title: 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.
authors.affiliation: Haematology, Westmead Hospital, Westmead, New South Wales, Australia. biju.george@swahs.health.nsw.gov.au
authors.forename: B
authors.initials: B
authors.lastname: George
authors.forename: N
authors.initials: N
authors.lastname: Pati
authors.forename: N
authors.initials: N
authors.lastname: Gilroy
authors.forename: M
authors.initials: M
authors.lastname: Ratnamohan
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.forename: I
authors.initials: I
authors.lastname: Kerridge
authors.forename: M
authors.initials: M
authors.lastname: Hertzberg
authors.forename: D
authors.initials: D
authors.lastname: Gottlieb
authors.forename: K
authors.initials: K
authors.lastname: Bradstock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018890:Chemoprevention; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014775:Virus Activation; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents