(99m)Tc sestamibi as a prognostic factor of response to first-line therapy and outcome in patients with malignant lymphoma.

Introduction: Resistance to chemotherapy poses a major problem in cancer patients. Although of multifactorial origin, some of the implicated mechanisms also interfere with (99m)Tc-MIBI uptake and retention in cancer cells. The aim of the current study was to investigate the prognostic value of baseline (99m)Tc-MIBI imaging in lymphoma.

"Real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group.

Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (≥PR (partial response)) rate was 77.

A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies.

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012.

Metabolism-related cytokine and hormone levels in the serum of patients with myelodysplastic syndromes.

Background: A number of cytokines secreted from the bone marrow stromal cells and circulating hormones related to bone, adipose tissue and glucose metabolism might be involved in the pathogenesis of myelodysplastic syndromes (MDS).

Methods: Serum levels of cytokines related to the metabolism of bone tissue [osteocalcin and parathyroid hormone (PTH)], adipose tissue (adiponectin, leptin and ghrelin) and glucose [insulin and insulin-like growth factor-1 (IGF-1)] were determined in 72 patients suffering from MDS, mostly of the low-risk group according to FAB classification, and 41 healthy individuals (controls).

Results: Adiponectin and osteocalcin serum levels were significantly elevated in the MDS patients.

Oxidative stress due to radiation in CD34(+) hematopoietic progenitor cells: protection by IGF-1.

Radiation exerts direct as well as indirect effects on DNA through the generation of reactive oxygen species (ROS). Irradiated hematopoietic progenitor cells (HPCs) experience DNA strand breaks, favoring genetic instability, due to ROS generation. Our aim was to study the effect of a range of radiation doses in HPCs and the possible protective mechanisms activated by insulin-like growth factor-1 (IGF-1).

Alterations of deadenylase expression in acute leukemias: evidence for poly(a)-specific ribonuclease as a potential biomarker.

Background/aims: The degradation of mRNA is a key process in the control of gene expression correlated to anomalous cell proliferation. The rate-limiting step of mRNA degradation is the removal of the poly(A) tail by deadenylases. However, studies on deadenylase expression in cancer are limited.

The role of second-generation 5-HT3 receptor antagonists in managing chemotherapy-induced nausea and vomiting in hematological malignancies.

Compared with solid tumor patients, those with hematological malignancies are at particular risk of chemotherapy-induced nausea and vomiting (CINV) because of their young age, exposure to highly-emetogenic induction, consolidation and salvage regimens, the high-dose conditioning regimens used before stem cell transplantation (SCT), and the heavy psychological burden of such treatments. In the absence of prophylaxis, around 75% of patients undergoing SCT experience delayed CINV. With first-generation 5-HT(3) receptor antagonists, only about 20% are completely protected from nausea and vomiting, and this frequent and debilitating adverse event has not been fully addressed.

Simultaneous clinical resolution of focal segmental glomerulosclerosis associated with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab.

Background: Although renal involvement in advanced haematological malignancies is common, glomerulonephritis associated with lymphoproliferative disorders is rare, and the related pathogenetic mechanisms are still poorly understood. We present a rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental glomerulosclerosis with nephrotic-range proteinuria.

Case Presentation: A 53-year-old Caucasian man, previously healthy, with no history of hypertension, alcohol use or smoking presented with rapid weight gain, massive peripheral oedema, and hypertension.

Multiple autoimmune propensity and B-non-hodgkin lymphoma: cause or effect?

We report a case of multiple autoimmunity consisting of the presence of autoimmune haemolytic anaemia (AIHA), antimitochondrial antibodies (AMAs), and antiphospholipid antibodies (APLAbs) as the presenting manifestations of an extrahepatic B-non-Hodgkin lymphoma (B-NHL) in a 63-year-old woman. The patient presented with fatigue attributed to severe AIHA. Due to increased serum IgM and γ-GT levels, an investigation for AMA was performed, which proved positive with anti-M2 specificity.

Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses.

Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment.

Successful control of acute myelofibrosis with lenalidomide.

Acute panmyelosis with myelofibrosis (APMF) is a rare, fatal hematological neoplasm that is characterized by the acute onset of cytopenias and fibrosis in the bone marrow in the absence of splenomegaly or fibrosis-related morphological changes in the RBCs. We present the case of a 59-year-old female who presented with a two-month history of anemia, leucopenia and a normal platelet count. The marrow was heavily fibrotic, and no aspirate material could be obtained; the biopsy showed extensive infiltration with small to medium size megakaryocytes, dysplastic changes in the erythroid compartment, and left shift in the myeloid cells.

Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate.

Objective: Previous studies have demonstrated the feasibility of targeting lymphoma lesions with somatostatin receptor binding agents, mainly with In-111-pentetreotide. In the present work another somatostatin analog, Tc-99m depreotide, is investigated.

Methods: One-hundred and six patients, 47 with Hodgkin's (HL) and 59 with various types of non-Hodgkin's lymphoma (NHL), were imaged with both Tc-99m depreotide and Ga-67 citrate.

Autophagy: novel action of panitumumab in colon cancer.

Background: Panitumumab, a fully-human monoclonal antibody raised against epidermal growth factor receptor (EGFR), has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of patients with EGFR-expressing metastatic colorectal carcinoma (mCRC) after failure of standard chemotherapy.

Topical application of imiquimod induces alterations in peripheral blood lymphocytes in healthy individuals.

The aim of this study was to determine whether imiquimod, a Toll-like receptor-7/8 agonist, in addition to its well-known topical action on the cutaneous immune response, might also induce alterations in the peripheral blood lymphocytes. A 62.5 mg quantity of imiquimod (5% cream) was applied topically under occlusion once daily every second day for 3 weeks to the skin of 10 healthy volunteers, age range 30-57 years.

FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia.

Background: Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 x 109/L).

Abdominal radiation initiates apoptotic mechanism in rat femur bone marrow cells in vivo that is reversed by IGF-1 administration.

Purpose: Radiation induces apoptosis as a result of damage to cellular DNA and RNA. The aim of our work was to study the effect of radiation on rat bone marrow cells (as a neighboring tissue) in the context of a model of experimental radiation enteritis in rats. The effect of systematic administration in irradiated animals of r-IGF-1 and GH was also studied.

Aberrant methylation of c-myc and c-fos protooncogenes and p53 tumor suppressor gene in myelodysplastic syndromes and acute non-lymphocytic leukemia.

Purpose: Aberrant methylation, as an epigenetic phenomenon, may precede and regulate the expression of genes involved in transformation mechanisms that lead to leukemogenesis of hemopoietic cells. The genes involved mostly encode transcription factors and cell cycle specific inhibitors. The aim of this project was to study the DNA methylation pattern of c-myc, c-fos and p53 in myelodysplastic syndromes (MDS) and in acute non-lymphocytic leukemias (ANLL).

Addition of cyclosporin-A to chemotherapy in secondary (post-MDS) AML in the elderly. A multicenter randomized trial of the Leukemia Working Group of the Hellenic Society of Hematology.

In elderly patients with secondary leukemia, poor therapeutic response and low overall survival have been attributed mainly to age and to the primary resistance of leukemic cells to chemotherapy. Modulation of resistance has been attempted in different studies, but the results have been contradictory. We conducted an open, randomized multicenter clinical trial involving patients more than 60 years old with secondary leukemia preceded by a myelodysplastic syndrome.

Preoperative detection and management of immune heparin-induced thrombocytopenia in patients undergoing heart surgery with iloprost.

Objective: The objective of this study was to evaluate our protocol for the identification and management of patients with immune heparin-induced thrombocytopenia undergoing cardiac surgery.

Methods: Among 1518 patients who underwent cardiac surgery between June 1998 and May 2001, 32 (2.1%) presented with platelet counts less than 150,000/mm3 preoperatively or a history of prolonged (>3 days) intravenous exposure to heparin or both.

Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients.

Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA). We investigated the intracytoplasmic expression of type-1 [interferon gamma (IFN-gamma), interleukin (IL)-2] and type-2 (IL-4, IL-10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN-gamma and IL-2 whereas the IL-4 and IL-10 producing T cells did not differ from that of controls, resulting in a shift of IFN-gamma/IL-4 ratio towards a type-1 response.

Determination of plasma cell secreting potential as an index of maturity of myelomatous cells and a strong prognostic factor.

According to the widely accepted myeloma staging system, the bulk of paraprotein is the main determinant of disease stage. However, myelomatous plasma cells differ considerably in their ability to synthesize and secrete monoclonal paraprotein. We determined plasma cell secreting potential (PCSP) as the amount of M-component, divided by the percentage of marrow plasmacytic infiltration, in 240 patients with myeloma, and correlated our results with chain isotype, plasma cell morphology, severity of bone disease, well-recognized prognostic factors, such as serum LDH, CRP, albumin and beta2-microglobulin, treatment response and overall survival.