Early human cytomegalovirus reactivation is associated with lower incidence of relapse of myeloproliferative disorders after allogeneic hematopoietic stem cell transplantation

Abstract

Conflicting results have been reported regarding the association between early cytomegalovirus (CMV) reactivation and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This prompted us to evaluate the impact of CMV reactivation on outcomes of 155 consecutive adult patients transplanted in our institution. In our study, CMV reactivation did not affect cumulative incidence (CI) of relapse in patients with lymphoproliferative disorders. However, the CI of relapse in patients with myeloproliferative disorders (AML and MPN) was 37% (95% CI, 21-53) in patients without CMV reactivation as opposed to 17% (95% CI, 9-28) in patients with CMV reactivation (p = 0.03). An important correlation between CMV reactivation and relapse was found in patients with MPN; the CI of relapse was 50% (95% CI, 12-80) in patients without CMV reactivation as opposed to only 7% (95% CI, 0-27) in patients with CMV reactivation (p = 0.02). A substantial reduction of relapse in myeloproliferative disorders associated with CMV reactivation was confirmed by multivariate analysis (HR 2.73; 95% CI, 1.09-6.82, p = 0.03) using time-dependent covariates for high-risk disease, older age, RIC conditioning, ATG, grade II-IV acute, and chronic GVHD. To our knowledge, we are the first to show an association of CMV reactivation with relapse reduction in MPN patients. This putative virus vs myeloproliferation effect warrants further research.

Improved Overall Survival, Relapse-Free-Survival, and Less Graft-vs.-Host-Disease in Patients With High Immune Reconstitution of TCR Gamma Delta Cells 2 Months After Allogeneic Stem Cell Transplantation

“…Two years later, the study by Scheper et al (44) demonstrating how TCR γδ cells are capable of cross-recognizing CMV and leukemia cells lead to the suggestion that Vδ2 negative cells contributed to the link between CMV reactivation and decreased relapse risk. A recent study demonstrated lower incidence of relapse following early CMV reactivation in myeloproliferative disorders (45). However, as the 2016 CIBMTR study (46), we could not demonstrate an impact of CMV on relapse-free survival, which we additionally analyzed in MDS and AML patients separately due to results from the previous study.…”

Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia

“…The protective effect of CMV on acute leukemia relapse may contribute to this result. The protective effect of CMV has been widely discussed with respect to AML and other myeloproliferative disorders . However, this protective effect is mainly observed in AML allo‐HSCT recipients conditioned by myeloablative regimens but not by reduced‐intensity regimens .…”

Adaptive NK cell reconstitution is associated with better clinical outcomes

“…These observations have led to the hypothesis that NK cells with memory or memory-like properties may have enhanced antitumor activity, supported by recent studies demonstrating an association between CMV reactivation and reduced relapse risk after HCT (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, this finding remains controversial (18,19).…”