Conference Proceedings

Accumulation of JAK Activation-Loop Phosphorylation Promotes Type I JAK Inhibitor Withdrawal Syndrome in Myelofibrosis

Denis Tvorogov, Daniel Thomas, Nicholas PD Liau, Mara Dottore, Emma F Barry, Maya Lathi, Winnie L Kan, Tim R Hercus, Frank Stomski, Timothy P Hughes, Vinay Tergaonkar, Michael W Parker, David M Ross, Jeffrey J Babon, Ravindra Majeti, Angel F Lopez

Blood | AMER SOC HEMATOLOGY | Published : 2018


Abstract Patients with myelofibrosis who are treated with the Type I ATP competitive JAK inhibitor ruxolitinib derive symptomatic benefit from improvement in cytokine-mediated symptoms, and show cytoreductive responses in disease manifestations, such as splenomegaly or leukocytosis. However, ruxolitinib treatment does not consistently reduce JAK2 mutant allele burden nor eradicate the disease. Secondly, when ruxolitinib is withdrawn there is rapid recrudescence of cytokine-mediated symptoms within days of treatment stopping and in rare cases this has led to a life-threatening "ruxolitinib discontinuation syndrome" characterized by acute relapse of disease symptoms, splenomegal..

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