A multicenter retrospective clinical study of CD5/CD10-negative chronic B cell leukemias.

CD5-negative chronic B cell lymphoproliferative disorders in leukemic phase (B-CLPD) are heterogeneous and relatively uncommon pathologies that often lack a histopathological definition because of the absence of accessible pathological tissue. We describe the clinical features and evolution-related variables of 156 patients with CD5/CD10-negative B-CLPD (median age 66 years, range 25-86). The median follow-up was 51 months (range 6-216), and overall 3- and 5-year survival was respectively 87 and 76%; 50 patients needed therapy at diagnosis, 56 during follow-up, and 50 remained untreated until the last control. A combined clinical, histological, cytomorphological, immunophenotypical, and cytogenetic diagnostic approach allowed the complete classification of only a minority of patients as being affected by splenic marginal zone or lymphoplasmacytic lymphoma; the majority of cases remained unclassifiable. Multivariate analysis showed that the clinicohematological variables adversely related to overall survival were serum LDH levels and age, whereas high serum LDH levels, hemoglobin levels of <11 g/dl, and splenomegaly related to treatment-free time (in "wait and see" cases); only splenomegaly related to time to progression (in treated patients). In conclusion, our retrospective study describes the clinical features and variables related to evolution in a large group of patients with CD5/CD10-negative chronic B-cell lymphoid leukemias and underlines the fact that a probable lymphoplasmacytic or marginal zone normal cell origin can be supposed in such leukemic forms, but never surely demonstrated

Diagnostic role and prognostic significance of a simplified immunophenotypic classification of mature B cell chronic lymphoid leukemias

We verified the diagnostic and prognostic role of a simplified immunophenotypic classification (IC) in a series of 258 patients (M/F: 1.4; median age: 64 years; median follow-up: 64 months; 75 deaths) with mature B cell lymphoid leukemias (MBC-LL) for whom no histopathological diagnosis was available because of minimal or no lymph node involvement. The IC was based on the reactivity of three pivotal immunophenotypic markers: CD5, CD23 and SIg intensity. On the basis of different expression patterns, we identified four diagnostic clusters (C) characterized by distinct clinico-biological features and different prognoses: C1 (149 patients) identified most classical B cell chronic lymphocytic leukemias (CLL-type cluster; SIg(dim)/CD5+/CD23+); C2, 38 patients whose clinico-hematological characteristics were intermediate between C1 and C3 (CLL-variant cluster; SIg(bright)/CD5+/CD23+/-or SIg(dim)/CD5-/-/CD23 indifferent); C3 (16 patients) most situations consistent with mantle cell lymphoma in leukemic phase (MCL-type cluster; SIg(bright)/CD5+/CD23-); and C4, 55 cases, most of whom were consistent with leukemic phase lymphoplasmacytic/splenic marginal zone lymphomas (LP/S-type cluster; SIg(bright)/CD5-/+/CD23 indifferent). At univariate survival analysis, prognosis worsened from C1 to C4, C2 and C3 (P = 0.0001), and this was maintained at multivariate analysis (P = 0.006), together with CD11c expression (P = 0.0043), age at diagnosis (cut-off 70 years; P = 0.0008) and platelet count (cut-off 140 x 10(9)/l; P = 0.0034). Besides recognising the two well-known situations of classic B-CLL and MCL, our IC identified situations with distinct prognostic and/or clinical behaviors

Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping

Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files—B-cell chronic lymphocytic leukemias (B-CLL; n=10), mantle cell (MCL; n=10) and follicular lymphomas (FL; n=10)—were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels

Analisi e modellizzazione dell&apos;effetto di agrotecniche sull&apos;altezza della pianta : il progetto MIATA

L\u2019altezza delle piante \ue8 importante per determinarne il potenziale produttivo e la suscettibilit\ue0 nei confronti di avversit\ue0 abio-tiche. Nonostante questo, i modelli disponibili la ignorano o la simulano utilizzando semplici funzioni logistiche indipendenti dai reali processi bioLsici in gioco e dalle modalit\ue0 di gestione. Il progetto MIATA, condotto da studenti del corso di Sistemi Colturali dell\u2019Universit\ue0 degli Studi di Milano, ha affrontato la problematica, fornendo soluzioni modellistiche utili sia a scopo previsionale che di supporto alla gestione

Italian real life experience with brentuximab vedotin : results of a large observational study on 234 relapsed/refractory Hodgkin&apos;s lymphoma

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity.Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients

The kinetic modeling of soot precursors in ethylene flames

A comprehensive, semidetailed kinetic scheme describing hydrocarbon oxidation is applied to the simulation of premixed, rich, sooting, ethylene laminar flames. The main goal of this work is to investigate the soot precursor and aromatic pathways under different operative conditions in terms of temperatures and feed composition. The modeling computations are in good agreement with the experimental data and are also comparable with predictions of different kinetic schemes present in the literature. The recombination reactions of resonantly stabilized radicals (such as propargyl) and C2H2 addition on linear dehydrogenated molecules (C4Hx) are taken into account to explain formation of the first aromatic ring. Two major channels of benzene and polycyclic aromatic hydrocarbon (PAH) formation are observed in the conditions under analysis. The former, which is not included in previous literature schemes, is faster and occurs first (where the conversion is still low). It is governed by ethylene and vinyl radical, which, through butadiene and butenyl radicals, explain the formation of cyclopentadiene and through further successive additions give rise to benzene and styrene. This mechanism should be the starting point for the initial formation of heavy highly hydrogenated compounds. Acetylene and resonantly stabilized radicals are mainly responsible for the successive aromatic growth. The study of such pathways is also important for the analysis of low NOx burners and new process alternatives, such as recirculating flue gases, where pollutant emission reductions are pursued by the use of low-temperature flames. The comparisons with experimental data for pure ethylene pyrolysis at lower temperatures (1100 K) confirms the validity of the assumed mechanism

Prognostic factors in symptomatic Waldenstrom's macroglobulinemia

We analyze the prognostic value of the presenting features of a series of patients with symptomatic Waldenstrom's macroglobulinemia who were homogeneously treated. A total of 215 patients (119 males) with a median age of 62.6 years (range, 24.9 to 91.6) were retrospectively analyzed. The median overall follow-up was 57.6 months (range, 0.6 to 281): 58 (0.9 to 281) for living patients and 52.2 (0.6 to 261.3) for those who died. All patients were treated with alkylating agent-based chemotherapy. The overall median survival was 77.2 months, without significant differences based on the duration of the previous monoclonal gammopathy of undetermined significance (MGUS) phase. The multivariate Cox analysis performed on the whole population showed that age, hemoglobin level, and serum albumin level predicted survival. The addition of beta(2)-microglobulin, available in the subgroup of 60 patients diagnosed after 1990, in a Cox stepwise selection showed that this parameter was by far the main prognostic determinant. Application of the Dhodapkar, Morel, and Gobbi scoring systems to this population of patients showed that all three stratified the population into groups with significantly distinct prognoses. A prognostic index based on age, hemoglobin, and albumin is capable of identifying various groups of patients with different therapeutic needs