Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell'Adulto Multiple Myeloma Working Party study

INTRODUCTION: A still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called "poor-mobilizers" are difficult to be predicted, due to marked difference across previous heterogeneous studies. METHODS: We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (<2 710(6)/kg) or sub-optimal (<5 710(6)/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1,348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization. RESULTS: Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes. CONCLUSIONS: We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and may contribute to the early identification of "poor mobilizer" phenotypes

Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell'Adulto Multiple Myeloma Working Party study

Introduction: A still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called "poor-mobilizers" are difficult to be predicted, due to marked difference across previous heterogeneous studies.Methods: We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (&lt;2 x 10(6)/kg) or sub-optimal (&lt;5 x 10(6)/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1,348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization.Results: Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes.Conclusions: We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and may contribute to the early identification of "poor mobilizer" phenotypes

Mutational spectrum and clinical signatures in 114 families with hereditary multiple osteochondromas: insights into molecular properties of selected exostosin variants

Hereditary multiple osteochondromas (HMO) is a rare autosomal dominant skeletal disorder, caused by heterozygous variants in either EXT1 or EXT2, which encode proteins involved in the biogenesis of heparan sulphate. Pathogenesis and genotype-phenotype correlations remain poorly understood. We studied 114 HMO families (158 affected individuals) with causative EXT1 or EXT2 variants identified by Sanger sequencing, or MLPA and qPCR. Eighty-seven disease-causative variants (55 novel and 32 known) were identified including frameshift (42%), nonsense (32%), missense (11%), splicing (10%) variants and genomic rearrangements (5%). Informative clinical features were available for 42 EXT1 and 27 EXT2 subjects. Osteochondromas were more frequent in EXT1 as compared to EXT2 patients. Anatomical distribution of lesions showed significant differences based on causative gene. Microscopy analysis for selected EXT1 and EXT2 variants verified that EXT1 and EXT2 mutants failed to co-localize each other and loss Golgi localization by surrounding the nucleus and/or assuming a diffuse intracellular distribution. In a cell viability study, cells expressing EXT1 and EXT2 mutants proliferated more slowly than cells expressing wild-type proteins. This confirms the physiological relevance of EXT1 and EXT2 Golgi co-localization, and the key role of these proteins in the cell cycle. Taken together, our data expand genotype-phenotype correlations, offer further insights in the pathogenesis of HMO and open the path to future therapies

Diagnostic delay in adult coeliac disease: An Italian multicentre study

Background: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD). Aims: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD. Methods: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted. Results: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay. Conclusion: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented

Measurement of the polarization of the Xi0 (anti-Xi0) hyperon beam by the NA48/1 experiment

A total of 368415 Xi(0) --> Lambda Xi(0) and 31 171 (Xi(0)) over bar --> (Lambda) over bar pi(0) were selected from data recorded in the NA48/1 experiment during 2002 data taking. From this sample, the polarization of Xi(0) and (Xi(0)) over bar hyperons was measured to be P(Xi 0) = -0.102 +/- 0.012(stat) +/- 0.008(syst) and P((Xi 0) over bar) = -0.01 +/- 0.04(stat) 0.008(syst). The dependence of P(Xi 0) on the Xi(0) transverse momentum with respect to the primary proton beam is also presented. With the same data sample. the ratio of (Xi(0)) over bar and Xi(0) fluxes in proton collisions at 400 GeV/c oil a beryllium target was measure

New high statistics measurement of K-e4 decay form factors and pi pi scattering phase shifts

We report results from a new measurement of the K-e4 decay K-+/- -> pi(+)pi(-)e(+/-)nu by the NA48/2 collaboration at the CERN SPS, based on a partial sample of more than 670 000 K-e4 decays in both charged modes collected in 2003. The form factors of the hadronic current (F,G,H) and pi pi phase difference (delta=delta(s)-delta(p)) have been measured in ten independent bins of the pi pi mass spectrum to investigate their variation. A sizeable acceptance at large pi pi mass, a low background and a very good resolution contribute to an improved experimental accuracy, a factor two better than in the previous measurement, when extracting the pi pi scattering lengths a(0) (0) and a(0) (2). Under the assumption of isospin symmetry and using numerical solutions of the Roy equations, the following values are obtained in the plane (a(0) (0),a(0) (2)): a(0) (0)=0.233 +/- 0.016(stat)+/- 0.007(syst),a(0) (2)=-0.0471 +/- 0.011(stat)+/- 0.004syst. The presence of potentially large isospin effects is also considered and will allow comparison with precise predictions from Chiral Perturbation Theory

A new measurement of the K-+/- -> pi(+/-)gamma gamma decay at the NA48/2 experiment

The NA48/2 experiment at CERN collected two data samples with minimum bias trigger conditions in 2003 and 2004. A measurement of the rate and dynamic properties of the rare decay K-+/- -> pi(+/-)gamma gamma from these data sets based on 149 decay candidates with an estimated background of 15.5 +/- 0.7 events is reported. The model-independent branching ratio in the kinematic range z = (m(gamma gamma)/m(K))(2) > 0.2 is measured to be B-MI(z > 0.2) = (0.877 +/- 0.089) x 10(-6), and the branching ratio in the full kinematic range assuming a particular Chiral Perturbation Theory description to be B(K-pi gamma gamma) = (0.910 +/- 0.075) x 10(-6). (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)