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.

Key Points Bendamustine-rituximab therapy results in high overall and CR rates with sustained remissions in CAD. Bendamustine plus rituximab may be considered in first line for most patients with CAD requiring therapy.

Pre-transplant samples from patients and their respective donors were screened for the most informative markers for chimerism analysis. The initial screening panel for STR-PCR analyses included seven polymorphic short tandem repeats markers among which 2-3

Several factors have been found to affect engraftment after autologous SCT (ASCT) in multiple myeloma (MM), including source of stem cells, number of infused CD34+ cells, prior use of myelotoxic agents and use of haematopoietic growth factors post ASCT. Recently, bisphosphonates were shown to delay haematological recovery after ASCT in mice when compared to untreated controls. 1 To the best of our knowledge, this has not been studied in the clinical setting. The aim of this study was to evaluate the impact of bisphosphonates on haematological recovery after ASCT in patients with MM. We analysed 207 myeloma patients transplanted in