Halting targeted and collateral damage to red blood cells by the complement system.

The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes.

Monoclonal gammopathy of renal significance (MGRS) histopathologic classification, diagnostic workup, and therapeutic options.

Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). MGRS-associated kidney disorders are various and the list is still expanding. The kidney disorders can manifest as glomerular diseases, tubulopathies, and vascular involvement with varying clinical presentations. Diagnosis is often challenging because of the wide spectrum of MGRS, and it is difficult to establish a pathogenic link between the presence of the M-protein or serum free light chains and kidney diseases; further complicating accurate diagnosis is the high incidence of MGUS and/or kidney disorders, independent of MGRS, in elderly patients. However, MGRS can significantly impair kidney function. Because treatment can stop and also reverse kidney disease, early recognition is of great importance. A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease. Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes. In this review, we discuss the histopathologic classification of MGRS lesions, provide a renal and haematologic diagnostic workup, discuss treatment options for MGRS, and introduce a Benelux MGRS Working Group.

Guideline for diagnosis and treatment of Waldenström's macroglobulinaemia.

On behalf of the lymphoma and multiple myeloma working parties of the Dutch/Belgian Haemato-Oncology Foundation for Adults in The Netherlands (HOVON), we present a guideline for diagnosis and management of Waldenström's macroglobulinemia (WM). Considering the indolent behaviour and heterogeneous clinical presentation of WM, it is crucial to determine the right indications for treatment, as well as to individualise therapeutic options. There are significant differences from the approach to multiple myeloma or the treatment of other indolent non-Hodkgin lymphomas, and these results cannot always be extrapolated. There is a lack of large clinical trials due to the low incidence of WM. Based on the available data, we provide a practical diagnostic classification, as well as recommendations for first-line therapy and options for treating relapsed disease. Some typical clinical features of WM, such as autoimmune phenomena and 'IgM flare' after rituximab treatment, are highlighted. A more elaborate version of this guideline was published in the 'Nederlands Tijdschrift voor Hematologie' (Dutch Journal for Hematology) September 2012.

A survey on diagnostic methods and treatment strategies used in patients with Waldenström's macroglobulinaemia in The Netherlands.

BACKGROUND: Waldenström's macroglobulinaemia (WM) is defined as a lymphoplasmacytic lymphoma primarily located in the bone marrow, accompanied by an immunoglobulin M (IgM) monoclonal protein in the serum. The symptoms are highly variable, which can sometimes lead to a diagnostic delay. Currently, there is a wide range of therapeutic options used for the management of WM but no approved therapeutic agents are available specifically for this disease. METHODS: An online survey was prepared and sent out to haematologists and haemato-oncologists in The Netherlands, together with an invitational letter to participate. Information was gathered about the preferred methods of diagnosing and treating patients with WM in general, and about the last WM patient diagnosed in their department. RESULTS: 83 (31.8%) responses were obtained, out of which 68 (81.9%) contained responses to all three parts of the survey. The respondents most commonly used either rituximab-CVP or chlorambucil as first-line treatment, whereas rituximab in combination with purine analogues was the most frequently applied second-line treatment. The prevention of an IgM 'flare' was managed by the respondents in various ways, and rituximab maintenance treatment was not commonly used. CONCLUSION: This survey indicates that in general the diagnostic methods and treatment options for WM are well known to a representative number of Dutch haematologists. The areas of uncertainty are knowledge about asymptomatic vs symptomatic disease, risk of hyperviscosity in relation to IgM level, and the occurrence and prevention of an IgM 'flare'. These issues should be addressed in clinical research and guidelines to improve care for WM patients in The Netherlands.

[Diagnostic image (196). A newborn with fever and a swollen finger]. / Diagnose in beeld (196). Een pasgeborene met koorts en met een dik vingertje.

A 5-day-old girl was presented with monoarthritis of the proximal interphalangeal joint of the right fourth digit, without signs of septic illness or meningitis, due to group B Streptococcus agalactiae.