ADAMTS13, von Willebrand Factor, Platelet Microparticles, Factor VIII, and Impact of Somatic Mutations in the Pathogenesis of Splanchnic Vein Thrombosis Associated with BCR-ABL-Negative Myeloproliferative Neoplasms.

Background: Myeloproliferative neoplasms (MPNs) are often associated with splanchnic vein thrombosis (SVT). Not all the factors involved in the thrombotic tendency are currently known.

Objectives: This study aims to evaluate a possible association between ADAMTS13, von Willebrand factor (VWF), platelet microvesicles (MV), and factor VIII activity (FVIII:C) with thrombotic events in MPN patients.

Platelet Microvesicles, Inflammation, and Coagulation Markers: A Pilot Study.

Background: Platelet "Microvesicles" (MVs) are studied for their role in blood coagulation and inflammation. The study aimed to establish if MVs are related to age, plasma levels of inflammation, coagulation, and fibrinolysis markers in healthy individuals.

Methods: We prospectively enrolled volunteers aged over 18 years.

Ferric Carboxymaltose and Erythropoiesis-Stimulating Agent Treatment Reduces the Rate of Blood Transfusion in Refractory Anemia.

: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the reduction of red blood cell transfusion (RBCT) rate in transfusion-dependent RA patients.

Incidence of Venous Thromboembolism in Multiple Myeloma Patients across Different Regimens: Role of Procoagulant Microparticles and Cytokine Release.

Introduction: Multiple myeloma (MM) is characterized by a high prevalence of thrombotic complications. Microvesicles (MVs) are small membrane vesicles released from activated cells, and they may potentially contribute to thrombosis. Methods: We have evaluated the plasma levels of MVs and cytokines (IL-10, IL-17, and TGF-β in MM and Watch and Wait Smoldering MM (WWSMM) from patients and related them to thrombotic complications.

Risk-tailored treatment of splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a rare lymphoproliferative disease involving B-cells and affecting elderly patients. SMZL plague peripheral blood and bone marrow, spleen. Lymph nodes are generally spared.

Personalized treatment strategies for elderly patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by ineffective hematopoiesis and peripheral cytopenia, and their possible transformation into acute myeloid leukemia (AML). They typically affect the elderly but, when making treatment decisions, considering chronological age may be insufficient because it poorly correlates with patient frailty: the challenge is to select the optimal treatment in these patients by balancing efficacy and toxicity. Areas covered: This review discusses the rationale for and methods of personalizing the treatment of elderly MDS patients.

Biosimilar epoetin alfa increases haemoglobin levels and brings cognitive and socio-relational benefits to elderly transfusion-dependent multiple myeloma patients: results from a pilot study.

Anaemia is a complication reported in up to 70% of the multiple myeloma patients (MM), with remarkable clinical, cognitive and socio-relational consequences. Anaemia relates to the course of MM, normalizing in patients during remission and reappearing in relapsing/non-responding patients. In a pilot study with 31 patients with MM and transfusion-dependent anaemia, we evaluated the effects of Binocrit (biosimilar epoetin alfa) on transfusions, haemoglobin levels, mental status (mini-mental state evaluation) and the patients' social-relational functioning and quality of life (QoL).

High rate of hepatitis B viral breakthrough in elderly non-Hodgkin lymphomas patients treated with Rituximab based chemotherapy.

Background: Rituximab-containing chemotherapies are offered to elderlies for treatment of non-Hodgkin lymphomas (NHL). From 0.7 to 27% of patients with "resolved" HBV infection develop HBV reactivation and related hepatitis during Rituximab-containing chemotherapies.

Salvage therapy with bortezomib and dexamethasone in elderly patients with relapsed/refractory multiple myeloma.

Bortezomib-dexamethasone (bort-dex) is effective for relapsed/refractory (R/R) multiple myeloma, but few data are available for elderly patients. The aim of this study was to evaluate efficacy and toxicity of bort-dex in elderly R/R MM patients. We evaluated 81 R/R MM patients treated with bort-dex.

Cooperation between pathologists and clinicians allows a better diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms.

As no specific genetic lesions have yet been identified, the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms is based on a simultaneous evaluation of the clinical, morphological and molecular features defined by the updated WHO classification, which allow most cases of full-blown disease to be classified. Nevertheless, about 10-15% of the patients have unclassifiable myeloproliferative neoplasms, most of whom are in the prodromal (early) phase of disease and identified by the presence of the JAK2 mutation, but lack the complete phenotype required by the WHO classification. The detection of these prodromal phases is extremely important in order to prevent dramatic thrombo-hemorrhagic complications and improve prognosis.

The European Consensus on grading of bone marrow fibrosis allows a better prognostication of patients with primary myelofibrosis.

We investigated the relationship between the International Prognostic Scoring System of the International Working Group for Myelofibrosis Research and Treatment and the European Consensus on grading of bone marrow fibrosis (MF) in patients with primary myelofibrosis. We compared them in 196 consecutive primary myelofibrosis patients (median follow-up 45.7 months; range 7.

Outcome of patients activating an unrelated donor search: the impact of transplant with reduced intensity conditioning in a large cohort of consecutive high-risk patients.

An unrelated donor (UD) search was submitted to the Italian Bone Marrow Donor Registry between February 2002 and December 2004, for 326 consecutive patients with hematological malignancies, eligible for a reduced intensity conditioning (RIC) UD transplant. Only two regimens were allowed: melphalan, alemtuzumab, fludarabine and total body irradiation of 200 cGy (regimen A) and thiotepa, cyclophosphamide, anti-thymocyte globulin (regimen B). The outcome of patients receiving an UD transplant (n=121) was compared with patients who did not find a donor (n=205), in a time dependent analysis, correcting for time to transplant.

