only CMV pneumonia, and prophylaxis for PCP with cotrimoxazole had been provided for one of them [7], whereas cotrimoxazole was not mentioned for the other case [6].…”

“…However, severe lymphocytopenia induced by temozolomide causes opportunistic infections, such as pneumocystis pneumonia (PCP) [3,4] or fulminant hepatitis due to the reactivation of the HBV [5]. Temozolomide has also been reported to induce CMV reactivation [4,[6][7][8][9], which is due to lymphocytopenia, and to cause CMV pneumonia [6][7][8], colitis [4,7,9], and transverse myelitis [4].…”

Cytomegalovirus pneumonitis following temozolomide for the treatment of glioblastoma multiforme

“…In addition, there has been a report of two cases of CMV infection associated with TMZ [9]. In this report, 4 additional cases of CMV infection were culled from the literature and 5 of the 6 cases involved TMZ administration with corticosteroids with evidence of CMV pneumonitis in 3 patients.…”