Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib

Pálmason, Róbert; Lindén, Ola; Richter, Johan

doi:10.1186/s12878-015-0029-1

Cited by 21 publications

(15 citation statements)

References 14 publications

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“…One finding that may contribute is the increase in B lymphocytes percentage and ratio B lymphocytes/T lymphocytes in patients treated with ruxolitinib, which is not significant, probably due to the small number of patients. Other authors have also described EBV infections ruxolitinib related, in one case in CNS as our patient …”

Section: Discussionsupporting

confidence: 68%

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

et al. 2018

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Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively.Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 AE 9% and 28 AE 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 AE 11% and 58 AE 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.

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Section: Discussionsupporting

confidence: 68%

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

et al. 2018

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“…Eight papers were excluded for the following reasons: pooled analysis ( n = 1), follow‐up of phase I or II trial ( n = 1), sub‐analyses ( n = 2), data on extension phase study with a shorter follow‐up ( n = 2), redundant publications ( n = 2). Five phase III RCTs (3 phase IIIa with their most recently published extended phase (750 patients) and 2 phase IIIb RCTs (283 patients)), 6 phase IV studies (1524 patients) and 28 case report publications (31 patients, of whom 4 were included also in phase III studies and 1 in phase IV study) were included in this systematic review.…”

Section: Resultsmentioning

confidence: 99%

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

et al. 2017

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Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.

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“…This concern was first raised by the evidence that RUX‐treated patients had a higher rate of infectious complications compared to controls in both registrative COMFORT trials . This observation was rapidly expanded by several clinical cases reporting atypical and opportunistic infections during RUX therapy, including Mycobacterium tuberculosis, HBV, CMV reactivations, and fungal infections . Finally, patients with PV treated with RUX experienced a significantly higher rate of herpes zoster virus reactivations …”

Section: Discussionmentioning

confidence: 99%

“…Indeed, several abnormalities both in adaptive and innate immunity were demonstrated after RUX exposure . From a clinical point of view, opportunistic and atypical infections have been described and an increase in urogenital, respiratory tract infections together with Herpes virus reactivations, are well‐known on RUX therapy . We recently led an Italian multicenter study on 507 MF patients reporting that RUX‐exposed patients had a double risk of developing infections …”

Section: Introductionmentioning

confidence: 99%

Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib: A multicenter study on 446 patients

Polverelli

Palumbo

Binotto

et al. 2018

Hematological Oncology

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Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28%) experienced 161 infectious events (grades 3-4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.

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Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib

Cited by 21 publications

References 14 publications

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib: A multicenter study on 446 patients

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