Franca Soldano

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 x 10(9)/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m(2) rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count > or = 50 x 10(9)/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, -0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, -0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

Contrast-Enhanced Breast MRI in Patients with Suspicious Microcalcifications on Mammography: Results of a Multicenter Trial

OBJECTIVE The objective of our study was to test dynamic MRI in evaluating mammographically detected suspicious microcalcifications. MATERIALS AND METHODS One hundred twelve patients with mammographically detected microcalcifications with BI-RADS category 5 (n = 78) or 4 (n = 34) lesions were studied at 17 centers a using 3D gradient-echo dynamic coronal technique (< or = 3 mm thickness) and 0.1 mmol/kg of gadoteridol. A pathologic sample was obtained in all cases. Agreement between the major diameter measured on mammography, MRI, or both and the major diameter measured at pathologic examination was calculated in 62 cases. RESULTS Of the 112 lesions, pathologic examination revealed 37 benign lesions, 33 ductal carcinoma in situ (DCIS), and 42 invasive carcinomas. The specificity of MRI for benign lesions was 68%. Considering the subgroups of calcifications alone and calcifications associated with masses, the specificity values became 79% and 33%, respectively. The sensitivity of MRI for DCIS was 79%. Analysis of the two subgroups showed sensitivity values of 68% for calcifications alone and of 1% for calcifications associated with masses. The sensitivity for invasive carcinomas was 93%. Analysis of the two subgroups showed sensitivity values to be 92% for calcifications alone and 94% for calcifications associated with masses. Considering the overall results, the sensitivity of MRI was 87%; specificity, 68%; positive predictive value, 84%; negative predictive value, 71%; and accuracy, 80%. Considering the subgroups of calcifications alone and calcifications associated with masses, the sensitivity values became 80% and 97%; the positive predictive values, 86% and 82%; the negative predictive values, 71% and 75% (95% confidence interval [CI], 0.19-0.99); and the accuracy values, 80% and 82% (95% CI, 0.66-0.92), respectively. An odds ratio (OR) of 13.54 (95% CI, 5.20-35.28) showed a raised risk of malignant breast tumor in subjects with positive MR examination of mammographically detected suspicious clusters of microcalcifications. The statistical analysis on each subgroup showed an OR of 15.07 (95% CI, 4.73-48.08) for calcifications alone and an OR of 14.00 (95% CI, 1.23-158.84) for calcifications associated with masses. Any significant improvement in the predictive ability of dynamic MRI depending on the extent of calcifications on mammography was not proved. Considering the 62 cases of proved malignancy with measured maximal diameter at pathologic examination, both mammography and MR examination seem to overestimate tumor extent. CONCLUSION The not-perfect sensitivity of MRI (87%), when applying our interpretation criteria and imaging sequences, is a crucial point that prevents us from clinical use of MRI in the diagnosis of mammographically detected microcalcifications.

Relevance of b‐values in evaluating liver fibrosis: A study in healthy and cirrhotic subjects using two single‐shot spin‐echo echo‐planar diffusion‐weighted sequences

To investigate the relevance of increasing b‐values in evaluating liver fibrosis through the agreement of two diffusion‐weighted (DW) sequences.

Diffusion-weighted MRI in evaluating liver fibrosis: a feasibility study in cirrhotic patients.

AbstractPurpose.This study was designed to establish whether the measurement of apparent diffusion coefficients (ADCs) is clinically accurate in diagnosing liver fibrosis in a selected series of cirrhotic patients.Materials and methods.Twenty-eight cirrhotic patients (mean age 58.1 years) with histologically proven liver fibrosis and 29 healthy controls (mean age 43.8 yeas) underwent liver diffusion-weighted magnetic resonance (MR) using a 1.5-Tesla (T) magnet equipped with a phased-array coil. Diffusion studies with parallel imaging [generalized autocalibrating partially parallel acquisitions (GRAPPA)] were performed within a single breath-hold using a single-shot spin-echo echo-planar sequence (TE 74 ms) using four b values: b=0, 150, 250 and 400 s/mm2. A unidirectional diffusion gradient was applied. ADCs were measured on ADC maps.Results.Mean ADC was significantly lower in cirrhotic livers than in controls (1.11±0.16 vs. 1.54±0.12.10-3mm2/s) (p<0.0001). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.96 [confidence interval (CI) 95%:(0.87; 0.94)], demonstrating higher sensitivity and specificity (92.9% and 100%, respectively) for an ADC cutoff of 1.31.10-3mm2/s. Positive predictive value (PPV), negative predictive value (NPV) and overall accuracy were 100%, 99.9% and 96.4%, respectively.Conclusions.Diffusion-weighted MRI is an accurate tool in evaluating advanced liver fibrosis if an optimised single-shot spinecho echo-planar sequence with maximum intermediate b value is used. The ADC threshold for liver fibrosis was 1.31.10-3mm2/s.

Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Rituximab 375 mg/m2 weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50×109/L) and complete responses (platelet count > 100×109/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3–18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose.

Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

In this GITMO study, Patriarca and coworkers evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors. They conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. See related perspective article on page 1449. Background Allogeneic stem cell transplantation is a potentially curative treatment for myelofibrosis, although its use is limited by a high rate of transplant-related mortality. In this study, we evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors. Design and Methods One hundred patients were transplanted in 26 Italian centers between 1986 and 2006. We analyzed the influence of the patients’ characteristics and the clnical features of their disease before stem cell transplantation and of transplant procedures on transplant-related mortality, overall survival, and relapse-free survival by means of univariate and multivariate analyses. Results The median age of the patients at the time of stem cell transplantation was 49 years (range, 21–68) and 90% of them had an intermediate or high Dupriez score. Forty-eight percent received a myeloablative conditioning regimen and 78% received stem cells from matched sibling donors. The cumulative incidence of engraftment at day 90 after transplant was 87% (95% CI, 0.87–0.97). The cumulative 1-year and 3-year incidences of transplant-related mortality were 35% and 43%, respectively. The estimated 3-year overall and relapse-free survival rates after stem cell transplantation were 42% and 35%, respectively. In multivariate analysis, negative predictors of transplant-related mortality were year of stem cell transplantation before 1995, unrelated donor, and a long interval between diagnosis and transplantation. There was a trend towards longer overall and relapse-free survival in patients receiving peripheral blood stem cells rather than bone marrow as the source of their graft (p=0.070 and p=0.077, respectively). The intensity of the conditioning regimen (myeloablative versus reduced intensity regimens) did not significantly influence the outcome. Conclusions We conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. We observed that a reduction in transplant-related mortality was associated with the choice of a matched sibling donor, whereas longer overall survival was associated with the use of peripheral blood as the source of stem cells.

Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results

Objective:  To evaluate the long‐term activity and toxicity profile of rituximab in adult patients with idiopathic immune thrombocytopenic purpura (ITP).

Descriptive Epidemiology of Head Injury in Romagna and Trentino

We studied the occurrence of head injury in two different Italian regions: Romagna and Trentino. Both geographical areas attract large numbers of seasonal tourists. The study was carried out over 1 year (January 1, 1998 to December 31, 1998), prospectively in Romagna and retrospectively in Trentino because of their different head injury management protocols. The study was based on all admissions to hospital extracted by medical staff from the case records, and all cases were identified by the ICD-9 codes (ranges: 800.0–800.3, 801.0–801.3, 803.0–803.3, 850, 851.0–851.1, 852.0–852.1, 853.0–853.1, 854.0–854.1). The annual incidence of hospitalization for head injury was 314/100,000, 297 for Romagna and 332 for Trentino. The causes of head trauma and the type of injuries were similar to those reported in the international literature, and so were the characteristics of the population at risk. Romagna recorded a higher incidence of head injury among the elderly, probably due to the widespread use of bicycles without safety helmets. In Romagna, where neurosurgery departments exist, hospital mortality was low (8/100,000/year). Based on similar international literature findings, different prevention measures are suggested to reduce the occurrence and severity of head injury.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (LT) is usually reserved for Child B and C patients with single or multiple nodules. The aim of this study was to compare HR and LT for HCC within the Milan criteria on an intention‐to‐treat basis. Forty‐eight patients were treated by LT and 38 by HR. The median time on the waiting list for transplantation was 118 days. The estimated overall survival was significantly higher (P = 0.005) in the LT group than in the HR one. The estimated freedom from recurrence was also significantly higher (P < 0.0001) for LT patients than for HR ones. Indeed, the probability of HCC recurrence after resection was higher than after transplantation achieving 31% and 76% for HR and 2% and 2% for LT at 3 and 5 years after surgery. Multivariate analysis confirmed that transplantation was superior to resection in terms of patient’s survival and risk of HCC recurrence. We conclude that LT is superior to HR for small HCC in cirrhotic patients assuming that LT should be performed within 6–10 months after listing to reduce the dropouts for reasons of tumor progression.

STEATOSIS OF THE HEPATIC GRAFT AS A RISK FACTOR FOR POST-TRANSPLANT BILIARY COMPLICATIONS

Baccarani U, Isola M, Adani GL, Avellini C, Lorenzin D, Rossetto A, Currò G, Comuzzi C, Toniutto P, Risaliti A, Soldano F, Bresadola V, De Anna D, Bresadola F. Steatosis of the hepatic graft as a risk factor for post‐transplant biliary complications.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01128.x.
© 2009 John Wiley & Sons A/S.