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
- 4 August 2011
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 118 (5), 1402-1412
- https://doi.org/10.1182/blood-2010-08-304121
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.Keywords
This publication has 30 references indexed in Scilit:
- Prospective cytomegalovirus monitoring during first‐line chemotherapy in patients with acute myeloid leukemiaJournal of Medical Virology, 2010
- The transfer of adaptive immunity to CMV during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donorBlood, 2009
- Donor and Recipient CMV Serostatus and Outcome of Pediatric Allogeneic HSCT for Acute Leukemia in the Era of CMV-Preemptive TherapyTransplantation and Cellular Therapy, 2009
- Successful Immune Reconstitution Decreases Leukemic Relapse and Improves Survival in Recipients of Unrelated Cord Blood TransplantationTransplantation and Cellular Therapy, 2006
- Donor cytomegalovirus seropositivity and the risk of leukemic relapse after reduced-intensity transplantsEuropean Journal of Haematology, 2006
- Persisting posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus antigen and predicts for increased late relapse and treatment failureTransplantation and Cellular Therapy, 2004
- SIX WEEKS OF CONTINUOUS INTRAVENOUS CYCLOSPORINE AND SHORT-COURSE METHOTREXATE AS PROPHYLAXIS FOR ACUTE GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE MARROW TRANSPLANTATIONTransplantation, 1990
- GRAFT-VERSUS-LEUKAEMIA ACTIVITY ASSOCIATED WITH CYTOMEGALOVIRUS ANTIBODY POSITIVE BONE MARROW DONORS IN ACUTE MYELOID LEUKAEMIAThe Lancet, 1987
- Reduced risk of recurrent leukaemia in bone marrow transplant recipients after cytomegalovirus infectionBritish Journal of Haematology, 1986
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958