EBV in Hodgkin Lymphoma

Up to 40% of Hodgkin lymphoma (HL) cases are associated with the Epstein-Barr virus (EBV). Clonal viral genomes can be found in the HL tumor cells, the Hodgkin Reed-Sternberg cells (HRS). The latent infection results in expression of the viral oncogenes LMP1 and LMP2A which contribute to generate the particular phenotype of the HRS cells. EBV does not only undergo epigenetic changes of its genome during latency, but also induces epigenetic changes in the host genome. The presence of EBV may alter the composition and activity of the immune cells surrounding the HRS cells. EBV favours a Th1 reaction, but this attempt at a cell mediated immune response appears to be ineffective. The presence of EBV in HL is associated with several clinicopathological characteristics: It is more frequent in cases with mixed cellular histology, in males, in children and older adults, and in developing countries, while the young-adult onset HL of nodular sclerosis type in industrialized countries is typically EBV-negative. Countries in the Mediterranean area often show an intermediate epidemiological pattern. Recent studies suggest a genetic predisposition to develop EBV-associated HL. Circulating EBV-DNA may serve as a biomarker to monitor response to therapy, and eventually, EBV will become a target for therapeutic intervention also in HL

Combined Modality Treatment Including Methotrexate-Based Chemotherapy For Primary CENTRAL Nervous System Lymphoma: A Single Institution Experience

Chemotherapy including high-dose methotrexate (HD-MTX), with or without radiotherapy, is standard treatment for primary central nervous system lymphoma (PCNSL). It remains controversial whether addition of other drugs will add to therapeutic efficacy. We report here on 41 patients with PCNSL treated using a combined treatment modality, including HD-MTX (3.5 g/m2 for 2 cycles) prior to whole brain radiotherapy (WBRT). In 22 patients, the chemotherapy was intensified by adding high-dose cytosine arabinoside (HD-AraC) (2g/m2 for 4 doses for 2 cycles). Complete remission at the end of the combined treatment was obtained in 23 of 34 assessable patients (67%), and the predicted 5-year overall and disease-free survival rates were 24% and 46%, respectively, without differences between treatment groups. The addition of HD-AraC was complicated by severe infections in 17/22 (77%) patients, resulting in 3 toxic deaths. Our study indicates that addition of HD-AraC may not improve clinical outcome in PCNSL, while it increases toxicity. More targeted and less toxic therapies are warranted

Epstein-Barr Virus (EBV)-Associated Haemophagocytic Syndrome

We describe the case of a 17- year old female who developed fatal haemophagocytic syndrome (HPS) one month following acute infection caused by Epstein-Barr virus (EBV). Despite initiation of treatment and reduction of EBV load, laboratory signs of HPS as severe cytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia persisted, and the patient died of multiorgan failure. HPS is a rare, but life-threatening complication of EBV infection

Anemia in Hodgkin's lymphoma: the role of interleukin-6 and hepcidin.

Contains fulltext : 88183.pdf (publisher's version ) (Open Access)PURPOSE: Cytokines play a pivotal role in Hodgkin's lymphoma (HL). Because interleukin-6 (IL-6) induces expression of hepcidin, one of the principal regulators of iron metabolism, we studied the contribution of hepcidin in anemia in HL at diagnosis. PATIENTS AND METHODS: Plasma samples from 65 patients with HL were analyzed for hepcidin levels using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry; cytokine levels were analyzed using enzyme-linked immunosorbent assays and parameters of iron metabolism and acute-phase reaction. RESULTS: Hepcidin plasma levels were significantly higher in HL patients when compared with controls, independent of the presence of anemia (P = .001). In the subset of patients with anemia, hepcidin levels inversely correlated with hemoglobin levels (P = .01). Analyzing parameters of iron metabolism, hepcidin levels showed a positive correlation with ferritin (P 2 (P = .005). CONCLUSION: Our findings suggest that in HL, hepcidin is upregulated by IL-6. Elevated hepcidin levels result in iron restriction and signs of anemia of chronic inflammation, although hepcidin-independent mechanisms contribute to development of anemia in HL

Exogenous nitric oxide enhances Cd tolerance in the rice root system by interacting with auxin

