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How I Treat Patients With EBV-Associated Posttransplant Lymphoproliferative Disease

Julie M. Vose, MD, MBA

Chief, Division of Oncology and Hematology
Neumann M. and Mildred E. Harris Professor
Department of Internal Medicine
University of Nebraska Medical Center
Omaha, Nebraska

Julie M. Vose, MD, MBA, has disclosed that she has received funds for research support from Acerta/AstraZeneca, Celgene/Bristol-Myers Squibb, Epizyme, Incyte, Kite, Loxo, Novartis, and Seattle Genetics and consulting fees from AbbVie, Acerta/AstraZeneca, Conjupro, Janssen/Pharmacyclics, Johnson & Johnson, Kite, Morphosis, Oncternal, Roche/Genentech, and Vaniam Group.

View ClinicalThoughts from this Author

Released: December 6, 2021

Epstein-Barr virus (EBV)–associated posttransplant lymphoproliferative disease (EBV+ PTLD) is a rare complication of stem cell transplantation in which EBV-infected B-cells proliferate uncontrollably. PTLD usually happens following an allogeneic stem cell transplant but is also sometimes seen in patients who have received a solid organ transplant. Below, I share my current approach to treating EBV+ PTLD and where I think treatment might be heading.

Clinical Presentation and Diagnosis
As immunosuppressives have improved, lymphoproliferative disorders have become more common, but our ability to recognize them has also increased. The clinical presentation of EBV+ PTLD can be highly variable and can include lymphadenopathy, a diffuse infiltrate in the transplanted organ, pancytopenia, or fevers of unknown origin. Because presentations can differ so much, healthcare professionals should remain cognizant of this and be watching for symptoms.

Regular EBV blood titers are an effective way to screen patients, as a sharp increase in EBV titers is suggestive for EBV+ PTLD. Although most patients are symptomatic when EBV+ PTLD is detected, titer screening may catch PTLD before symptoms develop. Regular EBV titers are also useful in patients with known EBV+ PTLD since a reduction in EBV titers is a measure of treatment response.

First-line Treatment
The typical first-line treatment for EBV+ PTLD is reducing the immunosuppression for the patient. This is a little tricky because it increases the risk of graft-vs-host disease in patients who have received stem cell transplants and rejection in patients who have received solid organ transplants. If a kidney is rejected, the patient can go back on dialysis while waiting for a new transplant. But if a heart or a lung is rejected, that is difficult to deal with clinically because these are essential organs. So in patients with heart and lung transplants, immunosuppression is not reduced very much.

Treatment of Relapsed Disease
Patients may not respond to the reduction in immunosuppression, so we commonly use rituximab to try to eliminate EBV-infected B-cells. This works, at least temporarily, in many patients and we can monitor EBV titer to determine how effective the treatment is. If rituximab does not work, we may consider chemotherapy.

EBV-specific cytotoxic T-cell therapy is also being evaluated in the relapse setting and is currently in clinical trials. The ongoing, open‑label phase III ALLELE study is evaluating tabelecleucel in patients whose disease is progressing after rituximab or rituximab plus chemotherapy. Patients receive tabelecleucel once weekly for 3 weeks, followed by observation for each 35 day cycle. The first data from the ALLELE trial are being presented at ASH 2021, and this seems like a promising strategy for EBV+ PTLD.

Team Approach to Treatment
The treatment of PTLD requires a team approach with the other healthcare professionals who manage transplant care. In my center, patients who receive allogeneic bone marrow transplants are usually already our patients, which makes things easier. But if a patient has received a solid organ transplant, then we work with whomever manages their organ transplant to balance changes in immunosuppression with other therapies.

Your Thoughts?
What questions do you have on managing patients with EBV+ PTLD?

Do you want to learn more about optimizing the care of patients with EBV+ PTLD? Sign up here to attend the live symposium or simulcast webinar, “A Class in Session: Understanding Current and Future Therapeutic Advances Across B-Cell Lymphomas” on Friday, December 10, 2021, at 7:00 PM Eastern time with me and my colleagues, John P. Leonard, MD, and Brad S. Kahl, MD, when we will discuss the available evidence, key ongoing clinical issues, and new data in various B-cell lymphomas.  

Provided by Clinical Care Options, LLC

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Supported by educational grants from
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BeiGene, Ltd.
Genentech, a member of the Roche Group
Genmab US, Inc.
Incyte Corporation
Karyopharm Therapeutics
Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc.

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