Expert Consensus on the Characteristics of Patients with Epstein-Barr Virus-Positive Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) for Whom Standard-Dose Chemotherapy May be Inappropriate: A Modified Delphi Study

Adv Ther. 2023 Mar;40(3):1267-1281 doi: 10.1007/s12325-022-02383-z.
Abstract
INTRODUCTION:

Following hematopoietic stem cell transplantation or solid organ transplantation, patients are at risk of developing Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD), which is an ultra-rare and potentially lethal hematologic malignancy. Common treatments for EBV+ PTLD include rituximab alone or combined with chemotherapy. Given specific considerations for this population, including severity of the underlying condition requiring transplant, the rigors of the transplant procedure, as well as risks to the transplanted organ, there is a group of patients with EBV+ PTLD for whom chemotherapy may be inappropriate; however, there is limited information characterizing these patients. This study aimed to reach expert consensus on the key characteristics of patients for whom chemotherapy may be inappropriate in a real-world setting.

METHODS:

A two-round modified Delphi study was conducted to reach consensus among clinicians with expertise treating EBV+ PTLD. Articles identified in a targeted literature review guided the development of round 1 and 2 topics and related statements. The consensus threshold for round 1 statements was 75.0%. If consensus was achieved in round 1, the statement was not discussed further in round 2. The consensus thresholds for round 2 were moderate (62.5-75.0%), strong (87.5%), or complete (100.0%).

RESULTS:

The panel was composed of a total of eight clinicians (seven hematologists/hemato-oncologists) from six European countries. The panel generated a final list of 43 consensus recommendations on the following topics: terminology used to describe patients for whom chemotherapy may be inappropriate; demographic characteristics; organ transplant characteristics; comorbidities that preclude the use of chemotherapy; EBV+ PTLD characteristics; and factors related to treatment-related mortality and morbidity.

CONCLUSIONS:

This modified Delphi panel successfully achieved consensus on key topics and statements that characterized patients with EBV+ PTLD for whom chemotherapy may be inappropriate. These recommendations will inform clinicians and aid in the treatment of EBV+ PTLD.

Metadata
Organisation: Chaganti, Sridhar. Centre for Clinical Haematology, University Hospital Birmingham, Birmingham, UK. Barlev, Arie. Atara Biotherapeutics, South San Francisco, CA, USA. Caillard, Sophie. Department of Nephrology Transplantation, Strasbourg University Hospitals, Strasbourg, France. Choquet, Sylvain. Department of Hematology, Hospitalier Pitie Salpetriere, Paris, France. Cwynarski, Kate. Department of Haematology, University College Hospital, London, UK. Friedetzky, Anke. Atara Biotherapeutics, Zug, Switzerland. Gonzalez-Barca, Eva. Department of Hematology, Institut Catala d'Oncologia, IDIBELL, Universitat de Barcelona, Barcelona, Spain. Sadetsky, Natalia. Atara Biotherapeutics, South San Francisco, CA, USA. Schneeberger, Stefan. Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria. Thirumalai, Dhanalakshmi. Atara Biotherapeutics, 2380 Conejo Spectrum St, Suite 200, Thousand Oaks, CA, 91320, USA. dthirumalai@atarabio.com. Zinzani, Pier L. IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seragnoli", Bologna, Italy. Zinzani, Pier L. Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Universita di Bologna, Bologna, Italy. Trappe, Ralf U. Department of Hematology and Oncology, DIAKO Hospital Bremen, Bremen, Germany.
Funding: Industry funding
Publication type: Guideline
Organ: Various; Kidney; Liver; Heart
Language: English
MeSH terms: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Consensus; Delphi Technique; Lymphoproliferative Disorders; Kidney Transplantation; Liver Transplantation; Heart Transplantation