Long-term follow-up of pediatric patients with EBV-related post-transplant lymphoproliferative disorder

Gałązka, Przemysław; Szafrańska, Małgorzata; Jaremek, Kamila; Rutkowska, Dorota; Czyżewski, K; Dębski, Robert; Richert-Przygońska, Monika; Grzybowski, Tomasz; Konieczek, Joanna; Styczyński, Jan

doi:10.5603/ahp.a2021.0099

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…The standard of care first-line therapy is the use of rituximab (4). Patients who fail first line therapy, should be classified as rituximab-resistant EBV-PTLD.…”

Section: Results Of Therapy Of Ebv-ptldmentioning

confidence: 99%

Management of Resistant Post-transplant Lymphoproliferative Disorder: CAR-T Is a New Option

et al. 2022

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This is a review of the therapeutic options for resistant/refractory post-transplant lymphoproliferative disorder (PTLD) in relation to Chimeric antigen receptor-T cell (CAR-T) therapy. Out of a number of possible future strategies for the treatment of PTLD, the following methods were implemented in real-world practice: anti-PD1 therapy with checkpoint inhibitor nivolumab, new anti-CD20 ofatumumab, brentuximab vedotin, and zanubrutinib. However, for all these innovative methods, only individual cases of successful treatment of rituximabresistant Epstein-Barr Virus (EBV)-PTLD patients have been reported so far. CAR-T is an innovative method of treatment, based on genetic modification of receptors of T autologous lymphocytes, creating the "living drug". This therapy can be potent against resistant PTLD, which is a lymphoproliferation of B-lymphocytes. The published real-world data of 17 patients treated with CAR-T for PTLD indicate a success rate of 76.5%. There is development of innovative methods of treatment of resistant/refractory PTLD, with high rate of resolution after CAR-T therapy.Post-transplant lymphoproliferative disorder (PTLD) is defined as uncontrolled proliferation of B-lymphocytes, occurring after hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT), resulting from iatrogenic suppression of T-lymphocytes (1). In the majority of cases, particularly after HCT, lymphoproliferation is driven by Epstein-Barr Virus (EBV) persisting in a latent form in B-lymphocytes. However, due to impaired function of T-lymphocytes, latent EBV undergoes replication. In the SOT setting, some PTLDs are EBV-negative. EBV-related PTLD can be counted as a secondary malignancy, occurring early after transplantation, usually within the first six months after HCT, and up to several years after organ transplantation. In contrast, EBV-negative PTLD developing >5 years after SOT, should be regarded as a typical non-Hodgkin lymphoma (NHL), being the result of long-term iatrogenic immunosuppression.The objective of this study was to review the therapeutic options for resistant PTLD in relation to the new Chimeric antigen receptor-T cell (CAR-T) treatment.

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“…The standard of care first-line therapy is the use of rituximab (4). Patients who fail first line therapy, should be classified as rituximab-resistant EBV-PTLD.…”

Section: Results Of Therapy Of Ebv-ptldmentioning

confidence: 99%

Management of Resistant Post-transplant Lymphoproliferative Disorder: CAR-T Is a New Option

et al. 2022

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“…12 However, reports of such "late effects" (LE) in PTLD survivors are limited. 13 We sought to characterize LE experienced by SOT recipients with PTLD within our institution to compare toxicity profiles between therapies, so that clinicians can make thoughtful decisions in the management of these patients.…”

Section: Introductionmentioning

confidence: 99%

“…As the number of child, adolescent, and young adult cancer survivors increases, there is growing awareness that these patients may experience significant health difficulties, some of which may be life threatening 12 . However, reports of such “late effects” (LE) in PTLD survivors are limited 13 . We sought to characterize LE experienced by SOT recipients with PTLD within our institution to compare toxicity profiles between therapies, so that clinicians can make thoughtful decisions in the management of these patients.…”

Section: Introductionmentioning

confidence: 99%

Late effects in survivors of post‐transplant lymphoproliferative disease

McGlynn,

Brady,

Healey

et al. 2023

Pediatric Blood & Cancer

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BackgroundTreatment of post‐transplant lymphoproliferative disease (PTLD) varies, with only some patients receiving chemotherapy. Concern for chemotherapy toxicities may influence treatment decisions as little is known regarding the late effects (LE) in PTLD survivors. This report characterizes LE in PTLD survivors at our institution.ProcedurePediatric patients (0–18 years old) diagnosed with PTLD from 1990 to 2020 were examined. All patients included survived 6 months after completing chemotherapy or were 6 months from diagnosis if received no chemotherapy. Treatment with anti‐CD20 antibody (rituximab) alone was not considered chemotherapy. Toxicities were classified per Common Terminology Criteria for Adverse Events Version 5.0. Chi‐square tests assessed differences between categorical groups, or Fischer's exact test or the Fischer–Freeman–Halton exact test for limited sample sizes.ResultsOf the 44 patients included, 24 (55%) were treated with chemotherapy. Twenty‐four (55%) were alive at last follow‐up. Chemotherapy was not associated with differences in survival (odds ratio [OR] 1.40, confidence interval [CI]: 0.42–4.63; p = .31). All patients experienced LE. Grade 3 toxicity or higher was experienced by 82% of patients with no difference in incidence (OR 1.20, CI: 0.27–5.80; p > .99) or median toxicity grade (3.00 vs. 4.00, p = .21) between treatment groups. Patients who received chemotherapy were more likely to experience blood and lymphatic toxicity (58% vs. 25%, p = .03) and cardiac toxicity (46% vs. 15%, p = .03), but less likely to have infections (54% vs. 85%, p = .03).ConclusionsSurvivors of PTLD experience LE including late mortality regardless of chemotherapy exposure. Further investigation to better understand LE could optimize upfront therapy for children with PTLD and improve outcomes.

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Prevalence, management, and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HCT: survey of Infectious Diseases Working Party EBMT

Styczynski,

Tridello,

Wendel

et al. 2023

Bone Marrow Transplant

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Long-term follow-up of pediatric patients with EBV-related post-transplant lymphoproliferative disorder

Cited by 4 publications

References 7 publications

Management of Resistant Post-transplant Lymphoproliferative Disorder: CAR-T Is a New Option

Management of Resistant Post-transplant Lymphoproliferative Disorder: CAR-T Is a New Option

Late effects in survivors of post‐transplant lymphoproliferative disease

Prevalence, management, and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HCT: survey of Infectious Diseases Working Party EBMT

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