Efficacy
HLH, cytopenia, malignancy-associated HLH
CYTOPENIA, REMISSION, REMISSIONS
Overall, 50% (4 out of 8) of the patients achieved better remission after receiving an escalated dose of ruxolitinib. Among them, patient 1 and 5 achieved HLH improvement at the general dose of ruxolitinib (10mg twice daily and 15mg twice daily, respectively), but complete remissions were obtained only after the dose of ruxolitinib was escalated to 20mg twice daily. Patients 2 and 3 did not respond to the general dose of ruxolitinib, but achieved complete remissions of HLH after the dose of ruxolitinib was increased to 20mg twice daily in combination with triazoles (CYP450 inhibitors to increase concentration of ruxolitinib (Regarding combination therapy, four patients received concomitant treatment with CRRT, two patients with malignancy-associated HLH were treated with BCL-2 inhibitors, and three patients received corticosteroids in addition to ruxolitinib. Three patients remained on corticosteroids upon initiation of ruxolitinib and effective treatment with ruxolitinib in one of them led to a reduction in corticosteroid use. Detailed information on treatment and efficacy can be found in Treatment details and outcome of patients.Triazoles, CYP450 inhibitors.Swimmer plot of time on treatment of 8 HLH patients. Solid lines indicate that the patient died. CsA, cyclosporin A; Dex, dexamethasone; IVIG, intravenous immunoglobulin.Regarding laboratory indicators, cytopenia was substantially resolved in all four patients who responded to escalated-dose ruxolitinib. In patient 1 and 5, the improvement in cytopenia after the general-dose of ruxolitinib was insufficient for remission. However, after escalating the dose of ruxolitinib, the counts of white blood cells and platelets recovered significantly. In patient 2 and 4, cytopenia did not improve after general-dose ruxolitinib treatment. But after escalating the dose of ruxolitinib, the counts of white blood cells and platelets increased significantly (as shown in Counts of white blood cells (WBC) and platelets (PLT) before and after ruxolitinib in peripheral blood of responded patients. Initiation of ruxolitinib treatment occurred at day 0, the time point of maximum dose of escalating-ruxolitinib was indicated by the dotted line.Levels of HLH markers: serum ferritin and soluble-CD25 (sCD25) before and after ruxolitinib in peripheral blood of responded patients. Initiation of ruxolitinib treatment occurred at day 0, the time point of maximum dose of escalating-ruxolitinib was indicated by the dotted line.Levels of Alanine transaminase (ALT) and total bilirubin (T-Bil) before and after ruxolitinib in peripheral blood of responded patients. Initiation of ruxolitinib treatment occurred at day 0, the time point of maximum dose of escalating-ruxolitinib was indicated by the dotted line.Levels of fibrinogen (Fbg) and international normalized ratio (INR) before and after ruxolitinib of responded patients. Initiation of ruxolitinib treatment occurred at day 0, the time point of maximum dose of escalating-ruxolitinib was indicated by the dotted line.