Capillary leak phenotype as a major cause of death in patients with POEMS syndrome

Abstract

Cause of death (COD) in POEMS (polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and skin changes) syndrome is not well described. We investigated COD in patients with POEMS syndrome treated at Mayo Clinic between 2000 and 2022. Of the 89 deaths, 49 patients had known COD and were the subject of this study. Seventeen patients died of unrelated causes, while 32 patients (65%) died from causes related to POEMS syndrome including secondary malignancies like myelodysplastic syndrome and acute leukemia (n = 5) and complications from active therapy (n = 5). Notably, 19 patients died with a stereotypic syndrome we termed capillary leak phenotype (CLP), which was characterized by refractory ascites, effusions and/or anasarca that ultimately resulted in hypotension, renal failure and cardiopulmonary arrest. Alternate causes for these symptoms, such as cardiac and hepatic etiologies, were excluded. CLP as a COD was an earlier event with a median time from diagnosis to death of 2.5 years compared to 12.0 years for all other deceased patients (p = <0.0001). By definition, treatment of terminal CLP was unsuccessful with median survival of only 4 months after CLP onset. The driver of CLP is unknown, but recognition as an entity should allow for systematic study.