1.
Outcomes for patients with EBV-positive PTLD post-allogeneic HCT after failure of rituximab-containing therapy
Socié, G., Barba, P., Barlev, A., Sanz, J., García-Cadenas, I., Chevallier, P., Fagioli, F., Guzman-Becerra, N., Kumar, D., Ljungman, P., et al
Bone marrow transplantation. 2023
Abstract
Epstein-Barr virus-positive (EBV(+)) post-transplant lymphoproliferative disease (PTLD) is an ultra-rare and aggressive condition that may occur following allogeneic hematopoietic cell transplant (HCT) due to immunosuppression. Approximately half of EBV(+) PTLD cases are relapsed or refractory (R/R) to initial rituximab-containing therapy. There are limited treatment options and no standard of care for patients with R/R EBV(+) PTLD, and little is known about their treatment history and outcomes. We performed a multinational, multicenter, retrospective chart review of patients with R/R EBV(+) PTLD following HCT to describe patients' demographic and disease characteristics, treatment history, and overall survival (OS) from rituximab failure. Among 81 patients who received initial treatment with rituximab as monotherapy (84.0%) or in combination with chemotherapy (16.0%), median time from HCT to PTLD diagnosis was 3.0 months and median OS was 0.7 months. Thirty-six patients received a subsequent line of treatment. The most frequent causes of death were PTLD (56.8%), graft-versus-host disease (13.5%) and treatment-related mortality (10.8%). In multivariate analysis, early PTLD onset and lack of response to initial treatment were associated with mortality. This real-world study demonstrates that the prognosis of patients with R/R EBV(+) PTLD following HCT remains poor, highlighting the urgent unmet medical need in this population.
2.
Survival Outcomes of Allogeneic Hematopoietic Cell Transplants with EBV positive or EBV negative Post Transplant Lymphoproliferative Disorder (PTLD), A CIBMTR Study
Naik, S., Riches, M., Hari, P., Soyoung, K., Chen, M., Bachier, C., Shaughnessy, P., Hill, J., Ljungman, P., Battiwalla, M., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2019;:e13145
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Editor's Choice
Abstract
BACKGROUND Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos), EBV-negative (EBVneg) PTLD is reported; yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos = 222, 83%; EBVneg = 45, 17%) were analyzed. RESULTS Two-hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5 - 95) days versus EBVneg 47 (10 - 70) days, p=0.016]. There was no impact on survival by EBV-status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, p = 0.097]. CONCLUSIONS There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Cases of Post-transplant lymphoproliferative disorder (PTLD) following alloHCT reported to the Center for International Blood and Marrow Transplant Research (n=267).
Intervention
EBV positive cases (n=222).
Comparison
EBV negative cases (n=45).
Outcome
Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5 - 95) days versus EBVneg 47 (10 - 70) days]. There was no impact on survival by EBV-status in multivariable analysis.
3.
Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines
Styczynski, J., van der Velden, W., Fox, C. P., Engelhard, D., de la Camara, R., Cordonnier, C., Ljungman, P., Sixth European Conference on Infections in Leukemia, a joint venture of the Infectious Diseases Working Party of the European Society of Blood, Marrow Transplantation, the Infectious Diseases Group of the European Organization for Research, Treatment of Cancer, the International Immunocompromised Host Society, et al
Haematologica. 2016;101(7):803-11
Abstract
Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.