Ruxolitinib for refractory/relapsed hemophagocytic lymphohistiocytosis

Wang, Jingshi; Wang, Yini; Lin, Wei; Wang, Xinkai; Jin, Zhili; Gao, Zhuo; Wang, Zhao

doi:10.3324/haematol.2019.222471

Cited by 108 publications

(94 citation statements)

References 25 publications

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“…A total of 5/14 patients presented with a respiratory rate > 25/ min. The median NEWS2-score at baseline was 8.5 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) indicating severe or critical COVID-19 in all patients stratified to Rux (Table 2).…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Median days from onset of first symptoms to hospitalization and to Rux treatment were 9 (4-19) and 15.5 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), respectively ( Table 3). C-reactive protein (CRP) was highly elevated in the majority with 22.3 (1.6-67) fold upper limit of normal (ULN) ( Table 4).…”

Section: Covid Inflammation Score (Cis) Stratified Medical Treatmentmentioning

confidence: 99%

“…Key to Rux efficacy is its broad anti-inflammatory activity against the myeloproliferative neoplasm (MPN) inherent cytokine storm with proinflammatory IL-1, IL-6, IL-8, IL-12, TNF-α, IFNγ, VEGF, TGFβ, FGF, PDGF, GM-CSF, and G-CSF cytokines/growth factors [11]. Rux is highly effective in off-label indications, where cytokine release plays a central role for pathogenesis: Graft versus host disease (GvHD) and hemophagocytic lymphohistiocytosis (HLH) [12][13][14][15]. Rux doses ranging from 5 mg bid (GvHD) up to 25 mg bid (HLH) were successfully used without signs of overt toxicity.…”

Section: Introductionmentioning

confidence: 99%

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The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

et al. 2020

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A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).

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Section: Patient Characteristicsmentioning

confidence: 99%

Section: Covid Inflammation Score (Cis) Stratified Medical Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

et al. 2020

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“…Cytopenia improvement was observed, allowing transfusion independence, discontinuation of corticosteroids, and hospital discharge of Ruxolitinib-treated patients [3]. Other studies also confirmed the therapeutic effect of Ruxolitinib in HLH patients [21,177].…”

Section: Ruxolitinib (Jakavi)mentioning

confidence: 68%

Covid-19 Therapy: What Have We Learned In 8 Months?

Adamczyk-Popławska

Kwiatek

2020

Postępy Mikrobiologii - Advancements of Microbiology

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Coronaviruses (CoVs) are a group of RNA viruses that infect mammals and birds. In humans, CoVs mainly cause mild diseases, including the common cold. However, in the 21 st century three pandemic strains of novel CoVs, highly pathogenic to humans, emerged. These three novel CoVs are zoonosis. In 2002-2003, we dealt with the Severe Acute Respiratory Syndrome coronavirus (currently, SARS-CoV) and in 2012, the Middle East Respiratory Syndrome coronavirus (MERS-CoV). The emergence of SARS-CoV-2 in December 2019 in Wuhan (Hubei province, China) marked the next introduction of a novel, highly pathogenic CoV into the human population [112]. In most cases, SARS-CoV-2 causes mild or moderate respiratory illness and the recovery does not require any special treatment. However, some infected individuals, with associated medical conditions, developed a severe disease called Coronavirus Disease 2019 (COVID-19) with such clinical manifestations as dyspnea, hypoxia, and lung lesions, being an indication for treatment in

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“…Ruxolitinib is a safe and effective salvage therapy to improve the inflammatory status for refractory HLH; whereas its remission depth may not be sufficient. A prospective multicenter large-scale clinical trial is underway to validate the efficacy of doxorubicin-etoposide-methylprednisolone-ruxolitinib (DEP-Ru) regimen on refractory/relapsed HLH (ClinicalTrails.gov Identifier: NCT03533790) [25]. In this case report, the patient had persistent fever, severe pancytopenia, and deterious physical conditions after giving aggressive traditional treatment regimen.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review

Wang

Jing

et al. 2019

Hematology

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Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder caused by uncontrolled inflammatory responses and the activation of T lymphocytes. This lifethreatening disease, characterized by fever, cytopenia and hepatosplenomegaly, is extremely rare during pregnancy with high mortality. Despite the improvement of treatment regimen in recent years, HLH is still a great challenge for clinicians. Here, we described a 26year-old woman who admitted to our hospital at her first pregnancy with pyrexia. Her condition continued to deteriorate after receiving broad-spectrum antimicrobials, presenting with fever, pancytopenia, hepatosplenomegaly, ferritin ≥ 500 μg/L, hemophagocytosis and low NK-cell activity. HLH was eventually diagnosed by clinical manifestation and laboratory examination results. Then the patient recovered well after treatment with etoposide combined with ruxolitinib therapy and underwent successful induced-labor operation. Additionally, we summarized similar cases from the literature to improve the management of HLH during pregnancy. In conclusion, this study highlights the challenges and difficulties in the diagnosis and management of patients with HLH during pregnancy. Moreover, this is the first case report of etoposide combined with ruxolitinib in the treatment of patients with refractory secondary HLH during pregnancy.

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Ruxolitinib for refractory/relapsed hemophagocytic lymphohistiocytosis

Cited by 108 publications

References 25 publications

The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

Covid-19 Therapy: What Have We Learned In 8 Months?

Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review

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