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.

Natural Killer Cells for Therapy of Leukemia

“…Patients experiencing CMV reactivation among 674 allogeneic HSCT recipients were protected from leukemia relapse and experienced superior disease-free survival [24]. Similar findings were reported from a study involving 101 ALL and 42 AML pediatric patients [25]. In these patients, NK cells matured rapidly into cytotoxic CD56 dim KIR+ NKG2A- cells as a result of response to stimulatory signals provided by CMV.…”

Viral reactivations following hematopoietic stem cell transplantation in pediatric patients – A single center 11-year analysis

“…Interestingly, when looking at the 85 patients in our cohort who had received an HSCT for a malignant disease, a tendency towards a lower relapse risk was seen in patients affected by viral infections. Several studies showed similar results for CMV, especially in acute myeloid leukemia (AML) patients [48][49][50], Auger et al for EBV and Nordlander et al for HSV infections [51,52]. The underlying mechanism of this relapse reduction remains unknown.…”

Graft γδ TCR Sequencing Identifies Public Clonotypes Associated with Hematopoietic Stem Cell Transplantation Efficacy in Acute Myeloid Leukemia Patients and Unravels Cytomegalovirus Impact on Repertoire Distribution

“…CMV + grafts showed a high presence of private clonotypes, probably due to TRG reshaping, indicating that the donor CMV status could be associated with AML outcome after HSCT. A beneficial effect of CMV reactivation after HSCT has been recently demonstrated, as several studies reported reduced risk of relapse in AML patients who develop CMV reactivation (55)(56)(57). Additionally, donor CMV positivity alone was also associated with a lower relapse rate after HSCT (58).…”