Valganciclovir thrice weekly for prophylaxis against cytomegalovirus reactivation during alemtuzumab therapy

The monoclonal anti-CD52 antibody alemtuzumab is active against chronic lymphocytic leukemia and other low-grade B- and T-cell lymphoproliferative diseases. It is lymphoablative, making patients susceptible to opportunistic infections. Reactivation of cytomegalovirus (CMV) infection occurs in 10–100% of cases, depending on the patient population, the frequency and the sensitivity of the virologic surveillance tests employed.1 Until lately, relatively ineffective drugs including acyclovir, valaciclovir or famciclovir have been used as CMV prophylaxis.2 Recently, it has been reported that valganciclovir at 450 mg twice daily prevented CMV reactivation.3 In an earlier study, we found CMV reactivation in all 10 patients given alemtuzumab.1 An update of this series of 12 patients (Supplementary file 1), given acyclovir or valaciclovir prophylaxis, showed CMV reactivation in all of them, as evidenced by positive PCR and pp65 antigenemia. There was one fatality due to CMV pneumonitis. From 2005 onward, valganciclovir prophylaxis was administered to all patients given alemtuzumab. There were 18 Chinese patients (Supplementary file 2) who received a median dose of 300 mg (30–1800) of alemtuzumab. Valganciclovir prophylaxis was 900 mg daily three times per week in 16 patients, 900 mg daily two times per week in one patient and 900 mg daily in one patient, from the commencement of alemtuzumab to 2 months after treatment cessation. CMV status was monitored by weekly PCR and pp65 antigen assay.1 Severe lymphopenia (median nadir lymphocyte count: 0 (0–0.9) 109 per l) developed in 17 patients. In the only case without lymphopenia, nearly all the lymphocytes were large granular lymphocyte leukemia cells. Neutropenia (<1 109 per l) developed in four cases. In two patients, neutropenia was related to the underlying diseases (stage IV chronic lymphocytic leukemia and CD4+CD56+ hematodermic malignancy), and valganciclovir was continued. In two patients, neutropenia occurred about 2 weeks after concomitant chemotherapy and blood counts recovered after cessation of valganciclovir. During valganciclovir prophylaxis, no patients developed CMV reactivation. Sixteen patients completed valganciclovir prophylaxis without CMV reactivation. Prophylaxis was interrupted in two cases, because of neutropenia and pneumonia. CMV reactivation occurred 1 and 6 weeks later. Both responded to foscarnet and valganciclovir/ganciclovir treatment. Our results showed that valganciclovir 900 mg three times weekly successfully prevented CMV reactivation. We used PCR to exclude CMV reactivation,1 underlining the effectiveness of our regimen in preventing even minute degrees of CMV reactivation. Furthermore, among various racial groups, Asian patients have the highest incidence of CMV reactivation after chemotherapy and hematopoietic stem cell transplantation.4 Even in this high-risk group, our regimen totally prevented CMV reactivation. Valganciclovir is expensive and potentially myelosuppressive. Valganciclovir 900 mg three times per week entails much cost saving and a reduced risk of neutropenia as compared with a daily regimen as reported.3 YY Hwang treated the patients, analyzed the data, wrote and approved the paper. WWW Cheung treated the patients, analyzed the data and approved the paper. AYH Leung, E Tse and WY Au treated the patients and approved the paper. YL Kwong designed the study, treated the patients, wrote and approved the paper. Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)