Post-transplant Lymphoproliferative Disorder: A Single-Center Experience

Ferreira, Hugo; Bustorff, Manuela; Santos, Julia M.; Ferreira, Inês; Sampaio, Susana; Salomé, I.; Bastos, Juliana; Bergantim, Rui; Príncipe, Fernando; Pestana, Manuel

doi:10.1016/j.transproceed.2015.03.017

Cited by 10 publications

(6 citation statements)

References 6 publications

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“…On the other hand, dual mTOR inhibitors have been reported to show a higher antitumoural effect than rapamycin (Zhou & Huang, ), which could represent an advantage for reducing the incidence of relapse after transplantation. Moreover, as mTOR inhibition has been shown to have a beneficial effect in the prevention and treatment of post‐transplant lymphoproliferative disorder (Cullis et al , ; Pascual, ; Ferreira et al , ), the blockade of both mTORC complexes could provide superior anti‐proliferative benefit compared to mTORC1 targeting, as suggested by the results of Furukawa et al (). Likewise, we should consider the effect of CC214 compounds on the Treg population, whose potential role in controlling GvHD has been described (Hess, ).…”

Section: Discussionmentioning

confidence: 99%

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft‐versus‐host disease control

et al. 2016

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The mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214-1 and CC214-2. In vitro studies confirmed the superior ability of CC214-1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214-1 was more efficient in inhibiting naïve T cell activation and the expression of T-cell activation markers. In addition, CC214-1 induced specific tolerance against alloantigens, while preserving anti-cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214-2 significantly improved mice survival and decreased GvHD-induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214-1 on T lymphocytes and illustrates the role of CC214-2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.

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Section: Discussionmentioning

confidence: 99%

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft‐versus‐host disease control

et al. 2016

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“…Therefore, the optimal management of patients with PTLD is yet to be determined. Moreover, the associations of PTLD with patient and graft survival, 3,[24][25][26] return to chronic dialysis, 12,20,[24][25][26][27][28] and death with graft function 5,7,9,20 vary widely between existing studies and depend on factors such as the severity of PTLD, recipient age, and posttransplant monitoring of patients. 24 In order to provide additional insights into the incidence, risk factors, clinical management, and outcomes of PTLD in kidney recipients, we undertook a longitudinal, observational cohort study from Toronto General Hospital (TGH), the largest kidney transplant center in Canada.…”

Section: Introductionmentioning

confidence: 99%

Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

et al. 2019

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Background: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients. Design: This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes. Results: Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein-Barr virus (EBV) mismatched (Dþ/RÀ) transplants and 12 from EBV-positive recipients (Rþ). Recipients with Dþ/RÀ matches were at a significantly higher risk of developing PTLD than Rþ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78). Discussion: Epstein-Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.

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“…However, the detailed medication options are still controversial. One study showed that switching from calcineurin inhibitors to sirolimus could suppress the tumor growth and induce necrosis at the tumor center[8]. However, some evidence has indicated that mechanistic target of rapamycin (mTOR) inhibitors might increase the risk of PTLD[9], which requires further confirmation; (2) Rituximab treatment should be started as early as possible for PTLD, which is mainly caused by B-cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus-positive post-transplant lymphoproliferative disordepresenting as hematochezia and enterobrosis in renal transplant recipients in China: A report of two cases

Sun

Fan

et al. 2019

WJCC

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BACKGROUNDPost-transplant lymphoproliferative disorder (PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD.CASE SUMMARYWe report two Epstein-Barr virus (EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD.CONCLUSIONPTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.

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Post-transplant Lymphoproliferative Disorder: A Single-Center Experience

Cited by 10 publications

References 6 publications

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft‐versus‐host disease control

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft‐versus‐host disease control

Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Epstein-Barr virus-positive post-transplant lymphoproliferative disordepresenting as hematochezia and enterobrosis in renal transplant recipients in China: A report of two cases

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