Effect of mirasol pathogen reduction technology system on immunomodulatory molecules of apheresis platelets.

Pathogen inactivation for platelets by riboflavin system (MIRASOL) efficiently reduces transfusion related pathogen transmission. However little is known about its impact on platelets' immunomodulatory biochemical profile. We aimed was to assess the effects of MIRASOL treatment on platelet quality parameters and immunomodulatory molecules CD62P, RANTES, and CD40L in Single Donor Platelets (SDPs) resuspended in plasma (SDP-P) or T-PAS and additive solution (SDP-A). Twenty nine SDPs (15 SDP-P and 14 SDP-A) were included in the study. Samples were collected before, after MIRASOL treatment and just before transfusion. P-selectin (CD62P), RANTES, and CD40L were tested by ELISA. Platelet products quality assays were also performed. Platelet count/unit decreased after Mirasol treatment by 13 %. The pH of all units decreased over the 5-day storage period but remained above expected limits and the swirling test was positive throughout storage. P-selectin levels were not different between the three different time points in both SDPs-P and SDPs-A while RANTES levels were found to differ statistically significantly at the three different time points in all units and in the SPD-A subgroup. CD40L levels in all SDP products increased slightly during storage but this was not statistically significant. CD62P, RANTES, and CD40L in all time points were elevated in SDPs-A compared to SDPs-P but not at a statistically significant level. In conclusion MIRASOL treatment apart from RANTES increase does not seem to substantially affect platelets associated other cytokines and immunomodulatory molecules namely P-selectin and sCD40L which are implicated in immune transfusion reactions.

A case of Alemtuzumab-induced neutropenia in multiple sclerosis in association with the expansion of large granular lymphocytes.

BACKGROUND: Alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in Multiple Sclerosis (MS) patients compared to ß-interferon. It acts against CD52, leading primarily to lymphopenia. Recent data have shown that mild neutropenia is observed in 16% of treated MS-patients whereas severe neutropenia occurred in 0.6%. CASE PRESENTATION: Herein, we present the case of a 34-year-old woman with relapsing-remitting MS, with a history of treatment with glatiramer acetate and natalizumab, who subsequently received Alemtuzumab (12 mg / 24 h × 5 days). 70-days after the last Alemtuzumab administration, the patient displayed neutropenia (500 neutrophils/µL) with virtual absence of B-cells (0.6% of total lymphocytes), low values of CD4-T-cells (6.6%) and predominance of CD8-T-cells (48%) and NK-cells (47%); while large granular lymphocytes (LGL) predominated in the blood-smear examination. Due to prolonged neutropenia (5-days) the patient was placed on low-dose corticosteroids leading to sustained remission. CONCLUSION: This is the first case of a patient with relapsing-remitting MS with neutropenia two months post-Alemtuzumab, with simultaneous presence of LGL cells in the blood and a robust therapeutic response to prednisolone. We recommend testing with a complete blood count every 15 days in the first 3 months after the 1st Alemtuzumab administration and searching for large granular lymphocytes cell expansion on microscopic examination of the peripheral blood if neutropenia develops.

Targeting histone deacetylases in endometrial cancer: a paradigm-shifting therapeutic strategy?

OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. RESULTS: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. CONCLUSIONS: The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.

Alloimmunisation during pregnancy in Greece: need for nationwide HDFN prevention programme.

AIM/OBJECTIVES: To access the incidence and specificity of maternal red blood cells alloimmunisation and its relevant clinical impact in Greece. BACKGROUND: The rate of alloimmunisation in pregnant women in Greece is unknown. MATERIALS/METHODS: We performed a 4-year study in two tertiary hospitals in Greece. Demographics, transfusion and obstetric history were analysed. Maternal alloimmunisation was detected with indirect anti-globulin test. RESULTS: We investigated 4368 pregnant women. Of which 3292 (75·37%) were Greek and 1076 (24·63%) were migrants. In 39 alloimmunised women, 41 alloantibodies were detected (0·89%). The incidence of alloimmunisation was 0·66% (22/3292) in Greeks and 1·76% (17/1076) in migrants (P = 0·01). Anti-D was the most frequent alloantibody (0·18%). Anti-D was more frequent in migrants; 5·76% compared to 0·56% in Greek RhD negative women (P = 0·002). Other antibody specificities in declining frequency rank were anti-K, anti-E, anti-Lea, anti-M, anti-c, anti-Ce, anti-Jka, anti-Jkb and anti-C. Primiparae vs para >2 and past history of blood transfusion were significantly associated with alloimmunisation during pregnancy (P = 0·0088, P < 0·0001, respectively). CONCLUSIONS: Our results depict differences in the delivery of health care between migrants and Greek women, as well as the heterogeneity in practices for the prevention of haemolytic disease of foetus and newborn in Greece and highlight the need for the implementation of nationwide guidelines.

Monoclonal gammopathies in B-cell non-Hodgkin's lymphomas.

The association of monoclonal gammopathy (MG) with B-cell non-Hodgkin's lymphomas (NHL) is a well known phenomenon. The aim of the present work was to study the incidence, type of monoclonal component and prognostic significance of MG in a population of 255 cases with B-cell NHL. Among 255 evaluable patients with B-cell NHL, 145 were males and 110 females with a median age of 58 years (range 18-85). There were 166 patients with the various subtypes of aggressive (intermediate/high grade) NHL and 89 with the various subtypes of low risk. MG was detected in 44 patients (17.2%) with a median age of 61 years (range 23-79). There were 22 cases (8.6%) with IgG type (IgG/(k) 15, IgG/(lambda) 7), 4 cases (1.6%) with (IgA/(k) 3, IgA/(lambda) 1) and 18 cases (7.0%) with IgM (IgM/(k) 12 IgM/(lambda) 6). MG was found in 15.6% of the patients with aggressive NHL, while in low risk NHL the incidence was 20.2% (N.S.). The type of MG according to histological classification was as follows: Aggressive NHL: IgG 17 cases, IgA 2 cases, IgM 7 cases: low risk NHL: IgG 5 cases, IgA 2 cases, IgM 11 cases. The distribution of MG according to stage of the disease was as follows: stage I (4.5%), stage II (18%), stage III (6.8%) and stage IV (70.4%). The median survival of patients with aggressive NHL with MG was 17 months compared to 40 months of those without (P=0.22). Similarly the median survival of patients with low risk NHL and MG was 51.5 months compared to 38.5 months of those without (P=0.90). In conclusion MG was detected in 17.2% of cases with B-cell NHL. IgG-MG was more frequent in cases with aggressive NHL, while IgM in cases with low risk NHL. MG was mostly associated with advanced stage and had not any prognostic significance on survival.