Noninvasive near-infrared live imaging of human adult mesenchymal stem cells transplanted in a rodent model of Parkinson's disease.

Background: We have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson's disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats.

A randomized comparison of caspofungin versus antifungal prophylaxis according to investigator policy in acute leukaemia patients undergoing induction chemotherapy (PROFIL-C study).

Background: Invasive fungal infections (IFIs) are considered a major problem among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a multicentre study aiming to assess the comparative yield of using caspofungin versus standard policy (SP) regimens and the overall impact of IFI in routine clinical care conditions.

Methods: All AL patients receiving IFI prophylaxis according to local SP were prospectively included in the study by Northern Italy Leukaemia Group (NILG) centres.

Autologous hematopoietic stem cell transplantation in autoimmune diseases.

The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system.

Cancer stem cells in hematological disorders: current and possible new therapeutic approaches.

An increasing body of evidence has shown that hematologic malignancies, alike normal hematopoiesis, has a hierarchical structure including a stem cell compartment with self renewal capability, endowed in a neoplastic niche bearing resemblance to its normal hematopoietic counterpart. According to experimental data on NOD-SCID mice, leukemic stem cells are characterized by a CD34+/CD38- surface profile and account for 1 in 10(3) to 1 in 10(6) of the total amount of leukemic cells. The available knowledge about leukemic stem cells (LSC) has arisen the question as to whether some targeting of LSC is achieved by current treatments; the answer is dubitative at best, with the possible exception of arsenic trioxide in promyelocytic leukemia.

Antiendothelial cell antibodies induce apoptosis of bone marrow endothelial progenitors in systemic sclerosis.

Objective: Patients with systemic sclerosis (SSc) have significantly fewer and functionally impaired endothelial progenitor cells (EPC) in peripheral blood and bone marrow; further, endothelial apoptosis seems to play a primary role in the pathogenesis of vascular damage. We investigated whether the failure of bone marrow EPC is related to their apoptotic phenotype and analyzed the possible mechanisms inducing apoptosis.

Methods: The presence of apoptotic cells was investigated in bone marrow aspirates taken from patients with SSc; microvessel density (MVD) and the immunohistochemical expression of vascular endothelial growth factor (VEGF) were also measured in bone marrow biopsies.

Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis.

The Inhibitor of Apoptosis Proteins (IAPs) are important regulators of programmed cell death. XIAP is the most potent among them and is over-expressed in several hematological malignancies. Its activity is endogenously antagonized by SMAC/DIABLO, and also by small molecules mimicking Smac that can induce apoptosis in tumor cells.

Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00.

Purpose: Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates.

Patients And Methods: Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib.

A comparison between metabolic syndrome post-hematopoietic stem cell transplantation and spontaneously occurring metabolic syndrome.

Background: Hematopoietic stem cell transplantation (HSCT) is used in the treatment of several hematological and non-hematological disorders. An increasing number of long-term survivors recover from their primary disease, but they are at risk of adverse late effects, including metabolic syndrome (MS), which seems to be common in long-term survivors of HSCT.

Aim: To compare common metabolic parameters and adipohormone profiles in post-transplant and spontaneously occurring or "classic" MS patients.

The clinical and biological features of a series of immunophenotypic variant of B-CLL.

Objectives: To describe the clinical and biological features of a series of immunophenotypic variant of B-CLL (v-CLL) characterised by intermediate RMH score, in the absence of t(11;14)(q13;q32) in FISH analysis in comparison with a series of typical CLL.

Methods: We studied the clinical and biological features of 63 cases of v-CLL and 130 cases of CLL.

Results: We observed significant differences in terms of age <70 yr (P < 0.

RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant.

Purpose: The biological and clinical heterogeneity of chronic myelomonocytic leukemia features renders its classification difficult. Moreover, because of the limited knowledge of the mechanisms involved in malignant evolution, chronic myelomonocytic leukemia remains a diagnostic and therapeutic challenge and a poor prognosis disease. We aimed to verify the biological and clinical significance of the discrimination, based on the leukocyte count, between myelodysplastic chronic myelomonocytic leukemia (MD-CMML) and myeloproliferative chronic myelomonocytic leukemia (MP-CMML).

Metalloproteinase alterations in the bone marrow of ALS patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, nowadays considered as suitable candidate for autologous stem therapy with bone marrow (BM). A careful characterization of BM stem cell (SC) compartment is mandatory before its extensive application to clinic. Indeed, widespread systemic involvement has been recently advocated given that non-neuronal neighboring cells actively influence the pathological neuronal loss.

Distinct transcriptional profiles characterize bone microenvironment mesenchymal cells rather than osteoblasts in relationship with multiple myeloma bone disease.

Objective: Multiple myeloma (MM) is characterized by a high incidence of osteolytic bone lesions, which have been previously correlated with the gene expression profiles of MM cells. The aim of this study was to investigate the transcriptional patterns of cells in the bone microenvironment and their relationships with the presence of osteolysis in MM patients.

Materials And Methods: Both mesenchymal (MSC) and osteoblastic (OB) cells were isolated directly from bone biopsies of MM patients and controls to perform gene expression profiling by microarrays and real-time polymerase chain reaction on selected bone-related genes.