Harmonization Project Research Articles

Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b Keynote-013 Study

Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b Keynote-013 Study

Prognostic Value of End of Treatment FDG-PET Scan in T-Cell Lymphoma, a 20-Year Single Institution Study

T-cell lymphomas represent a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs) characterized by dismal prognosis. Current first line chemotherapeutic approaches have not significantly changed during the last 20 years, and several efforts have been made for early risk stratification of T-cell NHL patients with unsatisfactory results. Functional imaging with 2-deoxy-2-[fluorine-18]fluoro- D-glucose positron emission tomography scan (FGD-PET) has demonstrated improved outcome stratification and response evaluation in Hodgkin lymphoma and B-cell NHL, in comparison with computed tomography (CT) scan. Most T-cell lymphomas are FDG avid and FDG-PET is routinely used in clinical practice, however limited and conflicting data are available on the value of FDG-PET in response assessment at the end of treatment (FDG-PETend). With the aim of evaluating the prognostic value of FDG-PETend in T-cell lymphomas we performed a retrospective study evaluating all T-cell NHL patients treated at the European Institute of Oncology (IEO, Milan) over the past 20 years. Clinical data of all T-cell NHL patients treated at IEO from 1995 to 2015 were retrospectively collected. The back bone of first line therapy did not significantly change over time, being based on the administration of CHOP/CHOP-like chemotherapy eventually followed by treatment intensification with autologous stem cell transplantation (ASCT). Post first-line therapy FDG-PET scans were visually evaluated according to the criteria of the international Harmonization Project (positive vs negative). Ninety-eight consecutive patients (58 males, 40 females) with complete clinical data were considered in this analysis. FDG-PET was used for response evaluation starting from 2002, but only 18 patients considered in the present analysis were treated before 2002. Median age at diagnosis was 54 years (range 14-82). Fifty-two patients (53.1%) had Peripheral T-cell lymphomas not otherwise specified (PTCL-NOS), 23 (23.5%) had anaplastic large T-cell lymphoma (ALCL), 15 (15.3%) had acute lymphoblastic T-cell lymphoma (LAL-T), 8 (8.1%) had NK/T-cell lymphoma. Ten patients were diagnosed in stage I, 21 in stage II, 17 in stage III, 50 patients in stage IV. Thirty-two patients underwent ASCT during the study period. Median follow-up was 16 months (range 1-182). 42 patients were evaluated with FDG-PET at the end of first line therapy: 25 had negative (60%), and 17 (40%) positive PET scans. In 56 patients response was evaluated with CT scan only, and complete responses or complete responses unconfirmed (CR/CRu) were detected in 29 cases (51%). The 10-year progression free survival (PFS) and overall survival (OS) of the whole patient cohort were 22% and 32% respectively. To determine the prognostic value of FDG-PETend we first assessed the PFS of PET positive vs PET negative patients. Those patients who were PET positive at the end of treatment had a statistically inferior PFS compared to PET negative ones (5-year PFS: 29% vs 47% respectively; p<0.01). These data indicate that although a negative PET after initial therapy is a good prognostic predictor, about half of all patients still relapse after achievement of a negative PET. To better define the prognostic value of FDG-PETend scan in T-cell lymphomas, we restricted our analysis to those patients who obtained a CR after first line therapy, comparing the outcome of PET negative patients (n=25) with the outcome of patients who did not have a PET scan but were deemed in CR after a negative CT scan (n=17). Interestingly we did not observe significant differences between the 2 groups (5-year PFS was 47% in both groups). These data were also confirmed when the analysis was restricted to the PTCL-NOS and ALCL subgroups, suggesting unsatisfactory improvements in the quality of CR assessment with a limited negative predictive value of negative PET scans after first line therapy. In conclusion, although our data confirm the prognostic value of end of treatment FDG-PET scan in T-cell lymphoma, they also highlight the limits of current prognostic stratification tools suggesting that different timing of response evaluation or alternative methods to detect minimal residual disease in those patients in CR after first line therapy are warranted. DisclosuresNo relevant conflicts of interest to declare.

