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Anaplastic lymphoma kinase–negative anaplastic large cell lymphoma (ALK– ALCL) is an aggressive neoplasm of T-cell/null-cell lineage. The T-Cell Project is a global prospective cohort study that consecutively enrolled patients newly diagnosed with peripheral T-cell lymphoma, registered through a centralized computer database between September 2006 and February 2018. Of 1553 validated cases from 74 sites in 13 countries worldwide, 235 were reported as ALK– ALCL. The median age at diagnosis was 54 years (range, 18-89 years), with a male predominance (62%). Stage III to IV disease was identified in 71% of patients, bulky disease and bone marrow involvement were uncommon, and 66% of patients presented with a low (0-1) International Prognostic Index score. Of all treated patients, 85% received multiagent initial chemotherapy, and 8% were consolidated with autologous hematopoietic cell transplantation. The initial overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months (95% confidence interval [CI], 41-63), the median progression-free survival (PFS) and overall survival (OS) were 41 months (95% CI, 17-62) and 55 months (95% CI, 36-75), respectively. The 3- and 5-year PFS rates were 52% and 43%, and the 3- and 5-year OS rates were 60% and 49%. Treatments containing both anthracycline and etoposide were associated with superior OS (P = .05) but not PFS (P = .18). In this large prospective cohort study, outcomes comparable to those previously reported in the retrospective International Peripheral T-Cell Lymphoma Project were observed. The study underscores the need for introducing novel platforms for ALK– ALCL and establishes a benchmark for future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT01142674.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare lymphoid malignancies that mostly have poor prognoses with currently available treatments. Upfront consolidation with autologous stem cell transplantation (ASCT) is frequently carried out, but its efficacy has never been investigated in randomized trials. We designed a multicenter, international, retrospective study with the main objective of comparing progression-free survival (PFS) and overall survival (OS) of patients with PTCL who underwent ASCT in complete remission (CR) after first-line chemotherapy with a control group who did not undergo ASCT. From the initial population of 286 registered patients, 174 patients with PTCL other than anaplastic large cell lymphoma, ALK-positive, deemed fit for ASCT at the time of diagnosis, and who were in CR or uncertain CR after induction therapy (CR1) were included in our analysis. 103 patients underwent ASCT, whereas 71 did not, in most cases (n=53) because the physician decided against it. With a median follow-up of 65.5 months, PFS was significantly better in the transplanted patients than in the non-transplanted group: 63% vs. 48% at 5 years (p=0.042). OS was significantly longer for ASCT patients in the subgroup with advanced stage at diagnosis (5-year OS: 70% vs. 50%, p=0.028). In the multivariate analysis, first-line ASCT was associated with significantly prolonged PFS (HR 0.57, 95% CI 0.35-0.93) and OS (HR 0.57, 95% CI 0.33-0.99). In conclusion, our study supports the use of ASCT as a consolidation strategy for patients with PTCL in CR1. These results should be confirmed in a prospective randomized study.

Purpose Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are rare and heterogeneous forms of non-Hodgkin's lymphoma (NHL) that, in general, are associated with a poor clinical outcome. Patients and Methods A cohort of 1,314 cases of PTCL and NKTCL was organized from 22 centers worldwide, consisting of patients with previously untreated PTCL or NKTCL who were diagnosed between 1990 and 2002. Tissue biopsies, immunophenotypic markers, molecular genetic studies, and clinical information from consecutive patients at each site were reviewed by panels of four expert hematopathologists and classified according to the WHO classification. Results A diagnosis of PTCL or NKTCL was confirmed in 1,153 (87.8%) of the cases. The most common subtypes were PTCL not otherwise specified (NOS; 25.9%), angioimmunoblastic type (18.5%), NKTCL (10.4%), and adult T-cell leukemia/lymphoma (ATLL; 9.6%). Misclassification occurred in 10.4% of the cases including Hodgkin's lymphoma (3%), B-cell lymphoma (1.4%), unclassifiable lymphoma (2.8%), or a diagnosis other than lymphoma (2.3%). We found marked variation in the frequency of the various subtypes by geographic region. The use of an anthracycline-containing regimen was not associated with an improved outcome in PTCL-NOS or angioimmunoblastic type, but was associated with an improved outcome in anaplastic large-cell lymphoma, ALK positive. Conclusion The WHO classification is useful for defining subtypes of PTCL and NKTCL. However, expert hematopathology review is important for accurate diagnosis. The clinical outcome for patients with most of these lymphoma subtypes is poor with standard therapies, and novel agents and new modalities are needed to improve survival.

