Search

Background and purpose: There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. Methods: Patients with relapsing–remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. Results: A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. Conclusions: The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described. [ABSTRACT FROM AUTHOR]

Background: The Italian Registry of Laparoscopic Surgery of the Spleen (IRLSS) was developed to provide at the national level an informative tool useful for performing multicenter studies in the field of spleen laparoscopic surgery. In this first study analyzing the IRLSS data, a cohort of patients with hematologic diseases was retrospectively investigated for potential predictive parameters that could affect the outcome of laparoscopic splenectomy.Methods: A total of 309 patients who underwent laparoscopic splenectomy for hematologic diseases in 17 Italian centers (between February 1, 1993, and September 30, 2004) were entered in the IRLSS. Their records were analyzed retrospectively by the Student's t-test, chi-square, and logistic regression.Results: The mean operative time was 141 min (range, 30-420 min). Conversion was necessary in 21 cases (7%), and approximately 1 accessory spleen in 25 patients (9%) was found. The mean spleen weight was 1191 g (range, 85-4,500 g). Perioperative death occurred in two cases (0.6%). No complications were experienced by 253 patients (81.9%), who had a mean hospital stay of 5.4 days (range, 2-30 days). Overall morbidity occurred in 56 patients (18.1%), mainly associated with transient fever (n = 22), pleural effusion (n = 13), and actual or suspected hemorrhage (n = 12), requiring a reintervention for 7 patients. Multivariate analysis found that body mass index (p = 0.024) and clinical indication (p = 0.004) were independent predictors for surgical conversion. The clinical indication was almost significant as an independent predictor for the occurrence of postoperative complication (p = 0.05).Conclusions: This first study analyzing the IRLSS data shows that laparoscopic splenectomy may represent the gold standard treatment for hematologic diseases with normal-size spleen. The low morbidity and mortality rate suggests that laparoscopic splenectomy can be successfully proposed also for splenomegaly in hematologic malignancies. [ABSTRACT FROM AUTHOR]

Background: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase., Objectives: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008., Methods: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months., Results: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression., Conclusions: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

Objectives: Renal dysfunction is a common complication in human immunodeficiency virus (HIV)-infected patients and can be attributed to direct viral damage, comorbidities or drug toxicity. The aim of this study was to assess cross-sectional correlates of renal damage in a contemporary European cohort of patients., Methods: We performed a case-control study from our cohort of 750 HIV-infected adults over a period of 5 months. We assessed renal damage by either proteinuria (≥+ on urine dipstick), reduced creatinine clearance (< 60 ml/min) or reduced estimated glomerular filtration rate (eGFR) of < 60 ml/ min/1.73 m2. The characteristics of cases and controls were compared in analysis and in multivariate logistic regression models with stepwise selection., Results: Approximately 50% of the screened 106 patients had a qualifying abnormality. Altogether, we identified 55 cases with 110 age- and gender-matched controls. Mean eGFR was 90.7 (4.8) for cases vs. 106.1 (2.3) ml/min/1.73 m2 for controls (p = 0.001). Cases had a longer duration of HIV infection, more complex regimen, longer exposure to antiretroviral therapy and a more frequent diagnosis of acquired immune-deficiency syndrome (AIDS) and hepatitis C virus (HCV) infection. In the logistic multivariate model, renal damage remained significantly associated with longer known duration of HIV infection (OR 2.88, 95% CI: 1.28 - 6.46, p = 0.01), AIDS defining condition (OR 1.09 95% CI: 1.03 - 1.16, p = 0.002) female gender (OR 2.01, 95% CI: 0.96 - 4.18, p = 0.06), and HCV infection (OR 2.12, 95% CI: 0.99 - 4.52, p = 0.05)., Conclusions: Duration, antiretroviral regimen and coincidental HCV impacted the frequency of renal abnormalities in our patients.

The importance of HLA donor-recipient matching in unrelated haematopoietic SCT (HSCT) is the subject of debate. In this retrospective study, we analyzed 805 adult patients from the Italian Registry receiving HSCT for a haematological malignancy from January 1999 to June 2006 and correlated the degree of HLA matching with transplant outcome. All patient-donor pairs had high-resolution typing at HLA-A, -B, -C, -DRB1 and -DQB1. There was a significantly higher risk of overall mortality, non-relapse mortality, graft failure and acute GVHD (aGVHD) for patients receiving HSCT from an unrelated donor with one or more low- or high-resolution mismatch/es (Mm/s). When only a single HLA Mm is present (9/10 matched pairs), mortality risk is higher than among 10/10 matched pairs in patients transplanted with acute leukaemia in the first CR ('early' patients) but not in the other patients (advanced patients): HR=1.69, 95% CI=0.94-3.02, P=0.08; HR=1.03, 95% CI=0.80-1.32, P=0.82, for early and advanced patients, respectively. These results confirm that the advantage of a 10/10 match has a greater effect in early patients, thus suggesting that a 9/10 matched donor can be chosen in patients with advanced disease lacking a rapidly available 10/10 matched one.

Purpose: Identification of new enhancing lesions is a major endpoint of longitudinal brain magnetic resonance (MR) studies of multiple sclerosis (MS). To date, this is a visual, time-consuming procedure. We present here a supervised automated procedure (SAP) aimed at reducing the time needed to identify new MS enhancing lesions., Materials and Methods: The SAP uses an algorithm including Cartesian coordinates of the lesions to be compared, their area and a constant (k). The procedure was validated for enhancing lesions on T1-weighted spin-echo images after intravenous administration of 0.1 mmol/kg of paramagnetic contrast agent, randomly selected from a dataset of a longitudinal MR study on ten relapsing-remitting MS patients followed for 2-5 years. During the validation session, two readers decided by consensus whether two lesions, present on the same slice of two examinations performed on subsequent dates, were the same or not. In this way, k was calibrated to obtain the same result from both visual inspection and automatic algorithm output., Results: After evaluating of 25+/-5 (mean+/-standard deviation) lesions in each of ten different sessions with correction of k value, the k value became a stable value (0.45+/-0.05)., Conclusions: Once the suitable value of k was found, SAP was able to identify new enhancing lesions, avoiding visual inspection, which is usually a lengthy procedure.

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.