Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud; Hamilton-Dutoit, Stephen; Andersen, Claus Yding; Møller, Michael; Sørensen, Søren Schwartz; Jespersen, Bente; Kampmann, Jan; Søndergård, Esben; Nielsen, Patricia Switten; d’Amore, Francesco

doi:10.3109/10428194.2014.966242

Cited by 33 publications

(27 citation statements)

References 27 publications

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“…The early occurrence is in accordance with its higher risk in the first year after solid organ transplantation [12]. This type of PTLD may be CD30+ [13], theoretically with potential therapeutic implications [14]. …”

Section: Discussionmentioning

confidence: 72%

Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Montpréville

Pavec²,

Ladurie³

et al. 2015

Respiration

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Background: The incidence of posttransplant lymphoproliferative disorders (PTLD) has recently declined, but late cases are increasingly reported in lung transplant recipients. Objectives: We present our experience with PTLD after lung transplantation, attempting to examine the distinguishing characteristics of early versus late cases. Methods: We have reviewed clinical and pathological data of all cases occurring in our institution between 2001 and 2014. Results: Patients, aged 15-63 years, were mostly (12/16) Epstein-Barr virus (EBV) seropositive at the time of transplantation. Eleven early cases, occurring 9.4 ± 5.2 months after transplantation and mostly (9/11) prior to 2010, had EBV+ diffuse large B-cell lymphomas. Lungs and/or thoracic lymph nodes were often involved (n = 8). Treatments included reduction of immune suppression (n = 11), rituximab (n = 8) and chemotherapy (n = 7). Two patients are in complete remission at 26 and 216 months. Nine patients died 8.0 ± 6.5 months after PTLD diagnosis. Of the 5 cases with late PTLD occurring 4-23 years (mean ± SD: 10.4 ± 7.7) after transplantation (and 3/5 after 2009), 1 had pulmonary lymphomatoid granulomatosis (only endothoracic case), 1 cutaneous large T-cell lymphoma, 2 had anaplastic large cell lymphomas, and 1 Hodgkin's disease. Two of the 5 cases were EBV-, including one followed by a second EBV+ PTLD after 8 years of complete remission. Two patients were alive and well (follow-up: 44 and 151 months), one having suffered from EBV-related cholestatic hepatitis 6 years after the PTLD. Conclusion: Our small experience shows a trend toward (very) late occurrence, associated with more unusual clinicopathologic features, but not with a worse prognosis.

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Section: Discussionmentioning

confidence: 72%

Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Montpréville

Pavec²,

Ladurie³

et al. 2015

Respiration

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“…Furthermore, hierarchical clustering of the 100 most strongly regulated DEGs grouped the mice according to their experimental conditions, indicating distinct gene transcription patterns in the B cells from the four different groups (S5 Fig). Genes previously associated with EBV infection of B cells CD28 [29] and CXCL10 [30,31] were up-regulated in EBV-infected groups, whereas the PTLD-associated transcripts IL6 [25] and TNFSFR8 (CD30) [32] were upregulated specifically in the B cells from EBV-infected FK506-treated animals ( Fig 4C).…”

Section: Plos Pathogensmentioning

confidence: 78%

Immunosuppressive FK506 treatment leads to more frequent EBV-associated lymphoproliferative disease in humanized mice

et al. 2020

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Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication after organ transplantation frequently associated with the Epstein-Barr virus (EBV). Immunosuppressive treatment is thought to allow the expansion of EBV-infected B cells, which often express all eight oncogenic EBV latent proteins. Here, we assessed whether HLA-A2 transgenic humanized NSG mice treated with the immunosuppressant FK506 could be used to model EBV-PTLD. We found that FK506 treatment of EBV-infected mice led to an elevated viral burden, more frequent tumor formation and diminished EBV-induced T cell responses, indicative of reduced EBV-specific immune control. EBV latency III and lymphoproliferationassociated cellular transcripts were up-regulated in B cells from immunosuppressed animals, akin to the viral and host gene expression pattern found in EBV-PTLD. Utilizing an unbiased gene expression profiling approach, we identified genes differentially expressed in B cells of EBV-infected animals with and without FK506 treatment. Upon investigating the most promising candidates, we validated sCD30 as a marker of uncontrolled EBV proliferation in both humanized mice and in pediatric patients with EBV-PTLD. High levels of sCD30 have been previously associated with EBV-PTLD in patients. As such, we believe that humanized mice can indeed model aspects of EBV-PTLD development and may prove useful for the safety assessment of immunomodulatory therapies.

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“…One study showed five of nine cases of hairy cell leukemia were positive for cytoplasmic TIA-1, with a small, dot-like, granular expression pattern, while 94 B-cell lymphomas of other types were negative for TIA-1. Based on these findings, TIA-1 reactivity in lymphomas does not necessarily indicate a T-or NK-cell derivation [11]. Neoplastic cells in 13.7% of stage-IIIB/IV Hodgkin's lymphoma also showed expression of TIA-1 [12].…”

Section: Discussionmentioning

confidence: 93%

Diffuse Large B-Cell Lymphoma Trans-differentiating into CD30 Positive Anaplastic Large Cell-like Lymphoma

Bains¹

2017

Ann Hematol Oncol

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Post-Transplant Lymphoproliferative Disorders (PTLD) is mostly of B-cell origin. "Composite" PTLD with diffuse large B-cell lymphoma (DLBCL) and T/ anaplastic large cell lymphoma component are extremely rare. We report a case of PTLD after heart transplant with two distinct components. The patient was initially diagnosed with monomorphic PTLD/DLBCL, EBV negative involving the intestinal wall, occurring nine years after heart transplantation. Sixteen years post-transplant, the lymphoma recurred involving the intestine and showed two distinct components: DLBCL and anaplastic large cell lymphoma with strong homogeneous expression of CD45 and CD30 while lacking B-and T-cell lineage markers mimicking Anaplastic Large Cell Lymphoma (ALCL), ALK negative with a null-cell phenotype and TIA-1 expression. At this time, diffuse lymphadenopathy was also present and a jugular lymph node biopsy prior to the intestinal resection, purely demonstrated only the anaplastic large lymphoma cells with a null-cell phenotype leading to the diagnosis of ALCL, ALK negative. However, molecular studies performed on the anaplastic large cell component identified strongly positive clonal IgH gene rearrangement, identical to the prior lymphoma. Extensive sampling from the intestinal resection specimen identified a transitioning phase between two morphologically and immunohistochemically separate components. This is a unique case of PTLD which demonstrates an immunophenotypic lineage plasticity of the neoplastic cells over an extended post-transplant period.

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Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

Cited by 33 publications

References 27 publications

Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Immunosuppressive FK506 treatment leads to more frequent EBV-associated lymphoproliferative disease in humanized mice

Diffuse Large B-Cell Lymphoma Trans-differentiating into CD30 Positive Anaplastic Large Cell-like Lymphoma

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