Control EBV to prevent, treat GVHD?
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Donor EBV status affects recipient graft-vs-host disease risk

In allogeneic hematopoietic stem-cell transplantation, the donor’s status regarding Epstein-Barr virus affects the recipient’s risk of developing graft-vs-host disease – a “completely new and striking” finding, according to a report published online April 18 in the Journal of Clinical Oncology.

Approximately 80% of the general population has been infected with EBV and carries persistent virus in memory B cells. When viral material is transmitted to stem-cell recipients, it is known to cause posttransplantation lymphoproliferative disorder. Until now, however, no data were available to examine EBV serology’s effect on other posttransplantation outcomes, said Dr. Jan Styczynski of the department of pediatric hematology and oncology at Nicolaus Copernicus University, Bydgoszcz, Poland, and his associates.

They analyzed information in the European Society of Blood and Marrow Transplantation database for 11,364 patients with acute lymphoblastic leukemia or acute myeloblastic leukemia who underwent stem-cell transplantation between 1997 and 2012 and who were followed for approximately 5 years. Most of the donors (82%) were seropositive for EBV. Acute graft-vs-host disease (GVHD) developed in 32% and chronic GVHD developed in 40% of these stem cell–transplant recipients.

The incidence of chronic GVHD was significantly higher when the donor was EBV-seropositive (41%) than when the donor was EBV-seronegative (31%). Similarly, the incidence of acute GVHD was significantly higher when the donor was EBV-seropositive (32% vs 30%), but the magnitude of the difference between the two groups was smaller. The risk for GVHD increased even though patients receiving transplants from EBV-seropositive donors underwent more intensive GVHD prophylaxis than did those who had seronegative donors, the investigators said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.64.2405).

In contrast, the transplant recipients’ EBV status did not affect their risk of developing GVHD.

“Despite the effect of donor EBV serostatus on GVHD, we did not observe a corresponding GVHD-related death rate, and as a result, there was no effect on overall survival, relapse-free survival, relapse incidence, and nonrelapse mortality. However, it should be kept in mind that many other pre- and posttransplantation factors play a role in contributing to final transplantation outcomes,” Dr. Styczynski and his associates noted.

The current recommendation to monitor transplantation recipients for EBV and to give them “preemptive” rituximab to stave off the development of posttransplantation lymphoproliferative disorder might prove useful in also preventing GVHD, they added.

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The findings of Dr. Styczynski and his associates raise the possibility that we may be able to prevent or treat GVHD in transplant recipients by controlling EBV infection.

Selecting only EBV-negative donors would be one way to accomplish this, but that would be impractical given the high seroprevalence of EBV in the general population. Depleting memory B cells, the reservoir of EBV infection, using monoclonal antibodies may prove helpful, and these agents might provide additional therapeutic effects. And novel antivirals such as retroviral integrase inhibitors may be more specific at targeting EBV than acyclovir and related agents, which have limited activity against latently infected B cells. These novel drugs, however, are not without risks and adverse effects.

A promising alternative might be to boost immunity to EBV using vaccination or adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells.

Dr. Katayoun Rezvani and Dr. Richard E. Champlin are with the University of Texas MD Andersen Cancer Center, Houston. Their financial disclosures are available at www.jco.org. They made these remarks in an editorial accompanying Dr. Styczynski’s report (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2016.66.6099).

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The findings of Dr. Styczynski and his associates raise the possibility that we may be able to prevent or treat GVHD in transplant recipients by controlling EBV infection.

Selecting only EBV-negative donors would be one way to accomplish this, but that would be impractical given the high seroprevalence of EBV in the general population. Depleting memory B cells, the reservoir of EBV infection, using monoclonal antibodies may prove helpful, and these agents might provide additional therapeutic effects. And novel antivirals such as retroviral integrase inhibitors may be more specific at targeting EBV than acyclovir and related agents, which have limited activity against latently infected B cells. These novel drugs, however, are not without risks and adverse effects.

A promising alternative might be to boost immunity to EBV using vaccination or adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells.

Dr. Katayoun Rezvani and Dr. Richard E. Champlin are with the University of Texas MD Andersen Cancer Center, Houston. Their financial disclosures are available at www.jco.org. They made these remarks in an editorial accompanying Dr. Styczynski’s report (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2016.66.6099).

Body

The findings of Dr. Styczynski and his associates raise the possibility that we may be able to prevent or treat GVHD in transplant recipients by controlling EBV infection.

Selecting only EBV-negative donors would be one way to accomplish this, but that would be impractical given the high seroprevalence of EBV in the general population. Depleting memory B cells, the reservoir of EBV infection, using monoclonal antibodies may prove helpful, and these agents might provide additional therapeutic effects. And novel antivirals such as retroviral integrase inhibitors may be more specific at targeting EBV than acyclovir and related agents, which have limited activity against latently infected B cells. These novel drugs, however, are not without risks and adverse effects.

A promising alternative might be to boost immunity to EBV using vaccination or adoptive transfer of ex vivo expanded EBV-specific cytotoxic T cells.

Dr. Katayoun Rezvani and Dr. Richard E. Champlin are with the University of Texas MD Andersen Cancer Center, Houston. Their financial disclosures are available at www.jco.org. They made these remarks in an editorial accompanying Dr. Styczynski’s report (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2016.66.6099).

