Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis (SM) defined by >20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had 'leukemic MCL' (≥ 10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy, administered to 65% of patients, and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded due to low event rates), a diagnosis of MCL-AHN (HR 4.7, 95% CI 1.7 - 13.0, p = 0.001) and abnormal karyotype (HR 5.6, 95% CI 1.4 - 13.3, p = 0.02) were associated with inferior OS; KIT D816V positivity (HR 0.33, 95% CI 0.11 - 0.98, p = 0.04) and midostaurin treatment (HR 0.32, 95% CI 0.08 - 0.72, p = 0.008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare, autoimmune or paraneoplastic condition characterized by muscle weakness and fatigability. In cancer therapy, immune checkpoint inhibitors (ICI) sensitize the immune system for tumor antigens.We report a 62-year-old, female patient with paraneoplastic LEMS as first manifestation of Merkel cell carcinoma. Under avelumab, the LEMS exacerbated with worsening of limb weakness and a severely reduced vital capacity (< 1 l). To treat this immunological side effect, we added a regimen with intravenous immunoglobulins. Hereby, the LEMS improved significantly. As we were able to continue the cancer treatment, the Merkel cell carcinoma has been in remission so far.This is the first description of paraneoplastic LEMS, avelumab, and Merkel cell carcinoma. We conclude that immunoglobulins are an option to control an ICI-associated deterioration of paraneoplastic symptoms.

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