Ruxolitinib as Adjunctive Therapy for Hemophagocytic LymPhohistiocytosis after Liver Transplantation: A Case Report and Literature Review

He, Kun; Xu, Shidang; Shen, Lijing; Chen, Xiaosong; Xia, Qiang; Qian, Yongbing

doi:10.3390/jcm11216308

Cited by 6 publications

(2 citation statements)

References 53 publications

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“…Since pHLH can be triggered by a variety of pathogens that induce differing patterns of cytokine production, these findings suggest that ruxolitinib will be effective when HLH is induced across a spectrum of infectious agents. In line with this possibility, ruxolitinib has demonstrated benefit in treating HLH in patients with Epstein-Barr virus (40, 41), cytomegalovirus (42), influenza (43), histoplasmosis (44,45), malaria (46), and disseminated tuberculosis infections (47).…”

Section: Discussionmentioning

confidence: 97%

Cellular and transcriptional impacts of Janus kinase and/or IFN-gamma inhibition in a mouse model of primary hemophagocytic lymphohistiocytosis

et al. 2023

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BackgroundPrimary hemophagocytic lymphohistiocytosis (pHLH) is an inherited inflammatory syndrome driven by the exuberant activation of interferon-gamma (IFNg)-producing CD8 T cells. Towards this end, ruxolitinib treatment or IFNg neutralization (aIFNg) lessens immunopathology in a model of pHLH in which perforin-deficient mice (Prf1–/–) are infected with Lymphocytic Choriomeningitis virus (LCMV). However, neither agent completely eradicates inflammation. Two studies combining ruxolitinib with aIFNg report conflicting results with one demonstrating improvement and the other worsening of disease manifestations. As these studies used differing doses of drugs and varying LCMV strains, it remained unclear whether combination therapy is safe and effective.MethodsWe previously showed that a ruxolitinib dose of 90 mg/kg lessens inflammation in Prf1–/– mice infected with LCMV-Armstrong. To determine whether this dose controls inflammation induced by a different LCMV strain, we administered ruxolitinib at 90mg/kg to Prf1–/– mice infected with LCMV-WE. To elucidate the impacts of single agent versus combination therapy, Prf1–/– animals were infected with LCMV, treated or not with ruxolitinib, aIFNg or both agents, and analyzed for disease features and the transcriptional impacts of therapy within purified CD8 T cells.ResultsRuxolitinib is well-tolerated and controls disease regardless of the viral strain used. aIFNg, administered alone or with ruxolitinib, is most effective at reversing anemia and reducing serum IFNg levels. In contrast, ruxolitinib appears better than aIFNg, and equally or more effective than combination therapy, at lessening immune cell expansion and cytokine production. Each treatment targets distinct gene expression pathways with aIFNg downregulating IFNg, IFNa, and IL-6-STAT3 pathways, and ruxolitinib downregulating IL-6-STAT3, glycolysis, and reactive oxygen species pathways. Unexpectedly, combination therapy is associated with upregulation of genes driving cell survival and proliferation.ConclusionsRuxolitinib is tolerated and curtails inflammation regardless of the inciting viral strain and whether it is given alone or in combination with aIFNg. When administered at the doses used in this study, the combination of ruxolitinb and aIFNg appears no better than treatment with either drug alone in lessening inflammation. Further studies are warranted to elucidate the optimal doses, schedules, and combinations of these agents for the treatment of patients with pHLH.

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Section: Discussionmentioning

confidence: 97%

Cellular and transcriptional impacts of Janus kinase and/or IFN-gamma inhibition in a mouse model of primary hemophagocytic lymphohistiocytosis

et al. 2023

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“…The patient had been transplanted because of autoimmune cirrhosis and developed pancolonic ulcerative colitis 3 years later. 65 Ruxolitinib has also been used as adjunctive to treat hematologic disorders such as polycythemia vera, myelofibrosis, and hemophagocytic lymphohistiocytosis after liver transplantation 66,67 ; however, to date, there is no report of using JAK inhibitors to prevent acute or chronic rejection of liver allograft (Table 2).…”

Section: Jak Inhibitors In Liver Transplantationmentioning

confidence: 99%

JAK Inhibitors in Solid Organ Transplantation

Assadiasl

Mojtahedi

Nicknam

2023

The Journal of Clinical Pharma

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Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the regulation of alloimmune responses after solid organ transplantation has not yet been elucidated. In the present review, we have summarized the results of in vitro, in vivo, experimental, and clinical trial studies about the efficacy and safety of JAK inhibitors in improving allograft survival in solid organ transplantations, including kidney, heart, lung, and liver transplants. Moreover, reports on administering JAK inhibitors to steroid‐resistant patients with graft versus host disease (GvHD) after solid organ transplantation have been reviewed. Overall findings are suggestive of a beneficial role for JAK inhibitors in organ transplantation: for example, they have been shown to improve allograft function, reduce the rate and score of acute rejection, downregulate the expression of proinflammatory cytokines and adhesion molecules, and decrease oxidative stress. However, the adverse effects of these drugs, in particular bone marrow suppression and infection, remain an obstacle.

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Multiple drugs

2023

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Ruxolitinib as Adjunctive Therapy for Hemophagocytic LymPhohistiocytosis after Liver Transplantation: A Case Report and Literature Review

Cited by 6 publications

References 53 publications

Cellular and transcriptional impacts of Janus kinase and/or IFN-gamma inhibition in a mouse model of primary hemophagocytic lymphohistiocytosis

Cellular and transcriptional impacts of Janus kinase and/or IFN-gamma inhibition in a mouse model of primary hemophagocytic lymphohistiocytosis

JAK Inhibitors in Solid Organ Transplantation

Multiple drugs

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