Light chain amyloidosis

Light chain amyloidosis (AL) is the most common subtype of amyloidosis except wild type tranthyretine amyloidosis and is caused by the deposition of misfolded monoclonal light chains of immunoglobulins produced by a monoclonal B cell, mainly of plasma cell origin. Affected patients may present with amyloidosis alone or in association with other plasma cell or lymphoid dyscrasias (multiple myeloma, Waldenström macroglobulinemia or other B lymphoma). Diagnosis of amyloidosis is histological. Cardiac and renal involvement are the most frequent and present in nearly two thirds of patients as hypertrophic heart disease and/or nephrotic syndrome, respectively. AL amyloidosis is a clonal plasma cell disorder and is treated by chemotherapy dedicated to eradicate the underlying clone. Assessment of the severity of the disease with the Mayo Clinic score is used to guide the choice of treatment. First-line treatment combine bortezomib, cyclophosphamide or melphalan and dexamethasone for severe cases, plus or minus daratumumab, an anti-CD-38 monoclonal antibody, following the excellent results of the ANDROMEDA phase 3 study; mild cases can still benefit from melphalan and dexamethasone

Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group

Background: This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis. / Methods: A review of literature and grading of evidence as well as expert recommendations by the ESH and ISA guideline committees. / Results and Conclusions: The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis. All patients with AL amyloidosis should be considered for clinical trials where available. Daratumumab-VCD is recommended from most untreated patients (VCD or VMDex if daratumumab is unavailable). At relapse, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients’ fitness/frailty and end organ damage. Targeted agents like venetoclax need urgent prospective evaluation. Future prospective trials should include advanced stage patients to allow for evidence-based treatment decisions. Therapies targeting amyloid fibrils or those reducing the proteotoxicity of amyloidogenic light chains/oligomers are urgently needed

Using Sybil for interactive comparative genomics of microbes on the web

Motivation: Analysis of multiple genomes requires sophisticated tools that provide search, visualization, interactivity and data export. Comparative genomics datasets tend to be large and complex, making development of these tools difficult. In addition to scalability, comparative genomics tools must also provide user-friendly interfaces such that the research scientist can explore complex data with minimal technical expertise

PaCTS 1.0: a crowdsourced reporting standard for paleoclimate data

The progress of science is tied to the standardization of measurements, instruments, and data. This is especially true in the Big Data age, where analyzing large data volumes critically hinges on the data being standardized. Accordingly, the lack of community-sanctioned data standards in paleoclimatology has largely precluded the benefits of Big Data advances in the field. Building upon recent efforts to standardize the format and terminology of paleoclimate data, this article describes the Paleoclimate Community reporTing Standard (PaCTS), a crowdsourced reporting standard for such data. PaCTS captures which information should be included when reporting paleoclimate data, with the goal of maximizing the reuse value of paleoclimate datasets, particularly for synthesis work and comparison to climate model simulations. Initiated by the LinkedEarth project, the process to elicit a reporting standard involved an international workshop in 2016, various forms of digital community engagement over the next few years, and grassroots working groups. Participants in this process identified important properties across paleoclimate archives, in addition to the reporting of uncertainties and chronologies; they also identified archive-specific properties and distinguished reporting standards for new vs. legacy datasets. This work shows that at least 135 respondents overwhelmingly support a drastic increase in the amount of metadata accompanying paleoclimate datasets. Since such goals are at odds with present practices, we discuss a transparent path towards implementing or revising these recommendations in the near future, using both bottom-up and top-down approaches

[Treatment of AL amyloidosis, current data]

International audienc

Amylose AL (contribution aux études cliniques et thérapeutiques et à la modélisation expérimentale)

Les amyloses appartiennent au groupe des maladies conformationnelles des protéines. Les mécanismes de la fibrillogénèse sont de mieux en mieux compris grâce à l utilisation de peptides capables de former des fibrilles mais également des microcristaux dont la structure est proche. Dans l amylose AL les dépôts sont formés de chaînes légères (et exceptionnellement de chaînes lourdes) monoclonales d immunoglobuline. La population B à l origine de la production des chaînes légères est le plus souvent plasmocytaire dans le cadre d une immunoglobuline monoclonale isolée ou d un myélome de stade I n évoluant pratiquement jamais vers un myélome de forte masse tumorale. Le traitement repose essentiellement sur les chimiothérapies visant à supprimer la production de la chaîne légère monoclonale. Nous présentons les résultats d un essai clinique multicentrique définissant le meilleur traitement actuel de première ligne et les voies d élaboration de modèles murins d amylose AL ainsi que l exploration de 2 voies originales d immunothérapie. Nous proposons une hypothèse expliquant la non évolutivité des proliférations plasmocytaires associées aux amyloses AL.LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Extranodal natural killer/T-cell lymphoma: advances in the management.

International audiencePURPOSE OF REVIEW: Extranodal natural killer (NK)/T-cell lymphoma, nasal-type is a highly aggressive disease more frequent in Asia than in Western countries. There is no consensus treatment. The outcome depends on disease stage. Localized NK/T-cell lymphomas often respond to radiotherapy. In contrast, patients who have extensive disease or who relapse after radiotherapy have a very poor prognosis. Overall, long-term survival in these lymphomas tends to be inferior to that for other aggressive lymphomas. This review focuses on the new management modalities in light of advances in risk stratification, patient monitoring and treatment strategies. RECENT FINDINGS: Many parameters have been reported to correlate with prognosis and new staging systems have been elaborated. Detecting Epstein-Barr virus (EBV) in the bone marrow is important for staging and measuring EBV DNA in the serum improved monitoring response to therapy. Radiation modalities have been precised and new strategies combining radiation and chemotherapy have been proposed for patients with localized disease. The particular efficacy of L-asparaginase in this disease has been confirmed and L-asparaginase-based regimens have been studied in prospective trials for patients with refractory, relapsing or disseminated disease with good results. Laboratory studies may point the way toward new therapeutic approaches. SUMMARY: Early-stage disease is treated by involved-field radiotherapy with adjuvant chemotherapy. L-Asparaginase-containing regimens are the mainstay of treatment for advanced or disseminated disease. The role of targeted therapies, autologous and allogeneic haematopoietic stem cell transplantation is yet to be clearly defined

[Chronic inflammatory demyelinating polyneuropathy (CIDP) revealing an associated disease diagnostic and therapeutic pitfalls]

International audienceThe objective of this case report is to illustrate the problem's diagnosis of a CIDP revealing a associated disease. The patient had initially a sensory CIDP wich respond to prednisone. After 2 years, he worsened with motor deficit, pain and atypical skin's lesions. The diagnosis of POEMS syndrome was made only in the fourth research of monoclonal gammopathy. A specific treatment was realised but too late and a important motor deficit with axonal loss unfortunately persisted

High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome.

We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced remission of plasma cell proliferation associated with marked improvement in the patients' performance status, neurologic symptoms, and other manifestations of the syndrome. HDT with stem cell support should be investigated further as a therapeutic option in patients with POEMS syndrome and disseminated plasma cell dyscrasia