We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in five countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate 4-fold differences between cold and warmer climates regarding prevalence (20 versus 5 cases/million) and incidence (1.9 versus 0.48 cases/million/year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin < 8 g/dL. Identification of typical features of 'CAD-associated lymphoproliferative disorder' in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work included a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift towards deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.

Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6-7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn.

er spesialist i indremedisin og i infeksjonssykdommer, fagansvarlig overlege, enhetsleder for leger ved Avdeling for gastromedisin, infeksjon, geriatri og hud og universitetslektor. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. Bø legekontor Straumsjøen Raimonda Berkman er lege i spesialisering i allmennmedisin og fastlege. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. Medisinsk avdeling Vesterålen Nordlandssykehuset Stokmarknes Per Kristian Skorpen er spesialist i indremedisin og overlege. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. Hematologisk seksjon Nordlandssykehuset Bodø Randi Fykse Hallstensen er spesialist i indremedisin og i blodsykdommer og fagansvarlig overlege. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. Seksjon for klinisk immunologi og infeksjonsmedisin Oslo universitetssykehus, Rikshospitalet og Universitetet i Oslo En mann i 50-årene med tilbakevendende urtikaria, feber og leddsmerter | Tidsskrift for Den norske legeforening

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