Secondary haematological dysplasia after CAR-T-cell therapy for acute lymphoblastic leukaemia in children.

The use of CAR-T is becoming more widespread in the treatment of haematological malignancies. In adults, secondary myelodysplastic syndromes (MDS) after CAR-T have been described. However, there are currently no data on the risk of MDS following CAR-T in children treated for acute lymphoblastic leukaemia (ALL).

The evolving pattern of the monoclonal protein improves the IMWG 2/20/20 classification for patients with smoldering multiple myeloma.

The 2/20/20 International Myeloma Working Group (IMWG) score is the most employed risk score in clinical practice to evaluate the risk of progression from smoldering multiple myeloma (SMM) to symptomatic multiple myeloma. However, it faces a serious limitation: The risk score is applied at diagnosis and cannot be reapplied. Since a dynamic accurate patient risk assessment for progression is necessary, we aimed to investigate whether the detection of an evolving pattern in serum M-protein (SMP) improves the identification of high-risk patients.

Membrane Protein Detection and Morphological Analysis of Red Blood Cells in Hereditary Spherocytosis by Confocal Laser Scanning Microscopy.

In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculation regions, so they are prone to undergo hemolysis and phagocytosis by splenic macrophages. Mild to severe anemia arises in HS, and other derived symptoms like splenomegaly, jaundice, and cholelithiasis.

Gene Expression Analysis of the Bone Marrow Microenvironment Reveals Distinct Immunotypes in Smoldering Multiple Myeloma Associated to Progression to Symptomatic Disease.

Background: We previously reported algorithms based on clinical parameters and plasma cell characteristics to identify patients with smoldering multiple myeloma (SMM) with higher risk of progressing who could benefit from early treatment. In this work, we analyzed differences in the immune bone marrow (BM) microenvironment in SMM to better understand the role of immune surveillance in disease progression and to identify immune biomarkers associated to higher risk of progression.

Methods: Gene expression analysis of BM cells from 28 patients with SMM, 22 patients with monoclonal gammopathy of undetermined significance (MGUS) and 22 patients with symptomatic MM was performed by using Nanostring Technology.

Beyond one-way determinism: San Frediano's miracle and climate change in Central and Northern Italy in late antiquity.

Unlabelled: Integrating palaeoclimatological proxies and historical records, which is necessary to achieve a more complete understanding of climate impacts on past societies, is a challenging task, often leading to unsatisfactory and even contradictory conclusions. This has until recently been the case for Italy, the heart of the Roman Empire, during the transition between Antiquity and the Middle Ages. In this paper, we present new high-resolution speleothem data from the Apuan Alps (Central Italy).

Immunoparesis defined by heavy/light chain pair suppression in smoldering multiple myeloma shows initial isotype specificity and involves other isotypes in advanced disease.

Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous plasma cell disorder, with a highly variable clinical course. Immunoparesis, defined by total immunoglobulin measurements, has been shown to be an independent risk factor for progression to symptomatic disease. The heavy/light chain (HLC) assay allows precise measurement of the polyclonal immunoglobulin of the same isotype, enabling the evaluation of isotype-matched immunoparesis (IMI).

Defining an Ultra-Low Risk Group in Asymptomatic IgM Monoclonal Gammopathy.

We analyzed 171 patients with asymptomatic IgM monoclonal gammopathies (64 with IgM monoclonal gammopathy of undetermined significance-MGUS and 107 with smoldering Waldenström macroglobulinemia - SWM) who had a bone marrow (BM) evaluation performed at diagnosis. Abnormal free-light chain ratio (53% vs. 31%) and mutation prevalence (66% vs.

Exploring mobility in Italian Neolithic and Copper Age communities.

As a means for investigating human mobility during late the Neolithic to the Copper Age in central and southern Italy, this study presents a novel dataset of enamel oxygen and carbon isotope values (δOca and δCca) from the carbonate fraction of biogenic apatite for one hundred and twenty-six individual teeth coming from two Neolithic and eight Copper Age communities. The measured δOca values suggest a significant role of local sources in the water inputs to the body water, whereas δCca values indicate food resources, principally based on C plants. Both δCca and δOca ranges vary substantially when samples are broken down into local populations.

Magnesium in subaqueous speleothems as a potential palaeotemperature proxy.

Few palaeoclimate archives beyond the polar regions preserve continuous and datable palaeotemperature proxy time series over multiple glacial-interglacial cycles. This hampers efforts to develop a more coherent picture of global patterns of past temperatures. Here we show that Mg concentrations in a subaqueous speleothem from an Italian cave track regional sea-surface temperatures over the last 350,000 years.

Spectroscopic Evaluation of Red Blood Cells of Thalassemia Patients with Confocal Microscopy: A Pilot Study.

