Clinical effectiveness of platelets in additive solution treated with two commercial pathogen-reduction technologies.

BACKGROUND: Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets. STUDY DESIGN AND METHODS: The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients. RESULTS: In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients. CONCLUSION: Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies.

Ultrasound point shear wave elastography assessment of liver and spleen stiffness: effect of training on repeatability of measurements.

OBJECTIVES: To evaluate reproducibility of measurements of spleen stiffness (SS) and liver stiffness (LS) at several sites by using point shear wave elastography (pSWE) and to investigate any training effect. METHODS: Healthy volunteers were consecutively enrolled. Measurements of SS and LS were performed by an expert (observer 1) and a novice (observer 2) at three different sites of liver and spleen. To assess the effect of training the study was conducted in two periods (period 1 and period 2). Concordance correlation coefficient was used to assess intra-observer and inter-observer reproducibility. RESULTS: A total of 92 subjects (67 men and 25 women) were enrolled in the study. Both intra-observer and inter-observer agreement were higher for the liver than for the spleen. Overall, the highest intra-observer and inter-observer agreement were obtained for the assessment of LS through intercostal space, and for measurements at this site there was a significantly better performance of observer 2 after the training period. For both observers, training improved the repeatability of SS measurements at all sites. A good intra-observer agreement was obtained only for measurements at the spleen lower pole. CONCLUSIONS: The results of this study show that a learning curve in pSWE acquisition should be taken into account both for SS and LS measurements. KEY POINTS: Reproducibility of SS measurements depends on the expertise of the operator. To achieve good reproducibility between measurements a training period is required. A learning curve in pSWE acquisition should be taken into account. SS measurements are less reproducible than LS measurements.

Best practice for peripheral blood progenitor cell mobilization and collection in adults and children: results of a Società Italiana Di Emaferesi e Manipolazione Cellulare (SIDEM) and Gruppo Italiano Trapianto Midollo Osseo (GITMO) consensus process.

BACKGROUND: A large heterogeneity in current mobilization and collection practices is perceived. Moreover, recent evidence introduced novel issues into some specific topics. Optimization of the clinical practice, through the adoption of clinical practice guidelines, previously proved to reduce health care resource use. STUDY DESIGN AND METHODS: Two Italian scientific societies, Società Italiana Di Emaferesi e Manipolazione Cellulare (SIDEM) and Gruppo Italiano Trapianto Midollo Osseo (GITMO), perceived the need of hematologists and transfusionists to share a common paradigm in the setting of hematopoietic stem cell transplantation (SCT). The aim of the current position paper is to provide common definitions and criteria for mobilization and collection of peripheral blood stem cells both in autologous and in the allogeneic setting. Current international and national standards (i.e., International Society of Hematotherapy and Graft Engineering) and recommendations (i.e., European Group for Blood and Marrow Transplantation) were harmonized with the Panel recommendations. RESULTS: The Expert Panel consisted of nine members (five transfusionists and four hematologists with both clinical and scientific experience of SCT in both pediatric and adult setting) and one methodologist and first convened on April 19, 2010: they in turn agreed on the questions to be answered by the project. Available literature was reviewed by one expert and the methodologist and presented to the other members. Statements were then formulated. SIDEM and GITMO planned an informal meeting of the Panel every 2 years to discuss relevant updates and possible changes to the recommendations. CONCLUSION: The efforts of the expert panel members allowed to set up and share a common approach to the mobilization, enumeration, and collection issues in the field of both autologous and allogeneic peripheral blood SCT.

The HLA alleles DRB1*13 and DQB1*06 are associated to Whipple's disease.

BACKGROUND & AIMS: Whipple's disease is a systemic, chronic, relapsing disorder caused by a combination of environmental (Tropheryma whipplei) and unknown host factors. Because it is a rare disease, the association between HLA type and Whipple's disease has been studied in only small numbers of patients; these studies have led to conflicting results. We aimed to investigate whether disease phenotype and outcome are associated with HLA type in 122 patients with Whipple's disease. METHODS: Genomic DNA was collected from 103 German, 11 Italian, and 8 Austrian patients with Whipple's disease, along with 62 healthy Austrian workers exposed to T whipplei (14 stool samples contained the bacterium). HLA class I and II alleles were identified by polymerase chain reaction analysis. Patient genotypes were compared with those of healthy German and Austrian populations; data for Italian controls were obtained from the Pavia HLA bone marrow donors' bank. RESULTS: HLA-DRB1*13 and DQB1*06 alleles occurred significantly more frequently in patients with Whipple's disease but not in healthy individuals who had been exposed to T Whipplei. The cumulative odds ratios for disease were 2.23 for the DRB1*13 allele (P < .0001) and 2.25 for the DQB1*06 allele (P < .0001). CONCLUSIONS: DRB1*13 and DQB1*06 alleles were found to be risk factors in the largest HLA study ever performed in patients with Whipple's disease.

Extracorporeal photochemotherapy in graft-versus-host disease: a longitudinal study on factors influencing the response and survival in pediatric patients.

