Possible involvement of IL-6-producing tissue-resident macrophages in early-onset pericardial effusion pathogenesis after hematopoietic stem cell transplantation.

PURPOSE: Pericardial effusion (PE) is a potentially life-threatening complication following hematopoietic stem cell transplantation (HCT). A higher incidence of early-onset PE, unrelated to graft-versus-host disease, before day 100 after HCT has been reported in pediatric patients, but the pathogenic mechanism is poorly understood. Aiming to determine the pathogenesis of early-onset PE in pediatric patients, we analyzed the cytokine concentration and cell population in the pericardial fluid of four pediatric patients with PE. METHODS: Between January 2009 and December 2015, four patients requiring pericardiocentesis for clinically significant PE were identified in 60 patients. We evaluated the interleukin-6 (IL-6), interferon-γ, IL-1ß, and tumor necrosis factor-α levels in PE. Two patients were available for analysis with intracellular cytokine flow cytometry and a chimerism assay. RESULTS: All patients showed the accumulation of pericardial macrophages and high concentrations of IL-6 in PE. Notably, the accumulated pericardial macrophages were CD163+ CD15+ CD14+ cells of host origin that produced IL-6. CONCLUSION: These IL-6-producing tissue-resident macrophages may be key players in the pathogenesis of early-onset PE.

Characteristics of methotrexate-induced stroke-like neurotoxicity.

Intrathecal administration of methotrexate (IT-MTX) can lead to neurotoxicity. MTX-induced neurotoxicity occasionally manifests with a stroke-like presentation that is difficult to distinguish from genuine stroke. We retrospectively reviewed records of nine patients with leukemia or lymphoma and episodes of stroke-like presentation at our institute between 2010 and 2015 for whom magnetic resonance imaging (MRI) data were available. Coagulation test results were compared between the two diagnostic groups. Four patients were diagnosed with MTX-induced stroke-like neurotoxicity. The first neurological event occurred 10-13 days after the fourth or later IT-MTX treatment. All four patients had hemiparalysis, two exhibited disturbed consciousness and three presented with speech disorders. Fibrin/fibrinogen degradation products (FDP) and D-dimer values were within normal ranges. MRI revealed bilateral lesions with restricted diffusion in all four cases. Neurological symptoms fluctuated and resolved within 5 days, and IT-MTX was subsequently re-initiated in all four cases. One patient developed transient hemiparalysis after a subsequent IT-MTX treatment, but this did not recur thereafter. Bilateral lesions on MRI and normal coagulation are indicative of MTX-induced stroke-like neurotoxicity. Continuation of IT-MTX after these events is generally feasible, but adverse event risk should be carefully weighed against anti-tumor benefits.