Impact of the posttransplant lymphoproliferative disorder subtype on survival

Koff, Jean L.; Li, Jingxia; Zhang, Xinyan; Switchenko, Jeffrey M.; Flowers, Christopher R.; Waller, Edmund K.

doi:10.1002/cncr.31339

Cited by 20 publications

(12 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, patient survival can be very different in different organ transplants with different locations or WHO types of PTLD. We have accounted for WHO type; T cell PTLD remained independently significant in multivariate models, consistent with other recent reports . Certain individual locations were associated with higher risk of patient death in univariate analyses in our study, but each was present in very few subjects.…”

Section: Discussionsupporting

confidence: 90%

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

et al. 2019

View full text Add to dashboard Cite

Posttransplant lymphoproliferative disorders (PTLDs), 50%‐80% of which are strongly associated with Epstein‐Barr virus (EBV), carry a high morbidity and mortality. Most clinical/epidemiological/tumor characteristics do not consistently associate with worse patient survival, so our aim was to identify if other viral genomic characteristics associated better with survival. We extracted DNA from stored paraffin‐embedded PTLD tissues at our center, identified viral sequences by metagenomic shotgun sequencing (MSS), and analyzed the data in relation to clinical outcomes. Our study population comprised 69 PTLD tissue samples collected between 1991 and 2015 from 60 subjects. Nucleotide sequences from at least one virus were detected by MSS in 86% (59/69) of the tissues (EBV in 61%, anelloviruses 52%, gammapapillomaviruses 14%, CMV 7%, and HSV in 3%). No viruses were present in higher proportion in EBV‐negative PTLD (compared to EBV‐positive PTLD). In univariable analysis, death within 5 years of PTLD diagnosis was associated with anellovirus (P = 0.037) and gammapapillomavirus (P = 0.036) detection by MSS, higher tissue qPCR levels of the predominant human anellovirus species torque teno virus (TTV; P = 0.016), T cell type PTLD, liver, brain or bone marrow location. In multivariable analyses, T cell PTLD (P = 0.006) and TTV PCR level (P = 0.012) remained significant. In EBV‐positive PTLD, EBNA‐LP, EBNA1 and EBNA3C had significantly higher levels of nonsynonymous gene variants compared to the other EBV genes. Multiple viruses are detectable in PTLD tissues by MSS. Anellovirus positivity, not EBV positivity,was associated with worse patient survival in our series. Confirmation and extension of this work in larger multicenter studies is desirable.

show abstract

Section: Discussionsupporting

confidence: 90%

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In our case series there was no difference in overall survival between CD30þ and CD30-PTLDs overall. We and others have previously shown that T-cell PTLD have a particularly poor prognosis [5,26,27]. In this case series, none of the 12 patients with T-cell PTLD survived a year.…”

Section: Discussionmentioning

confidence: 50%

CD30 expression and survival in posttransplant lymphoproliferative disorders

et al. 2020

View full text Add to dashboard Cite

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication of transplantation. For refractory and relapsed PTLD new therapies are needed, such as the antibody-drug conjugate brentuximab vedotin that targets CD30. There is limited knowledge of CD30 expression in various subtypes of PTLD and its correlation to clinicopathological features. Therefore, we studied the expression of CD30 in PTLD following solid organ transplantation and correlated CD30 expression to PTLD subtype, Epstein-Barr virus (EBV)-status, intratumoral regulatory T-cells (Tregs), clinical features, and outcome. Methods: We included 50 cases of PTLD from a nationwide study of PTLDs following solid organ transplantation in Sweden. The tumor biopsies were reevaluated, and clinical data were collected. CD30 expression on tumor cells was analyzed by immunohistochemistry with the clone Ber-H2. Thirtyone cases were stained with clone 236 A/E7 for detection of forkhead box protein 3 (FoxP3, a Treg biomarker). Results: The case series consisted of 6% polymorphic, 88% monomorphic, and 6% Hodgkin lymphoma-like PTLDs and 53% of the cases were EBVþ. Overall, 70% (35/50) of the PTLDs were CD30þ (1% CD30þ tumor cells) and 30% (15/50) were CD30-. All polymorphic PTLDs (n ¼ 3) and Hodgkin lymphomas (n ¼ 3), 88% (14/16) of non-germinal center type of diffuse large B-cell lymphoma (DLBCL), and 75% (9/12) of T-cell PTLDs were CD30þ whereas all germinal center-type of DLBCL (n ¼ 5) and Burkitt type PTLD (n ¼ 2) were CD30-. CD30þ PTLD tended to be EBVþ more frequently (p ¼ .07) and occurred earlier posttransplant (2.1 vs. 8.2 years, p ¼ .01) than CD30-PTLD. Type of transplant and localization of the tumor did not differ between the groups except that CNS engagement was more common in CD30-PTLD (p ¼ .02). CD30-status was not associated with presence of intratumoral Tregs or overall survival. Conclusion: Expression of CD30 varied with PTLD subtype. There was no association between CD30 and survival, regardless of subtype.

