High Incidence of Cytomegalovirus Reactivation and Diseases Following Reduced-Intensity Cord Blood Transplantation for Adult Patients.

Backgrounds: Although cytomegalovirus (CMV) infection is one of the major complication after allogeneic haematopoietic stem-cell transplantation, there is little information on the incidence and clinical features of CMV infection after reduced-intensity cord blood transplantation (RI-CBT) for Adult Patients.

Patients/methods: We reviewed medical records of 166 patients who received RI-CBT at Toranomon Hospital between January 2002 and December 2005. Fifty Patients were excluded due to early death before engraftment, primary graft failure, and those who CMV antigenemia was not properly monitored. The remaining 116 patients were included in the analysis. Median age of the patients was 52 years (range 17–79). Underlying diseases were AML (n=34), ALL (n=13), MDS(n=15), ATL (n=13), CML (n=5), NHL (n=20), and others (n=16). Ninety-four of those were chemo-refractory, and the other were chemo-sensitive. Conditioning regimens comprised of fludarabine 125 mg/m², melphalan 80 mg/m² and total body irradiation (TBI) of (2–4 Gy)(n=107) and others(n=9). Graft-versus-host disease (GVHD) prophylaxis was cyclosporine (n=59) or tacrolimus (n=57). Median number of total nucleated cells and CD34+ cells was 2.6×10⁶ cells/kg (range, 1.8–4.8), and 0.72×10⁵ cells/kg (range, 0.1–4.4) respectively. HLA disparity was 6/6 (n=2), 5/6 (n=17), 4/6 (n=95), and 3/6 (n=2). All the patients were monitored weekly for CMV-antigenemia and received pre-emptive ganciclovir or foscarnet therapy.

Results: Positive antigenemia was observed in 81 patients (70%) at a median of 34 days (range, 0–87) after RI-CBT. Median of maximal numbers of CMV antigen positive cell was 15 per 50,000 leukocytes (range, 1–848). CMV diseases developed in 22 patients (19%) at a median of 45 days (range, 20–350); enterocolitis (n=20), pneumonia (n=2), and adrenalitis (n=1). CMV-antigenemia remained negative in five patients with enterocolitis, even when CMV disease was diagnosed. Twenty of the 22 patients were improved using ganciclovir or foscarnet with only one recurrence. The other two had fatal outcome from CMV disease. Despite improvement of CMV disease, thirteen of the remaining 20 patients died due to infection (n=6 bacterial sepsis: 4, bacterial pneumonia: 1, gas gangrene:1), GVHD (n=2), disease progression (n=3), and others (n=2). Multivariate analysis revealed that grade II–IV acute GVHD were associated with on increased risk and developing CMV disease (p<0.05).

Discussion: CMV reactivation and diseases develop at high frequency and at early period after RI-CBT. Once the disease has established, many of them had poor prognosis despite effective antiviral therapy. Further preventive strategy, such as development of more sensitive monitoring methods, or better prevention and control of GVHD, are warranted.