Ruxolitinib as first‐line treatment in secondary hemophagocytic lymphohistiocytosis: A second experience

Zandvakili, Inuk; Conboy, Caitlin B.; Ayed, Ayed O.; Cathcart-Rake, Elizabeth; Tefferi, Ayalew

doi:10.1002/ajh.25063

Cited by 40 publications

(33 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Instead, its mechanism of action is based on its nonspecific ability to suppress inflammatory cytokines. Consistent with this impression, the therapeutic value of the drug has also been reported in other inflammation‐related disorders, including graft vs. host disease and secondary hemophagocytic lymphohistiocytosis …”

Section: Risk‐adapted Therapysupporting

confidence: 59%

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

2018

Self Cite

View full text Add to dashboard Cite

Observation alone is advised for MIPSS70+ version 2.0 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic stem cell transplant is the preferred treatment of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. All other treatment approaches, including the use of JAK2 inhibitors, are mostly palliative and should not be used in the absence of clear treatment indications. Conventional treatment for anemia includes androgens, prednisone, thalidomide and danazol, for symptomatic splenomegaly hydroxyurea and ruxolitinib and for constitutional symptoms ruxolitinib. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for nonhepatosplenic EMH and extremity bone pain.

show abstract

Section: Risk‐adapted Therapysupporting

confidence: 59%

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…10,11 Anecdotal experiences of successful use of ruxolitinib to control refractory primary HLH or secondary HLH are also reported in humans. [12][13][14][15][16][17][18][19] JAK1/JAK2 inhibitors are also increasingly used in inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of ruxolitinib in subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…18,19 Additionally, recent case reports reveal promising results for the use of ruxolitinib as a treatment for patients with relapsed or refractory disease. [20][21][22][23] Ruxolitinib inhibits JAK1 and JAK2, which function downstream of several cytokines, in addition to IFN-g. 24,25 As a result, it remained unknown whether the beneficial effects of ruxolitinib resulted simply from its targeting of IFN-g signaling or instead from the targeting of other cytokine signaling pathways. To gain further insights, in this study we compared the therapeutic effects of ruxolitinib with those obtained using an IFNg-blocking antibody (aIFN-g) in mouse models of primary and secondary HLH.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis

Albeituni¹,

Verbist²,

Tedrick³

et al. 2019

Blood

119

View full text Add to dashboard Cite

Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal disorder characterized by the overactivation of T cells and macrophages that excessively produce proinflammatory cytokines, including interferon-γ (IFN-γ). Previously, we reported that the JAK inhibitor ruxolitinib dampens T-cell activation and lessens inflammation in a model of HLH in which perforin-deficient (Prf1−/−) mice are infected with lymphocytic choriomeningitis virus (LCMV). Ruxolitinib inhibits signaling downstream of IFN-γ, as well as several other JAK-dependent cytokines. As a consequence, it remained unclear whether ruxolitinib was exerting its beneficial effects in HLH by inhibiting IFN-γ signaling or by targeting signaling initiated by other proinflammatory cytokines. To address this question, we compared the effects of ruxolitinib with those obtained using an IFN-γ–neutralizing antibody (αIFN-γ) in 2 murine HLH models. In both models, ruxolitinib and αIFN-γ reduced inflammation-associated anemia, indicating that ruxolitinib operates in an IFN-γ–dependent manner to reverse this HLH manifestation. In contrast, the number and activation status of T cells and neutrophils, as well as their infiltration into tissues, were significantly reduced following treatment with ruxolitinib, but they remained unchanged or were increased following treatment with αIFN-γ. Notably, despite discontinuation of ruxolitinib, LCMV-infected Prf1−/− mice exhibited enhanced survival compared with mice in which αIFN-γ was discontinued. This protective effect could be mimicked by transient treatment with αIFN-γ and a neutrophil-depleting antibody. Thus, ruxolitinib operates through IFN-γ–dependent and -independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, with the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis.

show abstract

Ruxolitinib as first‐line treatment in secondary hemophagocytic lymphohistiocytosis: A second experience

Cited by 40 publications

References 7 publications

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

Primary myelofibrosis: 2019 update on diagnosis, risk‐stratification and management

Efficacy of ruxolitinib in subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis

Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis

Contact Info

Product

Resources

About