The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study.

Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the fronto-parietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

Knowledge, attitudes and behaviors of the Italian population towards Neisseria meningitidis, Streptococcus pneumoniae and HPV diseases and vaccinations: A cross-sectional multicentre study.

OBJECTIVES: This study addressed knowledge of Streptococcus pneumoniae, Neisseria meningitidis and human papillomavirus (HPV), and attitudes and behaviours towards vaccines against them. STUDY DESIGN: This is a cross-sectional, multicentre study. METHODS: Data were collected through a questionnaire administered to 530 adults who accessed four Departments of Prevention of the Italian National Health Service in 2013. RESULTS: Less than 50% of people gave the right answer to all the questions concerning the three diseases, but 96.2%, 94% and 92.7% agreed with the importance of vaccination against N. meningitidis, S. pneumoniae and HPV, respectively, and 58.4% expressed own willingness to have their children vaccinated with N. meningitidis B vaccine. The attitude towards vaccination was more positive in women for N. meningitidis and in people having children for HPV. Furthermore, individuals giving correct answers to all knowledge items were more in favour of both HPV and S. pneumoniae vaccination. A total of 68.8%, 82.6% and 84.5% of respondents vaccinated their own children against N. meningitidis C, S. pneumoniae and HPV, respectively. About 50% of the respondents reported paediatricians' or other health professionals' recommendations as the main reason for vaccination. CONCLUSIONS: Vaccinations may be promoted through actions aimed at increasing citizens' knowledge. Health professionals should be educated to actively provide information on vaccinations in a clear, comprehensive and effective way.

Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey.

A prospective cohort study was conducted in nine hematology wards at tertiary care centres or at university hospitals located throughout Italy from January 2009 to December 2012. All of the cases of bacterial bloodstream infection (BBSI) occurring in adult patients with hematologic malignancies were included. A total of 668 bacterial isolates were recovered in 575 BBSI episodes. Overall, the susceptibility rates of Gram-negative bacteria were 59.1% to ceftazidime, 20.1% to ciprofloxacin, 79.1% to meropenem, 85.2% to amikacin, 69.2% to gentamicin and 69.8% to piperacillin/tazobactam. Resistance to third-generation cephalosporins was found in 98/265 (36.9%) of Enterobacteriaceae isolates. Among Klebsiella pneumoniae strains, 15/43 (34.9%) were resistant to carbapenems. Of 66 Pseudomonas aeruginosa isolates, 46 (69.7%) were multidrug resistant. Overall, the susceptibility rates of Gram-positive bacteria were 97.4% to vancomycin and 94.2% to teicoplanin. Among the monomicrobial cases of BBSI, the 21-day mortality rate was significantly higher for those caused by Gram-negative bacteria compared to those caused by Gram-positive bacteria (47/278, 16.9% vs. 12/212, 5.6%; p < 0.001). Among Gram-negative bacteria, the mortality rate was significantly higher for BBSI caused by K. pneumoniae, P. aeruginosa, and Acinetobacter baumannii. Our results confirm the recently reported shift of prevalence from Gram-positive to Gram-negative bacteria as causative agents of BBSIs among patients with hematologic malignancies and highlight a worrisome increasing frequency in antimicrobial resistance among Gram-negative bacteria.

Effect of mass media on influenza vaccine coverage in the season 2014/2015: a regional survey in Lazio, Italy.

INTRODUCTION: Adherence to vaccination program for Influenza virus is an important issue of Public Health in presence of many no-vaccine tendencies. The media event about some deaths, occurring after MF59 adjuvanted vaccine administration, has characterized the season 2014/15 vaccination program in Italy. Aim of the study is vaccination adherence assessment of the current season with regards to local health units (LHU) coordinators's perceptions in Lazio Region (IT). METHODS: LHU coordinators's perceptions were collected from a questionnaire that was send via email to the all 12 LHU coordinators. The questionnaire was built with 4 questions concerning the impression about the vaccination adherence of elderly people in the current season. Data from questionnaire was compared with the official coverage rate obtained by the Regional Authority. Severe adverse events were collected by 1 LHU. RESULTS: All the 12 LHU coordinators answered to our questionnaire: 7/12 (50%) predicted a coverage rate of at least 50%; 3/12 (25%) referred a coverage rate around 40-45%; 2/12 (17%) predicted a reduction of 5-10% less than the previous season. Indeed, a mean 49.1% vaccination coverage in the elderly has been reported by the Regional Authority highlighting a reduction of 10% less than the 2013/14 season coverage. No severe adverse events were observed. DISCUSSION: In our survey an important effect of media event on anti-flu vaccination program adherence has been evidenced, with a failure in communication and joint management of Public Health Institutions in Italy about efficacy and safety information of flu vaccine.

