Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy

Abstract

Between January 2001 and June 2008, 315 adult patients (median age 43 years, range 16-65) including 203 males and 112 females undergoing hematopoietic stem cell transplantation (HSCT) had serial monitoring for cytomegalovirus (CMV) followed by initiation of preemptive therapy. The majority (62.1%) had a conventional myeloablative transplant with 116 (36.9%) having a reduced-intensity conditioning (RIC) transplant, using either matched sibling/family (63.3%) or unrelated donors (36.7%). Graft source was peripheral blood stem cells in 257 (81.5%), bone marrow in 41 (13.1%), and cord blood in 16 (5.4%). T-cell depletion with anti-thymocyte globulin or alemtuzumab was used in 35%. Based upon CMV serostatus, patients were classified into low risk (donor [D]-/recipient [R]-), intermediate risk (D+/R-), or high risk (D-/R+ or D+/R+). Serial weekly monitoring for CMV viremia was performed using a qualitative polymerase chain reaction (PCR) and when positive, quantification was done using either pp65 antigen or a quantitative PCR. CMV reactivation was seen in 123 patients (39.1%) at a median of 50 days post HSCT (range 22-1978). CMV serostatus was the most important risk factor with incidence of 53% in the high-risk group (53.3%) compared with 10.2% in the intermediate risk and 0% in the low-risk group (P<0.0001). Other significant risk factors identified included use of alemtuzumab during conditioning (P=0.03), RIC transplants (P=0.06), and the presence of acute graft-versus-host disease (GVHD) (P<0.0001). On a multivariate analysis, CMV serostatus, RIC transplants, and acute GVHD remained independent predictors of CMV reactivation. All were treated with antiviral therapy with responses seen in 109 (88.6%). Sixteen patients (13%) developed CMV disease at a median of 59 days post HSCT (range 26 days-46 months), 8 of whom died. At a median follow up of 43 months (range 6-93), 166 patients (52.6%) are alive with a significantly higher survival among patients without CMV reactivation (57.2%) as compared with patients with CMV reactivation (45.5%; P=0.049). CMV reactivation and disease remains a major problem in high-risk patients undergoing allogeneic HSCT. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this specific group of patients.