Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

Morscio, Julie; Tousseyn, Thomas

doi:10.5500/wjt.v6.i3.505

Cited by 63 publications

(54 citation statements)

References 100 publications

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“…There were 5 lymphoma events that occurred in the tofacitinib renal transplant program ; 4 occurred in patients positive for EBV; however, these patients received an initial higher dose of tofacitinib and multiple concomitant immunosuppressive therapies in addition to tofacitinib. In addition, it is recognized that approximately 70% of post‐transplant lymphoproliferative disorders are positive for EBV .…”

Section: Discussionmentioning

confidence: 99%

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

Mariette

Chen

Biswas

et al. 2018

Arthritis Care & Research

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ObjectiveTofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program.MethodsLymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1–30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease‐modifying antirheumatic drugs. Lymphoma incidence rates (IRs; number of patients with events/100 patient‐years) and standardized incidence ratios (SIRs) were calculated. A descriptive case–matched control analysis (1:4) was performed to identify potential risk factors for lymphoma.ResultsA total of 6,194 patients received tofacitinib (19,406 patient‐years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (IR 0.10 [95% confidence interval (95% CI) 0.06–0.15]), with no increase observed with time of exposure. The age‐ and sex‐adjusted SIR of lymphoma was 2.62 (95% CI 1.58–4.09) (Surveillance, Epidemiology, and End Results [SEER] program database). The clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein‐Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sjögren's syndrome and were positive for anti–cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls.ConclusionIn the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.

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Section: Discussionmentioning

confidence: 99%

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

Mariette

Chen

Biswas

et al. 2018

Arthritis Care & Research

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“…It should be noted that not all cases of PTLD are associated with EBV, and that EBV -negative cases, albeit very rare, were also reported. 41,42 Currently, increasingly more data points to the involvement of EBV in the development of nasopharyngeal cancer, cervical cancer (along with HPV), as well as breast, prostate, and gastric cancer. 43,44 The effect of EBV on the immune system causes additional pathologies.…”

Section: Risk Factorsmentioning

confidence: 99%

Viruses in transplantology

Mucha¹,

Foroncewicz²,

Dębska‐Ślizień³

et al. 2019

Polish Archives of Internal Medicine

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PART I GENERAL OVERVIEW OF MAJOR VIRAL INFECTIONS 7 Cytomegalovirus 10 BK virus 14 Epstein-Barr virus 15 Influenza 16 Hepatitis C virus 17 HIV 21 Human papilloma virus PART II SPECIFIC ISSUES IN MANAGEMENT OF VIRAL INFECTIONS IN TRANSPLANT RECIPIENTS 23 Viruses versus myocarditis and acute coronary syndromes 24 Viruses and kidney transplant eligibility 25 Treatment of hepatitis B virus infection in transplant recipients 27 Viral infections in kidney and upper extremity transplant recipients 28 Histological diagnosis of BK virus and cytomegalovirus infections 29 Viral diarrhea 29 Ground glass opacification PART III COMMENTARY 35 The art of immunosuppression in liver transplantation: personal reflections based on a 40-year career

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“…The most common malignant PTLD subtype is post-transplant diffuse large B-cell lymphoma (PT-DLBCL), followed by Burkitt lymphoma (PT-BL) and plasmablastic lymphoma (PT-PBL). PT-BL and PT-PBL are aggressive, but poorly studied malignant PTLD subtypes [133]. Many of the reported cases of CNS lymphomas are associated with prior EBV infections [151]: this condition is estimated to occur in 3% of liver recipients [194] and in 1-2% of kidney recipients [75].…”

Section: De Novo Cns Malignanciesmentioning

confidence: 99%

Neurologic complications in kidney transplant recipients

Piotrowski¹,

Lutkowska²,

Tsibulski³

et al. 2017

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Transplantology experiences continuous growth and kidney transplantation is the most frequently transplanted solid organ. Metabolic, cardiovascular, infectious or kidney function-related aspects are widely recognised and are of key interest for transplant doctors. Neurological complications seen in these patients, although known, are less covered in the literature. According to some reports, neurologic symptoms are experienced by almost 9 per 10 transplant recipients. The intensity, severity and type of abnormalities may vary, and most frequently the complications seem to be associated with a direct or indirect effect of immunosuppressive medications, including their direct effect on cells, on blood vessels, and susceptibility to infections. Increasing age of transplant recipients and relaxation of transplantation eligibility criteria enriches the population with patients already compromised, with a higher present risk of stroke, neuropathy, malignancy etc. Research on and introduction to clinical practice of new agents like belatacept, proteasome inhibitors, or modified release formulations of tacrolimus, changes the picture and type of abnormalities within the nervous or neuromuscular system but does not eliminate them. Thus, it seems justified to remind the society of the whole array of neurologic complications they can see in their practice despite advances in the field..

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Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

Cited by 63 publications

References 100 publications

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

Viruses in transplantology

Neurologic complications in kidney transplant recipients

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