Evaluation of risk of symptomatic cytomegalovirus reactivation in myeloma patients treated with tandem autologous stem cell transplantation and novel agents: a single-institution study.

The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.

Is the adjuvanted influenza vaccine more effective than the trivalent inactivated vaccine in the elderly population? Results of a case-control study.

INTRODUCTION: Influenza illness is an important public health problem and annual vaccination is globally recommended for high risk populations. OBJECTIVE: The aim was to evaluate and compare the effectiveness of influenza vaccines in reducing hospitalizations for influenza or pneumonia during two influenza seasons in the elderly. METHODS: A case-control study was performed, using administrative database of the Local Health Unit Roma-A (LHU RM-A). The included subjects were at least 65 years old and residing in one of the four districts of the LHU. The cases were hospitalized for influenza or pneumonia during influenza season in the years 2010-2011 and 2011-2012. The controls were hospitalized in the same period, but not for influenza or pneumonia. The subjects were immunized with the trivalent inactivated influenza vaccine (TIV) in the first influenza season (2010-2011) and with the adjuvanted influenza vaccine MF59 (ATIV) in the second season (2011-2012). RESULTS: A total of 269 cases and 1247 controls were included for the 2010-2011 influenza season, and 365 cases and 1227 controls were selected for the 2011-2012 season. Up to 63.6% cases and 53.5% controls in the 2010-2011 season and 78.6% of cases and 64.1% of controls in the 2011-2012 season have not been vaccinated. Female gender and high educational level were protective factors for hospitalization. Subjects over 75 years were at high risk of hospitalization compared to 65-74 years olds. Influenza vaccination reduced significantly hospitalization in both seasons. In subjects with 65-74 years TIV was more effective than ATIV; vice versa for those over 75 years old. DISCUSSION AND CONCLUSION: TIV and ATIV reduce hospitalization for influenza or pneumonia with a variable degree of protection in different age groups. In particular, ATIV is more effective in individuals over 75 years old.

Action against vaccine-preventable infectious diseases and tuberculosis in Nomad Camps: the experience of a Local Health Unit in Rome.

In Italy the highest incidence of Tuberculosis (TB) cases is in young adult migrants. In 2011, the sanitarystaff of the Local Health Unit (ASL) Roma A promoted a vaccination campaign conducting several public health interventions in Nomad Camps. After notification of a case of TB in the Camp of Via Salaria, out of 357 Mantoux skin tests performed, 93 were positive (26%); subsequently, 5 subjects with radiographic positivity were hospitalized. The vaccination campaign was carried out to prevent the spread of infectious diseases in immigrant communities at high risk of contagion and to avoid the consequent transmission in the host country. As a result, vaccinations coverage among the residents of the Camps increased: 367 vaccinated subjects (30% more than previous year) and 612 administered vaccinations.

[Vaccination against measles, mumps and rubella in a Roma people camp in Rome, Italy]. / Vaccinazione contro Morbillo, Parotite e Rosolia in un Centro di Prima Accoglienza a Roma.

The immunization strategy aimed to the elimination of Measles and the prevention of Congenital Rubella failed to reach the planned objectives in Europe; in Italy the renewed National Elimination Plan (PNEMoRc 2010-2015) has been recently approved. The evaluation of a preventive intervention to avoid the spread of measles in a Roma people camp confirm the importance of specific vaccination in high risk populations, like nomads, in which low coverage rates are responsible for the maintenance of the disease.

NK/T-cell lymphomas 'nasal type': an Italian multicentric retrospective survey.

