Haploidentical hematopoietic cell transplant recipient presents with late‐onset Epstein Barr virus‐associated posttransplant lymphoproliferative disorder

Abstract Posttransplant lymphoproliferative disease (PTLD) is a potentially life‐threatening complication of hematopoietic cell transplantation. With improvements in Epstein‐Barr virus (EBV) monitoring and supportive care, PTLD incidence has decreased throughout the history of bone marrow transplantation. It is rare to develop PTLD after the first year following transplant, across all donor categories. In this case, we hope to elucidate details that may have predisposed to this unusual presentation. We present the case of a 55‐year‐old gentleman with acute myeloid leukemia who underwent a haploidentical transplant for consolidation and presented with fatigue, lethargy and presumed septic shock nearly 7 years after transplant.

With improvements in EBV monitoring and supportive care, PTLD incidence has decreased throughout the history of bone marrow transplantation. It is rare to develop PTLD after the first year following transplant, across all donor categories [1]. In this case, we hope to elucidate details that may have predisposed to this unusual presentation.

Case Presentation
We present the case of a 55-year-old gentleman with acute myeloid leukemia (AML) who underwent a haploidentical transplant for consoli-

DISCUSSION
Posttransplant lymphoproliferative disorder affects the immunocompromised hematopoietic cell and solid organ transplant population.
This case was instructive for how late-onset presentations of PTLD, although rare, must be recognized and treated promptly. A literature review was performed for other such cases of late-onset PTLD and modern evidence-based strategies to mitigate incidence of PTLD.

Epidemiology and risk factors
In for GvHD have repeatedly shown a dramatic decrease in incidence of PTLD, with no cases identified within the first 12 months [3][4][5]. This improves upon previously reported incidence of PTLD of between 4% and 8% in patients receiving unrelated donor or haploidentical HCT and ATG prophylaxis with or without selective T cell depletion [4][5][6].  are suggestive [9]. Staging can be completed in accordance with Ann

Establishing the diagnosis
Arbor and/or Lugano classification [8]. As continued improvements in immunosuppressive management and widespread implementation of PTCy, we expect ongoing progress in the reduction of incidence of PTLD.

Patient-specific discussion
In our patient, who had been treated with posttransplantation cyclophosphamide, the late presentation of PTLD is unusual. He presented with typical symptoms, like lethargy, fatigue, and systemic inflammation [2,3,7]. The clear risk factors in his case include his severe immunodeficiency in the posttransplant period, as evidenced by CMV and VZV viremia, helper T cell lymphopenia [6], along with grade II acute GvHD, although chronic GvHD and use of cyclosporine conferred the highest risk for late-onset PTLD in prior studies [5]. The PTLD in this case was suspected within 48 h of admission and empirically treated 5 days after admission. Clinical, serologic and radiologic testing all showed improvement and even complete remission within two cycles of treatment. He appears to be responding well to conventional dose-adjusted R-EPOCH therapy.

CONCLUSION
Recognizing signs and symptoms of PTLD is critical to early diagnosis and management, especially with late presentations. Current strategies like PTCy and weaning immunosuppression have reduced the incidence of PTLD. Future studies about the epidemiology and management of delayed or late-onset PTLD will be needed to guide treatment in these scenarios, although these studies will likely be limited by the rare presentation of such patients. Becker.

CONFLICT OF INTEREST STATEMENT
All the authors declare that they have no relevant conflict of interest to disclose.

FUNDING INFORMATION
The authors received no specific funding for this work.

ETHICS STATEMENT
This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study. No material was reproduced from other sources. Case discussed was not part of a clinical trial

DATA AVAILABILITY STATEMENT
Data cannot be shared openly to protect participant privacy. As this is a case report, data are stored on the City of Hope electronic medical record and would only be available for review by those directly involved in patient care or on a consented future study.