title: Effect of Cytomegalovirus Reactivation on Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Leukemia.
abstract: Recent studies have demonstrated the protective effect of cytomegalovirus (CMV) reactivation against relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for adult myeloid malignancies. We assessed the association of CMV reactivation, defined as the development of CMV antigenemia (at least 1 pp65 antigen-positive cell per 5.0 × 10(4) WBCs) within 100 days after HSCT, with the risk of relapse in 143 patients with pediatric acute leukemia. The median age at HSCT was 7 years, and underlying diseases included acute lymphoblastic leukemia in 101 patients and acute myeloid leukemia in 42. The cumulative incidence of CMV reactivation at day 100 after HSCT was 45.4%. At a median follow-up of 88 months, patients with CMV reactivation had significantly lower 5-year cumulative incidence of relapse compared with patients without CMV reactivation. In a multivariate analysis, high-level CMV reactivation (≥10 pp65 antigen-positive cells) was an independent factor associated with reduced relapse. However, CMV reactivation was also associated with higher nonrelapse mortality (NRM), mostly caused by opportunistic infection after grades II to IV acute graft-versus-host disease (GVHD), which resulted in decreased probability of survival. High-level CMV reactivation was a risk factor for increased NRM and worse overall survival in multivariate analysis. Although CMV reactivation may reduce the risk of relapse after HSCT for pediatric acute leukemia, effective management of severe acute GVHD and better prophylaxis and treatment of opportunistic infections are required to reduce the incidence of NRM and improve survival. Further studies on pediatric HSCT that include a larger number of patients and more homogenous patient cohorts are desirable.
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan. Electronic address: inagakij@nk-cc.go.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Inagaki
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kurauchi
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanioka
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Reiji
authors.initials: R
authors.lastname: Fukano
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D055815:Young Adult
keywords: CMV reactivation; HSCT; Nonrelapse mortality; Pediatric acute leukemia; Relapse