Oryza sativa L. is a worldwide food-crop frequently growing in cadmium (Cd) polluted soils. High Cd concentrations alter plant development and, in particular, the root-system, both by affecting auxin metabolism and by triggering reactive oxygen/nitrogen species (ROS/RNS), thereby affecting rice yield. In addition, Cd2+ easily enters in the rice root cells through passive transport, reaching the grains after xylem-tophloem transfer, thus becoming a threat to food security. Nitrogen monoxide (nitric oxide – NO) is a ubiquitous gaseous molecule involved in numerous animal and plant physiological processes, and it is also a mediator of plant development and of abiotic/biotic stresses response. Various reports highlight that NO has an important role in alleviating heavy metal toxicity and reducing the oxidative damages in plant organs either by enhancing the activity of antioxidant enzymes or by directly scavenging ROS. On the other hand, heavy metal-induced accumulation of NO was reported to be responsible for heavy metal toxicity. Indeed, NO can act either as a stress-inducing agent or as a protective molecule depending on its concentration, the plant tissue or age, and the type/severity of stress. At optimal levels, NO interacts with auxins [both indole-3 butyric acid (IBA) and indole-3 acetic acid (IAA)] during root growth and development. An auxin-induced NO production during many plant root responses has been suggested trough the modulation of the activity of enzymes involved in NO biosynthesis, while studies carried out with exogenous application of NO-specific donor compounds (i.e. sodium-nitroprusside, SNP) have demonstrated the involvement of the signal molecule in auxin metabolism, transport and signalling. However, the complex mechanisms underlying the interaction between NO and auxin during the metal stress is still poorly understood and need to be better investigated, together with further elucidations about the multifaceted role of NO (i.e. as a mitigating or a stressor agent) during Cd toxicity. To this aim, the effects of Cd toxicity on rice root anatomy/morphology and on H2O2 and O2●ˉ production, and the possible recovery by NO, was evaluated after 100μM Cd exposure, combined or not with SNP at 50μM. Moreover, endogenous IAA/IBA contents, transcription-levels of OsYUCCA1 and OsASA2 IAA-biosynthetic-genes, and expression of the IAA-responsive DR5::GUS construct were analysed, and the NO-epifluorescence levels measured. Our results show that exogenous treatments with the NO-donor SNP increase intracellular root NO levels in in vitro grown rice seedlings not exposed to Cd and restore the NO-levels reduced by the heavy metal. In addition, SNP treatments mitigate both the increase in the HPLC-measured root IAA levels and the alteration of its distribution monitored by the DR5::GUS system due to the toxic metal exposure. Notably, treatments with Cd alone or combined with SNP reduced YUCCA1 expression compared to the Control, while no effects were detected on ASA2, suggesting no involvement of the two IAA biosynthetic genes in the Cd-related increase of the IAA levels detected. Finally, the enhanced cellular NO-content alleviates the Cd-induced root morphological and histological damages and the root H2O2 and O2●ˉ overproduction. Moreover, exogenous NO decreases the heavy-metal uptake. All together our data highlight the beneficial effects of the NO in alleviating Cd toxicity in rice

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor

Plerixafor is widely used as up-front treatment with G-CSF to enhance peripheral blood hematopoietic stem cell output in patients failing previous mobilizations. Less frequently, plerixafor is used to rescue an unsatisfactory mobilization following chemotherapy (CT) and G-CSF. This study investigates if pre-collection factors affect the CD34+ cell harvest in chemotherapy and G-CSF mobilizations rescued by plerixafor. Clinical and hematological data relative to patients, mobilization, and apheresis products were retrospectively examined. The outcome was completing a target cell dose ≥ 2 × 106 CD34+ cells/kg at first apheresis. The effect exerted on the outcome by patient- and disease-related factors was investigated by univariate and multivariate logistic regression analysis. The analysis included data from 42 patients affected by hematological (39 patients) and non-hematological malignancies (three patients). Twenty-nine patients (69%) attained the target cell dose at first apheresis. Twelve out of the remaining 13 patients received an additional plerixafor administration, and all accomplished the transplant dose at a second apheresis procedure. Day -1 CD34+ PB count (OR1.46, 95% CI 1.1–1.9, p = 0.008) and platelet count (OR1.0, 95% CI 1.0–1.0, p = 0.033) predicted the achievement of the target dose at first apheresis, independently of pre-mobilization CT, radiation therapy, and disease status at mobilization. At ROC curve analysis, the best cut-off value predicting the successful collection at first apheresis was 7.5/µL for Day -1 CD34+ cell count (AUC 0.830, 0.69 sensitivity, and 0.92 specificity) and 75 × 109/L for Day -1 platelet count (AUC = 0.736, 0.65 sensitivity and 0.85 specificity). In conclusion, on-demand plerixafor rescue allows a successful stem cell collection, irrespectively of disease type and status, prior CT lines, and radiation exposure. Pre-apheresis CD34+ cells and platelet count predict the need for one or two aphereses

Primary myelofibrosis: when the clone manifests with Rh phenotype splitting

Rh phenotype splitting in primary myelofibrosi

Weak D Type 4.2.2 (DAR1.2) in an African child: Serology and molecular characterization

Weak D Type 4.2.2 (DAR1.2) in an African child: Serology and molecular characterizatio