Degeneration at E2 of certain spectral sequences

We propose a Hodge theory for the spaces [Formula: see text] featuring at the second step either in the Frölicher spectral sequence of an arbitrary compact complex manifold [Formula: see text] or in the spectral sequence associated with a pair [Formula: see text] of complementary regular holomorphic foliations on such a manifold. The main idea is to introduce a Laplace-type operator associated with a given Hermitian metric on [Formula: see text] whose kernel in every bidegree [Formula: see text] is isomorphic to [Formula: see text] in either of the two situations discussed. The surprising aspect is that this operator is not a differential operator since it involves a harmonic projection, although it depends on certain differential operators. We then use this Hodge isomorphism for [Formula: see text] to give sufficient conditions for the degeneration at [Formula: see text] of the spectral sequence considered in each of the two cases in terms of the existence of certain metrics on [Formula: see text]. For example, in the Frölicher case, we prove degeneration at [Formula: see text] if there exists an SKT metric [Formula: see text] (i.e. such that [Formula: see text]) whose torsion is small compared to the spectral gap of the elliptic operator [Formula: see text] defined by [Formula: see text]. In the foliated case, we obtain degeneration at [Formula: see text] under a hypothesis involving the Laplacians [Formula: see text] and [Formula: see text] associated with the splitting [Formula: see text] induced by the foliated structure.

The S.V.D. of the Poisson Kernel

The solution of the Dirichlet problem for the Laplacian on bounded regions \(\Omega \) in \({\mathbb R}^{N}, \ N \ge 2\) is generally described via a boundary integral operator with the Poisson kernel. Under mild regularity conditions on the boundary, this operator is a compact linear transformation of \(L^2 (\partial \Omega ,d \sigma )\) to \(L^2_H(\Omega )\)—the Bergman space of \(L^2\)-harmonic functions on \(\Omega \). This paper describes the singular value decomposition of this operator and related results. The singular functions and singular values are constructed using Steklov eigenvalues and eigenfunctions of the biharmonic operator on \(\Omega \). These allow a spectral representation of the Bergman harmonic projection and the identification of an orthonormal basis of the real harmonic Bergman space \(L^2_H(\Omega )\). A reproducing kernel for \(L^2_H(\Omega )\) and an orthonormal basis of the space \(L^2 (\partial \Omega ,d \sigma )\) also are found. This enables the description of optimal finite rank approximations of the Poisson kernel with error estimates. Explicit spectral formulae for the normal derivatives of eigenfunctions for the Dirichlet Laplacian on \(\partial \Omega \) are obtained and used to identify a constant in an inequality of Hassell and Tao.

FDG PET/CT response in diffuse large B-cell lymphoma: Reader variability and association with clinical outcome.

F-18-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is essential for monitoring response to treatment in patients with diffuse large B-cell lymphoma (DLBCL) and qualitative interpretation is commonly applied in clinical practice. We aimed to evaluate the interobserver agreements of qualitative PET/CT response in patients with DLBCL and the predictive value of PET/CT results for clinical outcome.PET/CT images were obtained for patients with DLBCL 3 times: at baseline, after 3 cycles of first-line chemotherapy (interim), and after completion of chemotherapy. Two nuclear medicine physicians (with 3 and 8 years of experience with PET/CT) retrospectively assessed response to chemotherapy blinded to the clinical outcome using International Harmonization Project (IHP) criteria and Deauville 5-point score. The associations between PET/CT results and progression-free survival (PFS) and overall survival (OS) were assessed using Cox regression analysis.A total of 112 PET/CT images were included from 59 patients with DLBCL (36 male, 23 female; mean age 53 ± 14 years). Using the IHP criteria, interobserver agreement was substantial (Cohen κ = 0.76) with absolute agreement consistency of 89%. Using the Deauville score, interobserver agreement was moderate (Cohen weighted κ = 0.54) and absolute consistency was 62%. The most common cause of disagreements was discordant interpretation of residual tumor uptake. With median follow-up period of 60 months, estimated 5-year PFS and OS were 81% and 92%, respectively. Neither interim nor posttreatment PET/CT results by both readers were significantly associated with PFS. Interim PET/CT result by the more experienced reader using Deauville score was a significant factor for OS (P = 0.019).Moderate-to-substantial interobserver agreement was observed for response assessments according to qualitative PET/CT criteria, and interim PET/CT result could predict OS in patients with DLBCL. Further studies are necessary to further standardize the PET/CT-based response criteria for more consistent interpretation.

Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient.

Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remains unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with revised American Fertility Society stage III/IV, rather than stage I/II. The loci are almost all located in intergenic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcription factor binding, epigenetic modification (e.g., DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis-in particular, endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonisation Project is a global standardization initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments.

Les objectifs de l’harmonisation du droit des contrats – Deux projets OHADA et les Principes OHADAC: objectifs contrastés

Abstract: The trend towards harmonization of contract law is increasingly developing, but orientations may be very different, due not only to the respective contexts, but also to the nature of objectives pursued. The present essay describes and compares three recent harmonization projects, two in the African context of the Organisation pour l’harmonisation en Afrique du droit des affaires (OHADA), the third one initiated by the Organisation pour l’harmonisation du droit des affaires dans la Caraïbe (OHADAC). The first African project, as requested by the Council of Ministers of OHADA, took strong inspiration from the UNIDROIT Principles, as the intention was to elaborate a modern instrument apt to attract investors. This project, however, has not been adopted, in particular because of a marked reluctance to depart from the French legal tradition, which is prevailing in most (but not all) member States. An alternative project, based on a private initiative, is in the process of being elaborated, with the view to remain within the dominant legal tradition and to avoid disorienting practitioners. As to the project that has just been prepared in the framework of OHADAC, it takes much inspiration from existing uniform law instruments, including the UNIDROIT Principles. At the same time, it is mainly concerned not to retain rules which could appear to be unacceptable in certain parts of a region where the legal systems are very diverse.

The Significance of Kinship for Medical Education: Reflections on the Use of a Bespoke Social Network to Support Learners' Professional Identities.

BackgroundSocial media can support and sustain communities much better than previous generations of learning technologies, where institutional barriers undermined any initiatives for embedding formal and informal learning. Some of the many types of social media have already had an impact on student learning, based on empirical evidence. One of these, social networking, has the potential to support communication in formal and informal spaces.ObjectiveIn this paper we report on the evaluation of an institutional social network—King's Social Harmonisation Project (KINSHIP)—established to foster an improved sense of community, enhance communication, and serve as a space to model digital professionalism for students at King’s College London, United Kingdom.MethodsOur evaluation focused on a study that examined students’ needs and perceptions with regard to the provision of a cross-university platform. Data were collected from students, including those in the field of health and social care, in order to recommend a practical way forward to address current needs in this area.ResultsThe findings indicate that the majority of the respondents were positive about using a social networking platform to develop their professional voice and profiles. Results suggest that timely promotion of the platform, emphasis on interface and learning design, and a clear identity are required in order to gain acceptance as the institutional social networking site.ConclusionsEmpirical findings in this study project an advantage of an institutional social network such a KINSHIP over other social networks (eg, Facebook) because access is limited to staff and students and the site is mainly being used for academic purposes.

Proposed Standards for Variable Harmonization Documentation and Referencing: A Case Study Using QuickCharmStats 1.1.

Comparative statistical analyses often require data harmonization, yet the social sciences do not have clear operationalization frameworks that guide and homogenize variable coding decisions across disciplines. When faced with a need to harmonize variables researchers often look for guidance from various international studies that employ output harmonization, such as the Comparative Survey of Election Studies, which offer recoding structures for the same variable (e.g. marital status). More problematically there are no agreed documentation standards or journal requirements for reporting variable harmonization to facilitate a transparent replication process. We propose a conceptual and data-driven digital solution that creates harmonization documentation standards for publication and scholarly citation: QuickCharmStats 1.1. It is free and open-source software that allows for the organizing, documenting and publishing of data harmonization projects. QuickCharmStats starts at the conceptual level and its workflow ends with a variable recording syntax. It is therefore flexible enough to reflect a variety of theoretical justifications for variable harmonization. Using the socio-demographic variable ‘marital status’, we demonstrate how the CharmStats workflow collates metadata while being guided by the scientific standards of transparency and replication. It encourages researchers to publish their harmonization work by providing researchers who complete the peer review process a permanent identifier. Those who contribute original data harmonization work to their discipline can now be credited through citations. Finally, we propose peer-review standards for harmonization documentation, describe a route to online publishing, and provide a referencing format to cite harmonization projects. Although CharmStats products are designed for social scientists our adherence to the scientific method ensures our products can be used by researchers across the sciences.