BACKGROUND: Extracorporeal photochemotherapy (ECP) is a valid therapeutic option in the treatment of acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively). No standard clinical and laboratory criteria of response to ECP treatment are available at the moment. STUDY DESIGN AND METHODS: Clinical and laboratory variables on 73 pediatric patients with aGVHD (n = 50) and cGVHD (n = 23) were correlated with response to ECP and survival. RESULTS: An overall response (OR) was obtained in 34 of 50 (68%) aGVHD and in 16 of 23 (69.5%) cGVHD patients. Steroid tapering within 30 days of 1.3 mg/kg in OR (p = 0.004) was the sole highly significant correlation with response found in aGVHD while no correlation emerged for cGVHD (p = 0.28). Among aGVHD patients, response to ECP was inversely associated with death: among OR, deaths were 13 of 34 (38.2%), while among nonresponders, deaths were 15 of 16 (93.8%; p < 0.001). On the other hand, decrease of steroid dose at 30 days was associated with survival: for each 1 mg/kg reduction, the hazard ratio was 2.2, and the 95% confidence interval was 1.5 to 3.2 (p < 0.001). No other clinical or laboratory variables statistically associated with survival were found. CONCLUSIONS: Our results demonstrate that steroid tapering within the first 30 days of ECP treatment in aGVHD and response to ECP in acute and chronic GVHD are the only variables influencing response and survival, respectively.

Daily plasma-exchange for life-threatening class I HELLP syndrome with prevalent pulmonary involvement.

HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) is a thrombotic microangiopathy affecting a minority of women with pre-eclampsia and usually resolves after delivery. The role of plasma exchange in HELLP syndrome has to be defined. Herein is reported a case of a primipara with a class I HELLP syndrome with prevalent pulmonary involvement successfully treated with 8 consecutive plasma exchange plus corticosteroids. In class I HELLP syndrome with cardiopulmonary complications early plasma exchange could be considered a therapeutic option.

Immunomagnetic cell selection performed for HLA haploidentical transplants with the CliniMACS device: effect of additional platelet removal on CD34+ cell recovery.

Immunomagnetic CD34+ cell selection (ICS) is a widely employed technology in autotransplant and allotransplant settings. When an haploidentical transplant is performed, a high dose of purified CD34+ cells together with efficient T and B cell depletion are required to minimize the risks of graft versus host disease (GVHD) and Epstein-Barr virus (EBV)-related lymphoma. To ameliorate the performances of the CliniMACS (Miltenyi Biotec) ICS device, we compared 73 ICS performed following the manufacturer's recommended platelet depletion versus 48 performed after adjunctive centrifugations to increase platelet depletion of the leukapheresis (LKF) product. A total of 121 ICS (from single or fractioned LKF products) were carried out on 93 LKF collected from 47 related healthy donors. A statistical significance in terms of CD34+ cell recovery (81.8% vs. 71.2%) was found in favor of the modified ICS procedure (p=0.0049) with a comparable stem cell purity and viability. The modification of the standard manufacturer's technique for increasing platelet depletion can further improve the recovery of stem cells with no influence on T and B cell depletion. These results demonstrate the negative influence exerted on CD34+ cell recovery by LKF platelet contamination.

Parental GM and HLA genotypes and reduced birth weight in patients with Turner's syndrome.

We investigated a possible influence on birth weight in Turner's syndrome of many clinical, hormonal, genetic and immunogenetic variables. We considered 97 patients with Turner's syndrome. Patients with parents with identical GM (Gamma heavy chains Marker) phenotype had a significantly lower birth weight than those with parents with different GM phenotype. Karyotype other than 45,X, HLA (Human Leukocyte Antigen) parental sharing, mother-patient compatibility and elevated 17-hydroxyprogesterone (17OHP) serum level after adrenocorticotropin hormone (ACTH) and absence of heart and kidney malformations and lymphedema were associated with a lower birth weight, but not significantly. Multiple interactions showed that the presence of an identical GM phenotype in parents, together with other conditions (karyotype other than 45,X, adrenal dysfunction, HLA parental sharing, mother-child compatibility, KM(3) [Kappa light chains Marker] phenotype) resulted in a further decrease of birth weight. These data might suggest a negative effect of genetic similarity on intrauterine growth in Turner's syndrome.

Interobserver reproducibility of the controlled attenuation parameter (CAP) for quantifying liver steatosis.

PURPOSE: This study was conducted to prospectively investigate the interobserver reproducibility of controlled attenuation parameter (CAP) measurements and the relationship among the CAP and body mass index (BMI), gender and age. METHODS: Consecutive subjects were studied using the M+ probe of the FibroScan device (Echosens, Paris, France). Measurements were performed by two raters (rater1 and rater2). Interobserver agreement was assessed by using the concordance correlation coefficient (CCC). The Pearson r coefficient was used to test correlation between two study variables, and linear regression was used for the multivariate model. RESULTS: Three hundred fifty-one subjects (227 males and 124 females) were prospectively studied. The CCC was 0.82 (95 % CI 0.78-0.85) overall, 0.80 (95 % CI 0.75-0.85) for BMI <25 kg/m(2), 0.76 (95 % CI 0.69-0.84) for BMI 25-29 kg/m(2) and 0.65 (95 % CI 0.41-0.88) for BMI ≥30 kg/m(2). The CCC was 0.44 (95 % CI 0.31-0.56) for CAP values ≤240 dB/m and 0.72 (95 % CI 0.65-0.79) for CAP values >240 dB/m. In univariate analysis, age and BMI by gender were correlated with the CAP. Multiple regression analysis confirmed the relationship of the CAP with age and BMI, but not with gender. CONCLUSIONS: The results of this study show that the interreader agreement in CAP measurement is good. In healthy volunteers, the CAP is strongly correlated with age and BMI.