Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

Blood. 2011 Aug 4;118(5):1402-12. doi: 10.1182/blood-2010-08-304121. Epub 2011 May 3.

Abstract

The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / complications
  • Down-Regulation
  • Female
  • Graft vs Leukemia Effect / physiology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / therapy*
  • Leukemia, Myeloid, Acute / virology
  • Male
  • Middle Aged
  • Recurrence
  • Risk Factors
  • Time Factors
  • Transplantation, Homologous
  • Virus Replication / physiology*
  • Young Adult