Working with Data in the Cross-National Survey Harmonization Project: Outline of Programming Decisions

In the Harmonization Project we use data from 22 cross-national survey projects that cover a total of 142 countries or territories over a time span of almost 50 years (1966–2013). The large volume of the data, their multilevel structure as well as the large number of source files encouraged us to develop a set of custom tools for extracting, transforming, and loading data into a common database that allows for efficient automation of repeatable and otherwise manual routines. We created an environment based on freeware and open-source software that constitutes an alternative to statistical packages typically used for such purposes in social science research. This platform allows us to store and manage data in a single place, and—what is crucial—enables us to easily manipulate data in order to prepare the harmonized data set for use in substantive analyses. This article presents our motivation for choosing a custom programming and database environment, describes the principles guiding our software choices, and outlines the stages of data processing.

The convergence of contract law in Europe and the problem of legitimacy: a common lawyer’s perspective

In 2001, the European Commission mooted the idea that contract law should converge in Europe. The idea generated wide-ranging debate about the merits of convergence. The multi-disciplinary nature of this debate has led to important insights, but also conceptual confusion. In this paper, I rely on philosophical tools to clarify key concepts, and identify central issues. In particular, I argue that value pluralism and state sovereignty give rise to the central problem of the legitimacy of the harmonisation project. The issue of legitimacy has not been handled well in the literature. There has been an overly narrow focus on the issue of constitutional legitimacy, or the notion of ‘legitimacy as consent’. I attempt to broaden the discussion by considering other accounts of legitimacy. I argue that whichever account is used, the legitimation burden is significant and it is unclear it has been surmounted. Beyond legitimacy, I consider how efficacy considerations seem to militate against convergence.

Some Remarks on Harmonic Projection Operators on Spheres

Presentiamo un sunto di alcuni risultati recenti relativi alle proprieta degli operatori di proiezione armonica, che mappano lo spazio delle funzioni a quadrato sommabile sulla sfera unitaria complessa e quaternionica sopra gli autospazi congiunti per l'operatore di Laplace-Beltrami e per un sublaplaciano. Discutiamo, in particolare, analogie e differenze fra il caso reale, quello complesso e quello quaternionico.

Early Treatment Intensification with R-ICE Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) Using Zevalin-BEAM for Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) As Identified By Interim PET/CT Scan Performed after Four Cycles of R-CHOP-14: A Multicenter Phase II Study of the Australasian Leukaemia Lymphoma Study Group (ALLG)

Early Treatment Intensification with R-ICE Chemotherapy Followed By Autologous Stem Cell Transplantation (ASCT) Using Zevalin-BEAM for Patients with Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) As Identified By Interim PET/CT Scan Performed after Four Cycles of R-CHOP-14: A Multicenter Phase II Study of the Australasian Leukaemia Lymphoma Study Group (ALLG)

Predictive Value of Interim 18 f-FDG PET-CT Scans on Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Study