show abstract

“…Naturally the distribution of PTLD subtypes in the groups may affect survival. T-cell PTLDs, which have a particularly poor prognosis [2,20], were more common in the no ATG group and this may in part explain the inferior survival in this group. We also found that the non-germinal center type of DLBCL was more common in the ATG group compared with the no ATG group.…”

Section: Discussionmentioning

confidence: 95%

“…Survival in PTLD has improved in recent years due to an increased awareness of the diagnosis, the introduction of rituximab as PTLD treatment, and sequential treatment with rituximab followed by chemotherapy [13]. Older age, poor performance status, the presence of B symptoms (fever, night sweats, and weight loss), elevated serum lactate dehydrogenase (S-LDH), advanced stage, higher International Prognostic Index (IPI) score, extranodal disease, central nervous system (CNS) involvement, bone marrow involvement, monomorphic PTLD (and especially T-cell phenotype), hypoalbuminemia, elevated serum creatinine level (for kidney transplantation), type of transplant (thoracic organ), and hepatitis C infection have been reported as independent prognostic factors for inferior survival in various case series [2,5,[14][15][16][17][18][19][20]. Immunosuppressive regimens have seldom been included in these analyses of prognostic factors.…”

Section: Introductionmentioning

confidence: 99%

Prior antithymocyte globulin therapy and survival in post-transplant lymphoproliferative disorders

et al. 2021

View full text Add to dashboard Cite

Background: Treatment with antithymocyte globulin (ATG) is a well-recognized risk factor for the development of post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, but it is unknown how its use affects overall survival after PTLD. Methods: A total of 114 patients with PTLD and available data on immunosuppressive regimen were included from a nation-wide case series of solid organ transplant recipients in Sweden. Prior use of ATG was correlated to clinical features, PTLD subtype, and survival. Results: A total of 47 (41%) patients had received ATG prior to the diagnosis of PTLD. The ATG-treated patients were more likely to be recipients of hearts or lungs, and less likely of kidneys (p < 0.01). They had experienced more acute rejections (p ¼ 0.02). The PTLDs arose earlier, median 2.0 vs. 6.6 years post-transplant (p ¼ 0.002) and were more often situated in the allograft (32% vs. 7%, p < 0.001) in patients with prior ATG vs. no ATG treatment. The PTLDs in the ATG group were more often Epstein-Barr virus-positive (80% vs. 40%, p < 0.001). There were more polymorphic PTLDs (17% vs. 1.5%, p ¼ 0.004) and less T-cell PTLDs (4% vs. 19%, p ¼ 0.02) in the ATG group than in the no ATG group. Diffuse large B-cell lymphoma was equally common in patients with and without prior ATG therapy, but the non-germinal center subtype was more frequent in the ATG group (p ¼ 0.001). In an adjusted Cox proportional hazards regression model, prior ATG treatment and better performance status were associated with superior overall survival, whereas older age, T-cell subtype of PTLD, presence of B symptoms, and elevated lactate dehydrogenase were associated with inferior overall survival. Patients receiving ATG solely as rejection therapy had superior overall survival compared with those receiving ATG as induction therapy or both (p ¼ 0.03). Conclusions: ATG therapy, especially rejection therapy, prior to PTLD development is an independent prognostic factor for superior overall survival after PTLD diagnosis.

show abstract

Impact of the posttransplant lymphoproliferative disorder subtype on survival

Cited by 20 publications

References 49 publications

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

Metagenomic analysis of DNA viruses from posttransplant lymphoproliferative disorders

CD30 expression and survival in posttransplant lymphoproliferative disorders

Prior antithymocyte globulin therapy and survival in post-transplant lymphoproliferative disorders

Contact Info

Product

Resources

About