OBJECTIVE: To evaluate the clinical characteristics and outcome of NK/T-cell lymphoma 'nasal type' developed in Italian patients. PATIENTS: Between 1997 and 2004, 26 new cases of NK/T-cell lymphoma 'nasal type' were diagnosed in 10 Italian Hematology institutions. RESULTS: All patients were Caucasian, male/female ratio was 19/7, with a median age of 50 years (range 20-80). In 23 cases presentation at the onset was in the nasal cavity or adjacent structures, in two cases the lymphoma onset with skin lesions was followed successively by rhynopharyngeal dissemination, while the remaining case had bone marrow and lymph node involvement followed by oro-pharyngeal involvement. Regarding the stage of disease: 12 patients were in stage I; six in stage II; eight in stage IV. Diagnosis was based on the finding of a NK/T-cell phenotype at the histological and immunophenotypic examination of oropharyngeal or cutaneous lesions. All patients but one were treated with chemotherapy, alone in nine cases or associated to radiotherapy in 14 cases; two patients had chemotherapy, radiotherapy and surgery, while one patient underwent only surgery. Chemotherapy was anthracycline-based in 17 out of 25 cases. In those patients in whom radiotherapy was performed, radiation dosages ranged between 36 Gy and 47.5 Gy, with a median dosage of 40 Gy. Nine patients (34%) were responsive to the treatments: six patients obtained a complete remission and other three a partial remission. The remaining 17 patients resulted refractory or presented a limited response to therapy. The median disease-free survival was 14 months and the median overall survival time was 9 months. CONCLUSION: The results of this retrospective survey confirmed that NK/T-cell lymphoma 'nasal type' is a very rare lymphoma in the Italian population, and it is characterized by a very bad prognosis. Due to the rarity of this disease, a standardized therapeutic approach is lacking. More data are needed to know the epidemiology of this kind of lymphoma in Europe.

High-dose hydroxyurea in the treatment of poor-risk myeloid leukemias.

The aim of the study was to evaluate the antileukemic effectiveness and toxicity of high-dose hydroxyurea (HHY) and to assess its acute toxicity. Between August 1997 and October 1998, 12 consecutive adult patients (>18 years) with high-risk acute myeloid leukemia (AML) (four patients in first early relapse, seven patients with secondary AML, and one patient with de novo AML concomitant to a lymphoproliferative disorder) were enrolled to receive a single course of HY (100 mg/kg per day) until bone marrow aplasia or for a maximum of 30 days. Of the 12 patients, 5 (41.6%) achieved complete remission (CR), 1 achieved partial remission (PR), 4 were resistant to treatment, and 2 died during induction from infection. No patient with relapsed AML achieved CR, while it was achieved by five of eight patients with secondary AML at diagnosis; five of six MDR1+ patients achieved CR. As concerns follow-up of the CR patients, one did not receive any further treatment and died in CR from pulmonary aspergillosis, and one with a concomitant chronic lymphocytic leukemia (CLL) received two courses of FLAG (fludarabine, cytarabine, granulocyte colony-stimulating factor) regimen with disappearance of the clonal Ig rearrangement, but relapsed after 11 months and died from pneumonia. The remaining three patients were consolidated with two courses of high-dose cytosine arabinoside (AraC), followed by peripheral blood stem cell transplantation (PBSCT) in one patient. One of them relapsed after 3 months, while the other two are still in continuous complete remission (CCR) after 16 and 28 months, respectively. This study has demonstrated the safety and efficacy of HHY in inducing CR in AML patients with unfavorable prognosis. Despite the small number of patients, these encouraging results warrant further studies.

Infectious complications in patients with acute promyelocytic leukaemia treated with the AIDA regimen.

Infections represent a frequent complication of chemotherapy used for acute myeloid leukaemia (AML) and are associated with important toxicity frequently leading to treatment discontinuation. Acute promyelocytic leukaemia (APL) is a unique AML subset requiring tailored therapy including all-trans retinoic acid and anthracycline-based chemotherapy. We analysed in this study the incidence and type of infections complicating the clinical course of 89 consecutive APL patients receiving the AIDA protocol at a single institution. A total of 179 febrile episodes were registered during induction and consolidation, 52% of which were of unknown origin. Infections were clinically and microbiologically documented in 10.6 and 37.4% of cases, respectively. Coagulase-negative staphylococci represented the major cause of septicaemia (28%) and were more frequently isolated during induction, whereas viridans group streptococci, the second pathogen most frequently isolated from blood (27%), represented the principal pathogen detected during consolidation and were significantly associated with mucositis. Gram-negative bacteria accounted for 33.3% of all blood isolates. Fungal infections were only occasionally observed. Bloodstream infections in APL patients were compared with those documented in 271 consecutive patients affected by other subtypes of AML. The incidence of total septicaemia episodes, of staphylococcal bacteraemias and of fungaemias was significantly higher in patients with other AMLs. Empirical antibiotic therapy with ceftriaxone plus amikacin was effective in 73% of APL cases, most of the remaining cases being successfully managed by the addition of teicoplanin. One single death apparently related to infectious complication was recorded. Overall, infections led to antileukaemic treatment withdrawal in six patients, five of whom currently remain in haematologic remission for 13-106 months. These results indicate that a particular pattern of infections is observed in APL patients receiving ATRA plus anthracycline-based chemotherapy and that these appear to be effectively counteracted by standard management.