Catalase-peroxidases are the only heme peroxidases with substantial hydrogen peroxide dismutation activity. In order to understand the role of the redox chemistry in their bifunctional activity, catalatically-active and inactive mutant proteins have been probed in spectroelectrochemical experiments. In detail, wildtype KatG from Synechocystis has been compared with variants with (i) disrupted KatG-typical adduct (Trp122-Tyr249-Met275), (ii) mutation of the catalytic distal His123-Arg119 pair, and (iii) altered accessibility to the heme cavity (Asp152, Ser335) and modified charge at the substrate channel entrance (Glu253). A valuable insight into the mechanism of reduction potential (E degrees') modulation in KatG has been obtained from the parameterization of the corresponding enthalpic and entropic components, determined from the analysis of the temperature dependence of E degrees'. Moreover, model structures of ferric and ferrous Synechocystis KatG have been computed and used as reference to analyze and discuss the experimental data. The results, discussed by reference to published resonance Raman data on the strength of the proximal iron-imidazole bond and catalytic properties, demonstrate that E degrees' of the Fe(III)/Fe(II) couple is not strongly correlated with the bifunctional activity. Besides the importance of an intact Trp-Tyr-Met adduct, it is the architecture of the long and constricted main channel that distinguishes KatGs from monofunctional peroxidases. An ordered matrix of oriented water dipoles is important for H2O2 oxidation. Its disruption results in modification of enthalpic and entropic contributions to E degrees' that reflect reduction-induced changes in polarity, electrostatics, continuity and accessibility of solvent to the metal center as well as alterations in solvent reorganization. (C) 2010 Elsevier Inc. All rights reserved.

Autologous stem-cell transplantation; Chemotherapy; T-cell lymphoma Trasplante autólogo de células madre; Quimioterapia; Linfoma de células T Trasplantament autòleg de cèl·lules mare; Quimioteràpia; Limfoma de cèl·lules T Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare lymphoid malignancies that mostly have poor prognoses with currently available treatments. Upfront consolidation with autologous stem cell transplantation (ASCT) is frequently carried out, but its efficacy has never been investigated in randomized trials. We designed a multicenter, international, retrospective study with the main objective of comparing progression-free survival and overall survival of patients with PTCL who underwent ASCT in complete remission (CR) after first-line chemotherapy with a control group who did not undergo ASCT. From the initial population of 286 registered patients, 174 patients with PTCL other than anaplastic large cell lymphoma, ALK-positive, deemed fit for ASCT at the time of diagnosis, and who were in CR or uncertain CR after induction therapy (CR1) were included in our analysis. one hundred and three patients underwent ASCT, whereas 71 did not, in most cases (n=53) because the physician decided against it. With a median follow-up of 65.5 months, progression-free survival was significantly better in the transplanted patients than in the non-transplanted group: 63% versus 48% at 5 years (P=0.042). Overall survival was significantly longer for ASCT patients in the subgroup with advanced stage at diagnosis (5-year overall survival: 70% vs. 50%, P=0.028). In the multivariate analysis, first-line ASCT was associated with significantly prolonged progression-free survival (HR=0.57, 95% CI: 0.35-0.93) and overall survival (HR=0.57, 95% CI: 0.33-0.99). In conclusion, our study supports the use of ASCT as a consolidation strategy for patients with PTCL in CR1. These results should be confirmed in a prospective randomized study.

Purpose Patients with follicular lymphoma (FL) registered in the F2-study and initially managed without treatment were analyzed to describe the presentation and outcome of a watch and wait (W&W) strategy in the rituximab era, to identify parameters for initiating treatment, and to evaluate whether initial W&W could have deleterious effects on treatment efficacy after progression or relapse. Patients and Methods Between 2003 and 2005, 120 patients selected from the 1,093 treatment-naive patients with FL in the F2-study cohort were initially managed expectantly (W&W), and 107 patients were assessed. Most of these patients (80%) had disseminated disease with a low tumor burden according to Groupe d'Etudes des Lymphomes Folliculaires criteria. Results After a median follow-up of 64 months, treatment was initiated in 54 patients (50%), with a median delay of 55 months for the entire cohort. In a univariate analysis, involvement of more than four nodal areas (hazard ratio [HR], 2.26) and serum albumin less than 3.5 g/dL (HR, 3.51) were predictive of a shorter time to lymphoma treatment initiation. In a multivariate analysis, only involvement of more than four nodal areas remained significant (HR, 2.32). The 4-year freedom from treatment failure (FFTF) rate of W&W patients (79%; 95% CI, 69% to 85%) was not inferior to that of a subgroup of 242 patients from the F2-study cohort with good prognosis characteristics who were initially treated with a rituximab-based regimen (69%; 95% CI, 61% to 76%; P = .103). Conclusion In the rituximab era, patients with FL in a selected prognostically favorable group can still be managed with W&W. W&W does not seem to have detrimental effects on FFTF and overall survival rates after treatment.

The impact of different treatment modalities and prognostic factors on the clinical course of primary thyroid diffuse large B-cell lymphoma (PTDLBCL) is still the subject of research. This study was conducted to clarify these clinical aspects of this disorder. The clinical parameters of 48 patients with PTDLBCL at time of diagnosis were comparable to those of previous studies. Patients underwent either radiotherapy (RT) ±° surgery (SX), chemotherapy (CHT) alone or in combination with local treatments (RT or SX), or SX followed by CHT and RT. A 90% complete remission (CR) rate was observed among patients who underwent combined treatment modalities (CTM), compared to 76% among the others. The 5-year progression-free survival differed significantly between both groups (p = 0.028). Poor performance status and advanced age correlated with decreased survival. PTDLBCL is a curable disease prevalent in elderly patients. Combined treatment modalities were able to induce an elevated rate of CR, improving long-term survival in younger patients. However, the outcome in elderly patients still remains unsatisfactory. © 2011 Informa UK, Ltd.