Rapid Hepatomegaly From Ruxolitinib Discontinuation Syndrome.

Ruxolitinib (RUX) is a Food and Drug Administration-approved Janus Kinase (JAK) inhibitor shown to be effective in improving hypercatabolic symptoms and splenomegaly in patients with myelofibrosis (MF). RUX therapy provides symptomatic benefits for MF patients but is often discontinued for various reasons including worsening cytopenias. Ruxolitinib Discontinuation Syndrome (RDS) involves an acute cytokine-storm rebound phenomenon that can manifest as an acute relapse of symptoms, worsening splenomegaly, respiratory distress, systemic inflammatory response syndrome, or disseminated intravascular coagulopathy. We present the case of a patient with JAK2-positive post-polycythemia vera MF, whose RUX therapy was discontinued due to an active gastrointestinal (GI) bleed and worsening cytopenias. The patient had recently started azacitidine and was on the drug combination prior to hospitalization. The patient developed what appears to be the first case of acute onset accelerated massive hepatomegaly, a previously undescribed clinical manifestation of RDS. Although rare, medical professionals should maintain a high suspicion of RDS in hospitalized patients following the discontinuation of RUX.

van Rensburg RJ ，Hale S ，Calara A ，Dabb K ，Dandamudi U ，Desai P ... -  《-》

Light and shade of ruxolitinib: positive role of early treatment with ruxolitinib and ruxolitinib withdrawal syndrome in patients with myelofibrosis.

Baek DW ，Cho HJ ，Lee JM ，Kim J ，Moon JH ，Sohn SK ... -  《-》

Overcoming treatment challenges in myelofibrosis and polycythemia vera: the role of ruxolitinib.

Bryan JC ，Verstovsek S 《-》

Tuberculosis in Patients with Primary Myelofibrosis During Ruxolitinib Therapy: Case Series and Literature Review.

The selective Janus-activated kinase inhibitor ruxolitinib (rux) is now widely used to treat myelofibrosis and polycythemia vera due to its remarkable effect of reducing splenomegaly and improving constitutional symptoms. With opportunistic infections secondary to rux constantly reported; however, an increasing number of studies have begun to investigate the mechanism and underlying immunosuppressive effect of rux. We report two cases of tuberculosis (TB) in primary myelofibrosis patients during rux therapy. The first patient received rux soon after diagnosis, and tracheobronchial TB (TBTB) and bronchoesophageal fistula were found after 4 months. After discontinuation of rux, antituberculosis therapy (ATT) was introduced. The second patient initiated rux due to progressive splenomegaly after 7.5 years of interferon therapy and was diagnosed with disseminated TB after 2 months. He received ATT as well. His rux was maintained due to the high burden of systematic symptoms and splenomegaly. Both myelofibrosis and TB were well controlled in these patients. This is the first case report that describes rux-related TBTB accompanied by a bronchoesophageal fistula. Through a review of the literature, we provide supporting evidence to the finding that intrinsic disorders of myeloproliferative neoplasms and rux-induced immunologic deregulation together lead to TB. We highlight the importance of screening for latent TB infection and timely chemoprophylaxis before rux therapy. Once TB is diagnosed during treatment, rux is recommended to be stopped and active ATT should begin quickly.

Peng Y ，Meng L ，Hu X ，Han Z ，Hong Z ... -  《-》

Severe ARDS due to Ruxolitinib discontinuation syndrome: case presentation and literature review.

Discontinuation of Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, can induce symptom-relapse and even life-threatening adverse events. Due to increasing use of RUX, this so-called RUX discontinuation syndrome (RDS) is becoming more prevalent. To create better awareness for this potentially fatal syndrome, we present a case of an adult male who developed a fatal RDS. Our case presented with acute respiratory failure and a shock-like syndrome, with the need for mechanical ventilation, venovenous-extracorporeal membrane oxygenation (ECMO) and vasopressors. Respiratory symptoms quickly improved after initiation of corticosteroids, but disease course was complicated with a spontaneous spleen rupture leading to hemorrhagic shock and eventually death. This case report is the first case of severe RDS necessitating vv-ECMO and complicated with spleen rupture. Clinicians should be aware of this potentially lethal syndrome as it can present acutely but be effectively treated with corticosteroids and/or restarting JAK-inhibitors.

Houthuys JF ，Wilmer AP ，Peetermans M ，Meersseman P ，Devos T ... -  《-》