Pre-Emptive Treatment with Cidofovir for Cytomegalovirus Antigenemia in Autologous Bone Marrow Recipient and CLL Patients on Therapy with Alemtuzumab.

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in patients who have undergone severe immunosuppressive therapy. Ganciclovir continues to be the first choice for pre-emptive therapy, but it needs multiple intravenous daily administration for three weeks and may cause myelosuppression. Cidofovir is a non myelotoxic nucleotide analogue effective against CMV; its favourable pharmacokinetic profile allows a once-a-week dosing. We reviewed a database on 110 consecutive Autologous Stem Cell Transplant (ASCT) and that of 15 Chronic Lymphocytic Leukemia (CLL) patients treated with alemtuzumab. All patients were virologically monitored by quantification of pp65 antigenemia in peripheral blood. Cytomegalovirus infections were identified respectively, in 13 of 110 (12%) ASCT group and in 10 of 15 (66%) CLL group. Nine out 23 CMV reactivation showed manifestation of the infection. All patients were treated on outpatient basis.

Patients with a positive pp65 assay were treated with cidofovir 5 mg/kg once-a-week for two weeks followed by one or two doses every two weeks. Twenty-three patients (13 autologus, 10 alemtuzumab) had 23 episodes of CMV-pp65 detection treated with cidofovir. The first positive antigenemia occurred after a median of 36 days from starting treatment (range 5–20) and the median antigenemia level at first appearance was 2 (range 1– 89).

The treatment produced regression of symptoms in all cases and clearance of the virus in 21 (11 post-transplant 84%; 10 post alemtuzumab 100%), stained by CMV antigenemia. Median duration of therapy was 21 days (range 14–30 days) and the time to the first undetectable antigenemia was seven days (range7–28). We did not observe any further CMV reactivations, also in six of the ten patients who restarted treatment with alemtuzumab after the end of pre-emptive therapy. We did not observe any of the side effects potentially related to cidofovir administration: notably, none of the patients experienced renal toxicity, proteinuria, nausea or vomiting, ophthalmological or neurological toxicity. In our experience, pre-emptive therapy of CMV infection with cidofovir is safe and effective. In our opinion it could be considered an interesting alternative to ganciclovir for pre emptive therapy, particularly advantageous for treatment of CLL and ASCT ambulatory patients at low risk of developing CMV disease.