18 F-PET-CT is clinically recommended for monitoring therapeutic response in DLBCL patients. But the role of interim PET-CT remains controversial, and most of the previous researches were retrospective. We designed this study to prospectively evaluate whether interim PET-CT was a valid prognostic tool for patients with DLBCL treated with R-CHOP regimen and if yes, try to determine the more appropriate time and interpretation method for interim PET-CT.This study was a sub-study of the parental study "A prospective, multicenter randomized phase III clinical trial of intensified chemotherapy in improving the treatment efficacy of patient with diffuse large B-cell lymphoma" (NCT01793844). The sub-study included patients that have already been enrolled in the parent study at Sun Yat-Sen University Cancer Center prospectively. Patients were evaluated with PET-CT scans before treatment and after every 2 cycles of R-CHOP and after the completion of first-line treatment. Regular follow-up starts from the enrollment.Between Jan. 2008 and Aug. 2014, 221 patients in Sun Yat-Sen University Cancer Center were enrolled in this sub-study, among whom 203 patients were included in the analysis and the other 18 were excluded for lacking the necessary raw data of PET-CT scan. PET evaluation would be applying the visual criteria of International Harmonization Project(IHP) and the Deauville 5-point scale(5-PS). The results showed PET positive in 103 patients and negative in 100 patients after 2 cycles of R-CHOP chemotherapy with IHP criteria. Among the 103 patients with positive PET-2, 53 patients turned negative after 4 cycles of chemotherapy and still 50 patients remain positive. At the evaluation of end-of-first-line-treatment, 165 patients achieved CR, while 30 achieved PR and 8 PD . According to 5-PS criteria, 146 patients were PET negative with 57 were positive after 2 cycles of chemotherapy. And 173 patients were negative in PET-4 evaluation, while 30 patients remained positive. With a median follow-up of 25.46 months (range 3.60~77.33 months) and according to IHP criteria, patients with negative PET-2 had superior 3-year PFS (84.7% vs. 63.8%, p < 0.001) and OS (89.8% vs. 80.4%, p = 0.045) than those with positive results. Patients with negative PET-4 also had a better clinical outcome compared with the positive group with 3-year PFS (84.1% vs. 43.8%, p < 0.001) and OS (90.7% vs. 67.8%, p < 0.001). A further analysis showed that patients who achieved PET negative just after 2 cycles of chemotherapy (Early responder, ER) had a similar prognosis comparing with those who achieved PET negative after 4 cycles (Later responder, LR). There were no significant differences in the persistent CR rates (87.00% vs. 86.79%, p = 0.971), 3-year PFS (84.7% vs. 82.2%, p = 0.867) and 3-year OS (89.8% vs. 92.9%, p = 0.638) between the ER group and the LR group. Patients who remained PET positive after 4 cycles of chemotherapy (Interim non-responder, I-NR) had the worst prognosis. Their persistent CR rate (42.00% vs. 87.00%, p < 0.001; 42.00% vs. 86.79%, p < 0.001), 3-year PFS (43.8% vs. 84.7%, p < 0.001; 43.8% vs. 82.2%, p < 0.001) and 3-year OS (67.8% vs. 89.8%, p < 0.001; 67.8% vs. 92.9%, p = 0.002) were significantly lower, comparing with the ER and LR group. And according to 5-PS criteria, the results were similar. Patients with negative PET-2 had superior 3-year PFS (82.9% vs. 51.6%, p < 0.001) and OS (89.7% vs. 72.9%, p = 0.001) than those with positive results. Patients with negative PET-4 also had a better clinical outcome compared with the positive group with 3-year PFS (81.8% vs. 30.0%, p < 0.001) and OS (90.1% vs. 54.2%, p < 0.001). In the multivariate analysis, PET-4 with IHP criteria, PET-4 with 5-PS criteria and IPI score were independent predictive factors for PFS of patients with DLBCL. A further analysis of positive predictive value (NPV) and negative predictive value (PPV) showed PET-4 was superior than PET-2, especially interpretated with 5-PS. The PPV and NPV of PET-4 with 5-PS criteria were 70.00% and 83.82% respectively.These data indicates that Interim 18 F-FDG PET-CT scan could predict the prognosis of DLBCL patients treated with R-CHOP regimen. And it was recommended that interim 18 F-FDG PET-CT scan be done after 4 cycles of chemotherapy, and that 5-PS criteria be applied in the interpretation of interim PET-CT scan rather than IHP criteria. DisclosuresNo relevant conflicts of interest to declare.