Hemoglobinopathies represent the most common single-gene defects in the world and pose a major public health problem, particularly in tropical countries, where they occur with high frequency. Diagnosing hemoglobinopathies can sometimes be difficult due to the coexistence of different causes of anemia, such as thalassemia and iron deficiency, and blood transfusions, among other factors, and requires expensive and complex molecular tests. This work explores the possibility of using spectral confocal microscopy as a diagnostic tool for thalassemia in pediatric patients, a disease caused by mutations in the globin genes that result in changes of the globin chains that form hemoglobin-in pediatric patients.

Platelet Dysfunction in Noonan and 22q11.2 Deletion Syndromes in Childhood.

Introduction:  An underlying thrombocytopathy seems to be responsible for hemorrhagic symptoms in patients diagnosed with 22q11.2 deletion syndrome (22q11DS) or Noonan syndrome (NS). In 22q11DS, it is explained by a defect in the membrane glycoprotein (GP) complex Ib-V-IX.

Aborted propagation of the Ethiopian rift caused by linkage with the Kenyan rift.

Continental rift systems form by propagation of isolated rift segments that interact, and eventually evolve into continuous zones of deformation. This process impacts many aspects of rifting including rift morphology at breakup, and eventual ocean-ridge segmentation. Yet, rift segment growth and interaction remain enigmatic.

Pomalidomide-dexamethasone for treatment of soft-tissue plasmacytomas in patients with relapsed / refractory multiple myeloma.

Objective: The presence of plasmacytomas (Ps) in patients with multiple myeloma (MM) is associated with a poor outcome, both in patients treated conventionally and in patients treated with novel agents. Two types of plasmacytomas have being recognized: paraskeletal plasmacytomas (PPs) and extramedullary plasmacytomas (EMPs), being the incidence of EMPs lower but with worse prognosis. Our aim has been to analyze the efficacy of the pomalidomide-dexamethasone combination in this patient profile.

Emicizumab for routine prophylaxis to prevent bleeding episodes in patients with hemophilia A.

Hemophilia A is an X-linked bleeding disorder caused by defects in the gene encoding factor VIII (FVIII). Routine prophylaxis with exogenous FVIII requires frequent intravenous injections. One of the most challenging issues in the treatment of hemophilia A is the development of alloantibodies against infused FVIII.

Loss of the Immune Checkpoint CD85j/LILRB1 on Malignant Plasma Cells Contributes to Immune Escape in Multiple Myeloma.

Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j (), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9.

Bone marrow plasma cell infiltration in light chain amyloidosis: impact on organ involvement and outcome.

Objectives: Prognosis of immunoglobulin light-chain (AL) amyloidosis depends mainly on the presence of cardiac involvement and the disease burden. A higher bone marrow plasma cell (BMPC) burden has been recognized as an adverse prognostic factor. The aim of our study was to analyze the correlation between the BMPC infiltration, clinical features and outcomes in patients with AL amyloidosis.

Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression.

Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012.

Prognostic impact of immunoparesis at diagnosis and after treatment onset in patients with light-chain amyloidosis.

Objectives: Immunoparesis (IP) is a risk factor associated with an unfavourable outcome in several plasma cell disorders. It has been suggested that its presence in light-chain (AL) amyloidosis could be associated with worse prognosis. However, the relevance of IP after treatment has not been evaluated to date.

Absence of spontaneous response improvement beyond day +100 after autologous stem cell transplantation in multiple myeloma.

The response evaluation after autologous stem-cell transplantation (ASCT) is usually performed at day +100 in patients with multiple myeloma (MM). A recent report suggests that improvement in the response can be observed beyond day +100. The aim of the present study has been to evaluate the rate of improved response and outcome beyond day +100 after ASCT, with and without maintenance therapy.

Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results.

The efficacy of danazol was assessed in 50 patients with myelofibrosis and anemia using the recently revised criteria of the International Working Group for Myelofibrosis Research and Treatment. According to them, anemia response (clinical improvement) is defined as transfusion cessation in transfusion-dependent patients or an Hb increase >2 g/dl in patients without transfusion requirements, both maintained for at least 12 weeks. Median follow-up from danazol start was 36 months (interquartile range [IQR] 19.

Evidence for obliquity forcing of glacial Termination II.

Variations in the intensity of high-latitude Northern Hemisphere summer insolation, driven largely by precession of the equinoxes, are widely thought to control the timing of Late Pleistocene glacial terminations. However, recently it has been suggested that changes in Earth's obliquity may be a more important mechanism. We present a new speleothem-based North Atlantic marine chronology that shows that the penultimate glacial termination (Termination II) commenced 141,000 +/- 2500 years before the present, too early to be explained by Northern Hemisphere summer insolation but consistent with changes in Earth's obliquity.