Cytomegalovirus replication reduces the relapse incidence in patients with acute myeloid leukemia

Elmaagacli, Ahmet H.; Koldehoff, Michael

doi:10.1182/blood-2016-04-713644

Cited by 43 publications

(35 citation statements)

References 25 publications

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“…We also observed that clinical outcomes were poorer when HSCT recipients developed CMV‐I; however, the basis for this effect remains unclear. Recent data suggest that, although CMV‐I may be protective against relapse, particularly in HSCT recipients with AML undergoing myeloablative allogeneic HSCT, this effect is superseded by an increased non‐relapse mortality risk . When analyzed using a robust Markov multi‐state model, accounting for AML and myeloablative conditioning as well as time‐dependent GVHD, we observed that the directionality of the effect of CMV‐I on relapse favored a greater hazard of relapse, although the CI was greater than one.…”

Section: Discussionmentioning

confidence: 75%

“…Recent data suggest that, although CMV-I may be protective against relapse, particularly in HSCT recipients with AML undergoing myeloablative allogeneic HSCT, this effect is superseded by an increased non-relapse mortality risk. 2,4,6,8,9,30 When analyzed using a robust Markov multi-state model, accounting for AML and myeloablative conditioning as well as time-dependent GVHD, we observed that the directionality of the effect of CMV-I on relapse favored a greater hazard of relapse, although the CI was greater than one. Using the same Markov multi-state model to account for the effect of CMV-I on mortality independent of the competing risk of relapse, we noted a plausible association, although again this did not reach statistical significance (lower limit of the CI was 0.9).…”

Section: Discussionmentioning

confidence: 92%

“…For example, some studies have identified CMV‐I as an independent contributor to mortality both in allogeneic and autologous HSCT, while other studies have not confirmed this observation . Similarly, recent studies suggest that CMV‐I may have a protective effect against relapse, but perhaps only in select populations . Finally, as new strategies for CMV management and prevention become available, it will be important to have a firm understanding of the economic impact of CMV‐I in HSCT .…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Similarly, recent studies suggest that CMV-I may have a protective effect against relapse, but perhaps only in select populations. 2,6,8,9 Finally, as new strategies for CMV management and prevention become available, it will be important to have a firm understanding of the economic impact of CMV-I in HSCT. 10,11 In this study, we aimed to describe the clinical and economic impact of CMV-I in an HSCT cohort in which preemptive CMV antiviral treatment was universally administered at first detectable CMV DNAemia.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

Webb

Harrington

Schwartz

et al. 2018

Transplant Infectious Dis

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

Webb

Harrington

Schwartz

et al. 2018

Transplant Infectious Dis

View full text Add to dashboard Cite

show abstract

“…Natural killer, CD8 and gamma/delta T cells have been shown to be stimulated by CMV reactivation and could cross-react with both viruses and leukemic cells. [17] Moreover, a direct CMV's cytotoxic effect had recently been shown against blast cells, inducing apoptosis. [18] However, viral reactivations are still associated with an increased risk of NRM and thus, choosing a donor according to CMV serostatus has now become a dilemma.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

et al. 2016

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Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors. Myeloablative and reduced-intensity conditioning regimen were given to 71 and 65 patients, respectively. Including CMV reactivations, at least 1 viral reactivation was recorded in 76 patients. Viral reactivations were associated with a lower risk of relapse (adjusted HR 0.14; 95% CI 0.07–0.30; P < 0.01), better disease-free survival (aHR 0.29; 95% CI 0.16–0.54; P < 0.01) but higher non relapse mortality. This translated into a better overall survival (aHR 0.44; 95%CI 0.25–0.77; P < 0.01) in patients who experienced viral reactivation. Thus, viral reactivations, including but not limited to CMV reactivation, are associated with a better outcome particularly with regard to the risk of relapse in AML patients undergoing alloSCT. New guidelines regarding the choice of donor according to the CMV serostatus are needed.

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Absence of early HHV‐6 reactivation after cord blood allograft predicts powerful graft‐versus‐tumor effect

et al. 2018

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Approximately 75% of cord blood transplant (CBT) recipients experience human herpes virus-6 (HHV-6) reactivation. Considering the immunomodulatory effects of HHV-6, we hypothesized that early HHV-6 reactivation may influence the risk of relapse of the underlying hematologic malignancy. In 152 CBT recipients with hematological malignancies, we determined the association between HHV-6 reactivation by day +28 and 2-year cumulative incidence of relapse. In univariate analysis, the absence of HHV-6 reactivation (n = 32) was associated with less relapse (26 [18-35]% vs. 7 [0-17]% in groups with vs. without HHV-6 reactivation, respectively; P = .03). This difference was due to a remarkably low relapse incidence among patients without HHV-6 reactivation. In multivariable analysis, the absence of HHV-6 reactivation was associated with less relapse (hazard ratio [95% confidence interval]: 0.2 [0.05-0.9], P = .03). This association was independent of patient-, disease-, and transplant-related characteristics known to influence the risk of relapse. Natural killer cell and T-cell reconstitution at day +28 were similar between patients with vs. without HHV-6 reactivation. Our results suggest that CB allografts not complicated by HHV-6 reactivation by day +28 have a powerful graft-versus-tumor effect. Knowledge about early HHV-6 reactivation may stratify patients at day +28 into low vs. high relapse risk groups.

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Cytomegalovirus replication reduces the relapse incidence in patients with acute myeloid leukemia

Cited by 43 publications

References 25 publications

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

Absence of early HHV‐6 reactivation after cord blood allograft predicts powerful graft‐versus‐tumor effect

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