PD-1 Blockade with Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Safety, Efficacy, and Biomarker Assessment

PD-1 Blockade with Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Safety, Efficacy, and Biomarker Assessment

Evaluation of Absolute Lymphocytes: Absolute Monocytes (ALC:AMC) Ratio As Prognostic Marker in Classical Hodgkin Lymphoma Patients Treated with ABVD Chemotherapy at a Single Center in Saudi Arabia

In our clinical practice, international prognostic score (IPS) comprising of seven parameters has been in use for prognostication of advance stage Hodgkin's lymphoma (HL). Simple scoring system, that can stratify patients and or predict outcome both in early stage and advance stage HL, would be both helpful and practical to apply in daily practice. This is a retrospective study to find out whether recently reported absolute monocyte count (AMC) and absolute lymphocyte : monocyte ratio (LMR) at diagnosis are valid parameters for predicting prognosis of classical Hodgkin lymphoma (cHL) patients treated with ABVD at our center. Among many cut-off values for ALC/AMC ratio reported in literature (1.1, 1.5, 2.1, 2.8, 3.5) we chose the cut off of ≥2.1 as reported in the largest series by Tadmore et al.Data from patients' records were collected after approval by local institutional review board. All studies were performed in accordance with the principles of the Declaration of Helsinki. Patients were included into this study if they had histopathological diagnosis of cHL, no human immunodeficiency virus infection, availability of data on all clinical and laboratory features and treatments given, as well as outcome, and follow-up. Only patients treated with ABVD as initial chemotherapy with or without subsequent radiation therapy were included as this chemotherapy regimen is currently considered the standard of care in North America and at our institution.Response criteria were based on the guidelines from the International Harmonization Project on Lymphoma revised by Cheson et al.We excluded 4 patients with Nodular Lymphocyte Predominant HL(NLPHL), as NLPHL is considered to be a different disease entity. Hence we found 164 patients with cHL treated at King Fahad Medical City, Riyadh from 2006, through July 2015 with ABVD. Out of 164 patients we identified nodular sclerosis 116/164 (70%) and mixed cellularity 31/164 (19%) were the most common. The median age of the patients was 26 years (range, 14-86 years); 70 (41.6%) patients had bulky disease, 84 (52.1%) had extranodal disease; Median IPS was 3; Pre-Treatment ALC median was 1635/ul (range 192-825), AMC median was 841/ul (range 60-9600), and Pre-Treatment ALC/AMC Ratio (LMR) median was 2.168 (range 0.28-19.81). Overall survival was for ALC/AMC Ratio of >=2.1 was 97.5% and 92.8% for ALC/AMC Ratio of <2.1 (p=0.172) indicating some trend for better outcome.This study confirms that L/M ratio has prognostic value in cHL. However we plan to define our own best cut off value by ROC and AUC analysis as ALC/AMC Ratio of ≥2.1 did not discriminate survival advantage clearly in our patients. In addition to geographical and genetic differences, variations in hematology cell counters may be a plausible contributing factor. TableVariablesNumber(%)Age(yr)<=45140(85.4)> 4524(14.6)GenderMale88(53.7)Female76(46.3)Stage of diseaseEarly15(9.1)Advanced149(90.9)BulkyNo94(57.3)Yes70(42.7)Stage IVNo92(56.1)Yes72(43.9)HistopathologyLymphocyte Rich6(3.7)Classical11(6.7)Mixed Cellularity31(18.9)Nodular Sclerosis116(70.7)ExtranodalNo80(48.8)Yes84(51.2)Albumin<40134(85.4)>=4023(14.6)Hemoglobin<10.559(36.0)>=10.5105(64.0)WBC<15127(77.4)>=1537(22.6)IPS Score05(3.0)134(20.7)242(25.6)342(25.6)432(19.5)57(4.3)62(1.2)ALC<60016(10.3)>=600140(89.7)ALC<0.622(14.1)>=0.6134(85.9)AMC<75070(44.9)>=75086(55.1)ALC/AMC Ratio<2.172(46.2)>=2.184(53.8) DisclosuresNo relevant conflicts of interest to declare.

