Intravenous itraconazole for treating invasive pulmonary aspergillosis in neutropenic patients with acute lymphoblastic leukemia.

Aspergillus infection is associated with a high mortality rate in immunocompromised hosts; more effective drugs for this infection are needed. Oral itraconazole has been studied in neutropenic fungus-infected patients. Using a novel formulation (intravenous) of itraconazole, we successfully treated severe necrotizing pneumonias due to Aspergillus species occurring during a postchemotherapy prolonged aplastic phase in two patients with acute lymphoblastic leukemia

Endothelial cell activation by SARS-CoV-2 spike S1 protein: A crosstalk between endothelium and innate immune cells

Background. Emerging evidences suggest that in severe COVID-19, multi-organ failure is associated with a hyperinflammatory state (the so-called “cytokine storm”) in combination with the development of a prothrombotic state. The central role of endothelial dysfunction in the pathogenesis of the disease is to date accepted, but the precise mechanisms underlying the associated coagulopathy remain unclear. Whether the alterations in vascular homeostasis directly depend upon the SARS-CoV-2 infection of endothelial cells or, rather, occur secondarily to the activation of the inflammatory response is still a matter of debate. Here, we address the effect of the SARS-CoV-2 spike S1 protein on the activation of human lung microvascular endothelial cells (HLMVEC). In particular, the existence of an endothelium-macrophage crosstalk in the response to the spike protein has been explored. Methods and Results. The effect of the spike protein is addressed in human lung microvascular endothelial cells (HLMVEC), either directly or after incubation with a conditioned medium (CM) of human monocyte-derived macrophages (MDM) previously activated by the spike S1 protein (CM-MDM). Both MDM and HLMVEC are activated in response to the S1 protein, with an increased expression of pro-inflammatory mediators. However, when HLMVEC are exposed to CM-MDM, an enhanced cell activation occurs in terms of the expression of adhesion molecules, pro-coagulant markers, and chemokines. Under this experimental condition, ICAM-1 and VCAM-1, the chemokines CXCL8/IL-8, CCL2/MCP1, and CXCL10/IP-10 as well as the protein tissue factor (TF) are markedly induced. Instead, a decrease of thrombomodulin (THBD) is observed. Conclusion. Our data suggest that pro-inflammatory mediators released by spike-activated macrophages amplify the activation of endothelial cells, likely contributing to the impairment of vascular integrity and to the development of a pro-coagulative endothelium

Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells

Desmopressin (dDAVP) is the best characterized analogue of vasopressin, the endocrine regulator of water balance endowed with potent vasoconstrictive effects. Despite the use of dDAVP in clinical practice, ranging from the treatment of nephrogenic diabetes insipidus to bleeding disorders, much remains to be understood about the impact of the drug on endothelial phenotype. The aim of this study was, thus, to evaluate the effects of desmopressin on the viability and function of human pulmonary microvascular endothelial cells (HLMVECs). The results obtained demonstrate that the vasopressor had no cytotoxic effect on the endothelium; similarly, no sign of endothelial activation was induced by dDAVP, indicated by the lack of effect on the expression of inflammatory cytokines and adhesion molecules. Conversely, the drug significantly stimulated the production of nitric oxide (NO) and the expression of the inducible isoform of nitric oxide synthase, NOS2/iNOS. Since the intracellular level of cAMP also increased, we can hypothesize that NO release is consequent to the activation of the vasopressin receptor 2 (V2R)/guanylate cyclase (Gs)/cAMP axis. Given the multifaceted role of NOS2-deriving NO for many physio-pathological conditions, the meanings of these findings in HLMVECs appears intriguing and deserves to be further addressed

High number of circulating CD34+ cells in patients with myelophthisis.

Hematopoietic Stem Cells High number of circulating CD34+ cells in patients with myelophthisis Six patients with bone marrow micrometastases from solid cancers presented with increased numbers of circulating CD34+ cells; the CD34+ cell counts were very high in some cases. By contrast, no patient with metastatic cancer without bone marrow involvement showed raised numbers of circulating hemopoietic progenitors. haematologica 2005; 90:976-977 (http:/

Low-dose interleukin-2 for treating postautologous transplant cytogenetic abnormality recurrency in a case of acute myeloid leukemia with hyperdiploidy.

Adoptive immunotherapy and/or immunostimulation may be effective in treating early phases of leukemia relapsing after allogeneic transplant. Donor lymphocyte infusion (DLI) is an established treatment for cytogenetic relapse of chronic myeloid leukemia (CML) after unmanipulated or T-cell–depleted bone marrow transplant (BMT)1; favorable results have also been reported in a few cases of initial posttransplant relapse of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).2 A graft-versus-leukemia (GVL) effect as part of a manifest or occult DLI-elicited graft-versus-host disease (GVHD) is thought to be the reason for these favorable results. For patients who had received autologous transplant, attempts to elicit an antineoplastic effect by immunostimulation have been made using in vitro interleukin-2 (IL-2)–activated autologous lymphocytes and/or IL-2 in vivo administration.34 We report on the successful use of subcutaneous (sc) low-dose IL-2 in a patient suffering from AML with recurrence of cytogenetic abnormalities after autografting

Fine-needle aspiration biopsy and flow cytometry immunophenotyping of lymphoid and myeloproliferative disorders of the spleen.

BACKGROUND: Flow cytometry (FC) is a useful adjunct to fine-needle aspiration biopsy (FNAB) in the evaluation of lymphoproliferative disorders. The application of FC to FNAB of the spleen (sFNAB) is reported. METHODS: Flow cytometry was performed on 18 sFNAB collected over 3 years. The series comprised 10 cases of non- Hodgkin lymphomas (NHL), 2 cases insufficient for diagnosis, 2 cases of reactive hyperplasia (RH), and 4 cases of myeloid metaplasia (MM). FNAB was performed under ultrasound guidance using a 22-gauge needle. One or two passes were sufficient to prepare a conventional smear that was immediately evaluated to select the cases studied and to prepare a cell suspension for FC. The following fluoresceinated antibodies were used: CD3, CD19/kappa/lambda, FMC7/CD23/CD19, Bcl-2, and CD13/HLA-DR. In six cases, cytospins were also prepared for immunocytochemistry and were tested for CD20 (L26), CD45Ro, and kappa and lambda light chain expression. RESULTS: Flow cytometry contributed to the diagnosis of all cases of NHL by assessing light chain restriction. The specific subtype was also diagnosed by CD19/CD5 and CD 19/CD10 coexpression in two cases. Flow cytometry quantified the percentage of myeloid cells in MM cases and contributed to the cytologic diagnosis showing a polyclonal light chain expression in RH cases.Immunocytochemistry was effective and concordant in four cases. Patients tolerated the sFNAB well and no complications were reported. Cytologic and FC diagnoses were confirmed by follow-up and by histologic evaluation in cases in which splenectomy was performed for therapeutic purposes. CONCLUSION: Flow cytometry applied to sFNAB corroborates the cytologic diagnosis in lymphoid and myeloproliferative disorders of the spleen and allows therapeutic decisions avoiding splenectomy

Central venous catheter insertion: a bedside procedure for haematological patients.

The present management of onco-haematologic patients may require continuous infusion of cytotoxic drugs, use of drugs or concentrated ion solutions which are toxic for the endothelial wall of small vessels, infusion of large amounts of antibiotics or antimycotics, red blood cell and platelet transfusion, and not rarely parenteral nutrition. Such a complex therapy needs a vascular access by a central vein catheter (CVC) insertion. Many types of CVC are available at present: tunnelled Hickman or Hickmanlike catheters, subcutaneous ports, tunnelled catheters with Groshong valve, external untunnelled catheters

Measurement of spleen volume by ultrasound scanning in patients with thrombocytosis: a prospective study.

Spleen size was assessed in 73 patients with thrombocytosis and in 15 healthy subjects, comparing palpation with ultra-sonography (US) measurement of longitudinal diameter and volume. Intraobserver and interobserver variability for volume on US, checked in 12 patients, was very low. Correlation between spleen volume measured by US and that measured by computed tomography was excellent. Splenomegaly was detected by palpation in 25% of patients, by US assessment of longitudinal diameter in 33%, and by US assessment of volume in 52%. After diagnostic work-up, 54 patients had a diagnosis of essential thrombocythemia (ET), 4 of idiopathic myelofibrosis (IMF), and 15 of secondary thrombocytosis (ST). Spleen volume in patients with ST was in the normal range (138 ± 47 mL) and was significantly lower than that in patients with ET or IMF (370 ± 210 mL; P < .001). Thus, US-measured volume was the most sensitive method for identifying nonpalpable splenomegaly in patients with primary myeloproliferative diseases, and it may help in distinguishing these diseases from reactive disorder

Efficacy of lamivudine to prevent hepatitis reactivation in hepatitis B virus-infected patients treated for non-Hodgkin lymphoma.

The association of hepatitis viruses with non-Hodgkin lymphomas (NHL) is not rare. Several authors have reported an exceeding prevalence of hepatitis C virus (HCV)1-3 or of hepatitis B virus (HBV)4,5 infection in patients affected by NHL. A sustained increase of alanine aminotransferase (ALT) associated with high levels of HBV viremia (HBV-DNA) 1 to 2 months after the suspension of chemotherapy has been described in patients suffering from NHL and infected by HBV.7,8 Recently, a nucleotide analogue (lamivudine) was shown to be beneficial in HBV-infected patients with signs of active replication.6 The aim of this study was to investigate the role of lamivudine to treat or to prevent hepatitis reactivation in HBV-infected subjects suffering from NHL and undergoing chemotherapy

High prevalence of hepatitis C virus infection in patients with B-cell lymphoproliferative disorders in Italy.

Starting from the observation that a number of consecutive patients with non-Hodgkin's lymphoma (NHL) resulted positive for hepatitis C virus (HCV) antibodies on routine testing, we set up a survey for HCV contact prevalence in all patients with lymphoproliferative disorders (LPD) followed in our institution. We searched for HCV antibodies by a thirdgeneration ELISA technique, followed by a confirmation test (RIBA III); serum viral RNA and HCV genotype were investigated by a RT-PCR technique. We screened a total of 315 patients suffering from B-NHL (91), multiple myeloma (56), MGUS (48), chronic lymphocytic leukemia (57), Waldentrom's macroglobulinemia (13), Hodgkin's disease (HD)(43), and T-NHL (9). While only I of 52 patients with a non-B-LPD (HD or T-NHL) had signs of HCV contact (i.e., 1.9%, which is in the range of the normal population in the South of Italy), 59 of 263 patients with a B-LPD (22.4%) had HCV antibodies or RNA, or both, with no major differences among the various types of disorders, except for WM, in which the rate was higher (61.5%). The same prevalence was found for patients tested at diagnosis or during the follow-up, and in transfused or never-transfused patients. Only a few patients were aware of having a liver disease; one-half of HCV-positive patients never had transaminase increase. A review of data from Central and Northern Italy is included, showing similar findings; a report from Japan has confirmed such an association, while limited surveys in England have not revealed any correlation. These findings may have important biological and clinical implications