Cytomegalovirus surveillance and prevention in allogeneic bone marrow transplantation: Examination of a preemptive plan of ganciclovir therapy

Abstract

Forty-two cytomegalovirus (CMV)-seropositive allogeneic marrow transplant patients or recipients of CMV-seropositive marrow allografts were entered into a surveillance program to detect and treat CMV infection during the first 120 days posttransplant. CMV infection was detected at a mean time of day 50 in 21/37 (58%) patients who had surveillance cultures. Twelve of 42 (28%) received preemptive ganciclovir treatment for virus isolated from blood (9 patients) or from bronchoalveolar lavage fluid (3 patients), and all had no CMV-associated sequelae. CMV disease was diagnosed in 5 patients (4 with pneumonia), 1 with gastroenteritis) who did not have positive cultures until the onset of their disease. CMV-related mortality was 4/42 (10%). Patients who earlier manifested lung injury or diffuse alveolar hemorrhage (DAH) were significantly predisposed to subsequent CMV pneumonia (P = 0.0013, Fisher's exact test) at a median onset of day 42. Restricted prophylactic use of ganciclovir in such patients may be indicated. Fifty percent of all patients never required ganciclovir during the surveillance period. When compared to a universal prophylaxis program of ganciclovir for the prevention of CMV disease, the use of ganciclovir in a preemptive strategy could avoid unnecessary therapy for a substantial number of patients and earn significant cost-savings.

Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection

“…[17][18][19] Preemptive therapy limits the number of patients exposed to unnecessary treatment. If introduced only after documentation of CMV infection, the use of ganciclovir can be restricted to 50% of high risk patients by culture 20 or as shown in our study to 68% by PCR screening. However, culture-based preemptive therapy was hampered by the failure to detect CMV prior to the onset of CMV disease in 12-13% of patients in spite of weekly monitoring by culture Table 4 Duration of antiviral therapy Ͼ4 weeks as a risk factor for secondary non-viral infections…”

“…Bone Marrow Transplantation assays, 4,5,20 leading to a 10% CMV-related mortality. 20 Earlier therapeutic intervention based on more sensitive assays (PCR, antigenemia) resulted in a significant reduction in the incidence of CMV disease.…”

Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance

“…Viral culture and antigen detection are positive in 7-45% of patients following autologous transplantation. [9][10][11][12][13][14][15]17,18 Detection of CMVDNAemia using PCR is also as high as 42% in these surveillance programs. 15 Although the incidence of CMV detection by these surveillance strategies approaches that observed in the allogeneic setting, the number of patients who actually require treatment is quite small.…”

“…[1][2][3] Recent advances in diagnostic techniques have enabled earlier detection of the virus. 4 Furthermore, the use of ganciclovir as prophylactic, 5,6 pre-emptive, [7][8][9] or definitive therapy 10 has reduced mortality rates. Cytomegalovirus is also a major opportunistic pathogen in the autologous BMT setting although mortality is much lower than in allogeneic BMT recipients.…”

A survey of allogeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy

“…24 More recently, interest has focused on the possibility of pre-emptive therapy with ganciclovir based on screening for early CMV with a sensitive diagnostic test. [25][26][27][28][29][30][31][32][33][34][35][36] Tests used as triggers for pre-emptive therapy have included CMV-DNA by PCR, 29,33,34,36 the pp65 antigenemia assay, 27,30,31,[34][35][36] CMV-DNA by hybrid capture assay (Digene), CMV shell vial or tissue culture, 25,[34][35][36] and bronchoalveolar lavage. 26,28 Advocates of universal ganciclovir prophylaxis cite the benefits of a low rate of CMV pneumonitis.…”