Overall survival of myelodysplastic syndrome patients after azacitidine discontinuation and applicability of the North American MDS Consortium scoring system in clinical practice.

Background: Azacitidine (AZA) is the standard treatment for myelodysplastic syndromes (MDS); however, many patients prematurely stop therapy and have a dismal outcome.

Methods: The authors analyzed outcomes after AZA treatment for 402 MDS patients consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche, and they evaluated the North American MDS Consortium scoring system in a clinical practice setting.

Results: At treatment discontinuation, 20.

Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: A propensity score-matched analysis.

Background: Erythropoiesis-stimulating agents effectively improve the hemoglobin levels in a fraction of anemic patients with myelodysplastic syndromes (MDS). Higher doses (HD) of recombinant human erythropoietin (rhEPO) have been proposed to overcome suboptimal response rates observed in MDS patients treated with lower "standard doses" (SD) of rhEPO. However, a direct comparison between the different doses of rhEPO is lacking.

ITACA: A new validated international erythropoietic stimulating agent-response score that further refines the predictive power of previous scoring systems.

Background: In 'real-life', the Nordic score guides Erythropoietic stimulating agent (ESA) use in lower-risk myelodysplastic syndrome (MDS) with predicted response rates of 25% or 74%. As new treatments emerge, a more discriminating score is needed.

Objectives: To validate existing ESA predictive scores and develop a new score that identifies non-responders.

Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study.

Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly.

Outcome of Lower-Risk Patients With Myelodysplastic Syndromes Without 5q Deletion After Failure of Erythropoiesis-Stimulating Agents.

Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments.

Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial.

Background: In myelodysplastic syndromes, thrombocytopenia is associated with mortality, but treatments in this setting are scarce. We tested whether eltrombopag, a thrombopoietin receptor agonist, might be effective in improving thrombocytopenia in lower-risk myelodysplastic syndromes and severe thrombocytopenia.

Methods: EQoL-MDS was a single-blind, randomised, controlled, phase 2 superiority trial of adult patients with low-risk or International Prognostic Scoring System intermediate-1-risk myelodysplastic syndromes and severe thrombocytopenia.

Early lenalidomide treatment for low and intermediate-1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence.

Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136), TI with hemoglobin (Hb) ≥10 mg/dL (n = 88), or TI with Hb <10 mg/dL (n = 96).

Age and comorbidities deeply impact on clinical outcome of patients with myelodysplastic syndromes.

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients.

Methods: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed.

Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of immunosuppressive type 2 skewed macrophages.

Hepatocyte growth factor, produced by stromal and follicular dendritic cells, and present at high concentrations in the sera of patients with chronic lymphocytic leukemia, prolongs the survival of leukemic B cells by interacting with their receptor, c-MET. It is, however, unknown whether hepatocyte growth factor influences microenvironmental cells, such as nurse-like cells, which deliver survival signals to the leukemic clone. We evaluated the expression of c-MET on nurse-like cells and monocytes from patients with chronic lymphocytic leukemia and searched for phenotypic/functional features supposed to be influenced by the hepatocyte growth factor/c-MET interaction.

Cardiovascular adverse events complicating the administration of rituximab: report of two cases.

Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It is widely used in combination with polychemotherapy regimens for the treatment of hematological disorders. There is no evidence of direct cardiotoxicity of the drug but a few cases of cardiovascular adverse events have been reported in the literature.

Lenalidomide in International Prognostic Scoring System Low and Intermediate-1 risk myelodysplastic syndromes with del(5q): an Italian phase II trial of health-related quality of life, safety and efficacy.

In lower-risk myelodysplastic syndromes (MDS) with del(5q), lenalidomide induces erythroid responses associated with better survival. In a phase II, single-arm trial, 45 patients with anemia and lower-risk del(5q) MDS received lenalidomide 10 mg/day to evaluate quality of life (QoL) changes, measured by QOL-E, safety, responses and survival. Lenalidomide was well tolerated, with 80% completing ≥ 24 weeks of treatment.

Weekly standard doses of rh-EPO are highly effective for the treatment of anemic patients with low-intermediate 1 risk myelodysplastic syndromes.

For more than 20 years erythropoietin (rHEPO) has largely been used to treat anemia in myelodysplastic syndromes (MDS). Early clinical trials showed erythroid responses in no more than 15-25% of patients. In the last decade, a better selection of MDS patients suitable for a therapeutic challenge with rHEPO, alone or in combination with G-CSF, allowed for an increased response-rate, averaging around 40%.

A randomized trial with melphalan and prednisone versus melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant.

Several trials comparing the efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in elderly patients with multiple myeloma (MM) have been reported, with inconsistent results. The primary goal of our study was to evaluate the efficacy and toxicity of MP versus MPT in newly diagnosed patients with MM who were transplant-ineligible or over age 65. A total of 135 patients were enrolled.

Polycythemia as rare secondary direct manifestation of acromegaly: management and single-centre epidemiological data.

Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy.

Impaired response to influenza vaccine associated with persistent memory B cell depletion in non-Hodgkin's lymphoma patients treated with rituximab-containing regimens.

Influenza vaccination is generally recommended for non-Hodgkin's lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for ≥6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated.

An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukemic cells through STAT3 phosphorylation: a potential role of mesenchymal cells in the disease.

Background: Chronic lymphocytic leukemia cells are characterized by an apparent longevity in vivo which is lost when they are cultured in vitro. Cellular interactions and factors provided by the microenvironment appear essential to cell survival and may protect leukemic cells from the cytotoxicity of conventional therapies. Understanding the cross-talk between leukemic cells and stroma is of interest for identifying signals supporting disease progression and for developing novel therapeutic strategies.