Melphalan treatment in patients with myelofibrosis with myeloid metaplasia.

Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7 months: 26 (26.3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40.4%) showed an improvement >50% (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28.4 and 26 months respectively: median survival of CR + PR patients was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the non-responders (log-rank test, P =0.002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR = 2.4) and not achieving any type of response, either partial or complete (HR = 3.9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment.

Spontaneous remission in adult patients with de novo myelodysplastic syndrome: a possible event.

BACKGROUND AND OBJECTIVES: Spontaneous remission (SR) in de novo myelodysplastic syndromes (MDS) is a rare event, which has been so far described only in children with monosomy 7. The phenomenon is extremely heterogeneous, perhaps depending on different pathogeneses of the disease. DESIGN AND METHODS: We retrospectively evaluated the outcome of 564 consecutive adult patients with primary MDS diagnosed at our Institution in a 12-year period. SR was defined as an unexpected improvement lasting more than 1 year without concomitant treatments other than vitamins or low-dose steroids (in patients with platelets < 50 x 10(9)/L). RESULTS: Nine cases of SR were observed in 3 males and 6 females (median age 38.7 years). At diagnosis, all patients had Hb levels < 10 g/dL and 8/9 required packed red cell transfusions. The median time from diagnosis to SR was 18 months (range 4-46) and all patients had normalization of peripheral blood parameters: in 2 out of 3 patients with karyotypic abnormalities at onset, a cytogenetic remission was documented. The median duration of SR was 56 months; 5 patients are still in SR and 4 patients have relapsed (1 as MDS and 3 as acute myeloid leukemia). INTERPRETATION AND CONCLUSIONS: SR is a rare (less than 2% in our experience) but possible event also in adult MDS patients. It should be kept in mind in the evaluation of experimental treatments for MDS in which very low rates of complete responses are expected.

Molecular remission following high-dose hydroxyurea and fludarabine plus cytarabine in a patient with simultaneous acute myeloid leukemia and low-grade lymphoma.

The occurrence of acute myeloid leukemia (AML) as a secondary tumor has been frequently reported in patients who received various chemotherapy regimens for hematologic malignancies wile the concomitant development of chronic lymphoproliferative diseases (CLD) and AML in previously untreated patients is extremely rare. We report a case with an apparently spontaneous occurrence of AML and non Hodgkin low-grade lymphoma diagnosed by immunological, cytogenetical and molecular analyses. In particular genetic studies allowed to identify the coexistence of a clonal lymphoid population and a myeloid blast component characterized by inv(16) marker and CBFbeta-MYH11 gene fusion. Complete remission of AML and the CLD was obtained following high doses of hydroxyurea and two consolidation cycles of fludarabine plus intermediate dose cytarabine.

Feasibility of peripheral blood stem cell rescue as intensification in elderly patients with acute myelocytic leukaemia: a pilot study from the Gimema Group. Gruppo Italiano Malattie Ematologiche Maligne Dell'Adulto.

Elderly patients with untreated acute myeloid leukaemia (AML, n = 47) tested the feasibility of out-patient consolidation therapy and post-consolidation treatment (for patients aged < 71 years) with autologous peripheral blood stem cell transplantation (APBSCT). Overall, 13 patients out of 24 (51%) who achieved complete remission (CR) were eligible for further treatment after consolidation. Five patients were primed with granulocyte colony stimulating factor (G-CSF); a suitable number of CD34+ cells were harvested in three patients and were actually autotransplanted. The toxicity of APBSCT was negligible. Psychosocial problems impaired treatment of some patients on an out-patient basis. Resistant disease, toxicity and logistic problems reduced the number of patients to whom this procedure could actually be applied.

Molecular and cytogenetic remission in a case of subtype M4E acute myelogenous leukemia with minimal monochemotherapy: high sensitivity or spontaneous remission?

Complete remission was observed in an adult patient with acute myelogenous leukemia after minimal monochemotherapy. Remission occurred after a severe febrile pneumonia and was accompanied by cytogenetic and molecular remission. The hypothesis of spontaneous remission was raised, even if a high sensitivity to low-dose cytostatics cannot be excluded. Such spontaneous complete remissions, often associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors is discussed.