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Control EBV to prevent, treat GVHD?
Control EBV to prevent, treat GVHD?

In allogeneic hematopoietic stem-cell transplantation, the donor’s status regarding Epstein-Barr virus affects the recipient’s risk of developing graft-vs-host disease – a “completely new and striking” finding, according to a report published online April 18 in the Journal of Clinical Oncology.

Approximately 80% of the general population has been infected with EBV and carries persistent virus in memory B cells. When viral material is transmitted to stem-cell recipients, it is known to cause posttransplantation lymphoproliferative disorder. Until now, however, no data were available to examine EBV serology’s effect on other posttransplantation outcomes, said Dr. Jan Styczynski of the department of pediatric hematology and oncology at Nicolaus Copernicus University, Bydgoszcz, Poland, and his associates.

They analyzed information in the European Society of Blood and Marrow Transplantation database for 11,364 patients with acute lymphoblastic leukemia or acute myeloblastic leukemia who underwent stem-cell transplantation between 1997 and 2012 and who were followed for approximately 5 years. Most of the donors (82%) were seropositive for EBV. Acute graft-vs-host disease (GVHD) developed in 32% and chronic GVHD developed in 40% of these stem cell–transplant recipients.

The incidence of chronic GVHD was significantly higher when the donor was EBV-seropositive (41%) than when the donor was EBV-seronegative (31%). Similarly, the incidence of acute GVHD was significantly higher when the donor was EBV-seropositive (32% vs 30%), but the magnitude of the difference between the two groups was smaller. The risk for GVHD increased even though patients receiving transplants from EBV-seropositive donors underwent more intensive GVHD prophylaxis than did those who had seronegative donors, the investigators said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.64.2405).

In contrast, the transplant recipients’ EBV status did not affect their risk of developing GVHD.

“Despite the effect of donor EBV serostatus on GVHD, we did not observe a corresponding GVHD-related death rate, and as a result, there was no effect on overall survival, relapse-free survival, relapse incidence, and nonrelapse mortality. However, it should be kept in mind that many other pre- and posttransplantation factors play a role in contributing to final transplantation outcomes,” Dr. Styczynski and his associates noted.

The current recommendation to monitor transplantation recipients for EBV and to give them “preemptive” rituximab to stave off the development of posttransplantation lymphoproliferative disorder might prove useful in also preventing GVHD, they added.

In allogeneic hematopoietic stem-cell transplantation, the donor’s status regarding Epstein-Barr virus affects the recipient’s risk of developing graft-vs-host disease – a “completely new and striking” finding, according to a report published online April 18 in the Journal of Clinical Oncology.

Approximately 80% of the general population has been infected with EBV and carries persistent virus in memory B cells. When viral material is transmitted to stem-cell recipients, it is known to cause posttransplantation lymphoproliferative disorder. Until now, however, no data were available to examine EBV serology’s effect on other posttransplantation outcomes, said Dr. Jan Styczynski of the department of pediatric hematology and oncology at Nicolaus Copernicus University, Bydgoszcz, Poland, and his associates.

They analyzed information in the European Society of Blood and Marrow Transplantation database for 11,364 patients with acute lymphoblastic leukemia or acute myeloblastic leukemia who underwent stem-cell transplantation between 1997 and 2012 and who were followed for approximately 5 years. Most of the donors (82%) were seropositive for EBV. Acute graft-vs-host disease (GVHD) developed in 32% and chronic GVHD developed in 40% of these stem cell–transplant recipients.

The incidence of chronic GVHD was significantly higher when the donor was EBV-seropositive (41%) than when the donor was EBV-seronegative (31%). Similarly, the incidence of acute GVHD was significantly higher when the donor was EBV-seropositive (32% vs 30%), but the magnitude of the difference between the two groups was smaller. The risk for GVHD increased even though patients receiving transplants from EBV-seropositive donors underwent more intensive GVHD prophylaxis than did those who had seronegative donors, the investigators said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.64.2405).

In contrast, the transplant recipients’ EBV status did not affect their risk of developing GVHD.

“Despite the effect of donor EBV serostatus on GVHD, we did not observe a corresponding GVHD-related death rate, and as a result, there was no effect on overall survival, relapse-free survival, relapse incidence, and nonrelapse mortality. However, it should be kept in mind that many other pre- and posttransplantation factors play a role in contributing to final transplantation outcomes,” Dr. Styczynski and his associates noted.

The current recommendation to monitor transplantation recipients for EBV and to give them “preemptive” rituximab to stave off the development of posttransplantation lymphoproliferative disorder might prove useful in also preventing GVHD, they added.

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Donor EBV status affects recipient graft-vs-host disease risk
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FROM THE JOURNAL OF CLINICAL ONCOLOGY

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Key clinical point: In allogeneic hematopoietic stem-cell transplantation, the donor’s EBV status affects the recipient’s risk of developing GVHD.

Major finding: Chronic GVHD was significantly more likely to develop when the donor was EBV-seropositive (41%) than EBV-seronegative (31%).

Data source: A retrospective analysis of data regarding 11,364 European patients with acute leukemia who underwent stem-cell transplantation and were followed for 5 years.

Disclosures: No study sponsor was identified. Dr. Styczynski reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.