The Role of Interim F-18 FDG PET/CT in Patients of T Lymphoblastic Leukemia/Lymphoma Treated with ALL-Type Regimens

Background:T lymphoblastic leukemia/lymphoma (T-LBL) is highly aggressive. Although intensive chemotherapies such as acute lymphoblastic leukemia (ALL)-type regimens are commonly used, about half adult patients eventually relapse and die of T-LBL. Overwhelming evidences have confirmed the role of interim F-18 FDG PET/CT in Hodgkin lymphoma and many ongoing studies have implemented risk-adapted strategy determined by interim FDG-PET/CT. However, the role of interim FDG-PET/CT in T-LBL remains unclear.Materials and methods:47 adult patients of T-LBL treated with ALL-like regimens were retrospectively reviewed. They were treated with modified Berlin-Frankfurt-Münster (BFM)-90 regimen (n=27), Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 regimen (n=5), hyperCVAD/MA regimen (n=12), or other unspecified regimens (n=3). Interim (defined as the period between induction therapy and re-induction therapy) FDG-PET/CT was done in all 47 patients and evaluated according to the International Harmonization Project (IHP) criteria.Results:The male to female ratio was 3:1, and 29.8% of patients were older than 30 years old. About 90% of patients had mediastinal mass at presentation and 53.2% had bone marrow infiltration. 85.1% of patients had advanced disease. After induction therapy, interim FDG-PET/CT was positive in 19 patients (40.4%), most of whom had residual disease in the mediastinal lesion. Subsequent treatments were not changed according to this interim PET/CT results. After a median follow up time of 28 months, the 2-year and 3-year progression free survival (PFS) rate were 39% and 30%, respectively, and the 2-year and 3-year overall survival (OS) rate were 54% and 45%, respectively. Using Kaplan-Meier survival analysis and log-rank test, it was found that interim FDG-PET/CT positivity correlated with significantly inferior PFS and OS (p=0.002 and 0.010, respectively). Furthermore, patients with higher age (>30) had inferior PFS and OS than younger patients (p=0.037 and 0.036, respectively). However, there were no significant relationship between PFS, OS and bone marrow infiltration, LDH level, and stages (p>0.05).Conclusions:Interim FDG-PET/CT may predict PFS and OS in adult patients of T-LBL treated with ALL-type regimens, which needs to be validated in prospective clinical trials. The optimal criteria for interim FDG-PET/CT evaluation and risk-adapted treatment strategy determined by interim FDG-PET/CT should be investigated in future clinical practice. DisclosuresNo relevant conflicts of interest to declare.

Prognostic values of interim and post-therapy 18F-FDG PET/CT scanning in adult patients with Burkitt's lymphoma.

BackgroundThe prognostic values of interim and post-therapy fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) scanning have been confirmed in several subtypes of lymphoma. However, its prognostic value in Burkitt’s lymphoma has not been clearly defined. The aim of the present study was to assess the prognostic value of PET/CT scanning during different treatment processes of Burkitt’s lymphoma.MethodsA total of 29 adult patients with newly diagnosed Burkitt’s lymphoma were retrospectively involved in this study; of them, 23 patients underwent baseline PET/CT, 15 patients underwent mid-therapy PET/CT after 1–4 cycles of chemotherapy, and 17 patients underwent post-therapy PET/CT after all planned first-line chemotherapy cycles. Mid-therapy and post-therapy PET/CT results (positive vs. negative) were visually interpreted according to the criteria of the International Harmonization Project. The reduction in the maximum standardizes uptake values (∆SUVmax) of 25%, 50%, and 75% were regarded as cutoff points. Overall survival (OS) and progression-free survival (PFS) were regarded as the major endpoints.ResultsThe median OS and PFS were 27.6 months (range 6.5–78.3 months) and 27.2 months (range 3.0–78.3 months), respectively. The median SUVmax of the baseline PET/CT was 18.3 (range 1.6–35.9), whereas the median SUVmax of the mid-therapy and post-therapy PET/CT decreased to 4.0 (range 0–17.6) and 3.0 (range 0–14.5), respectively. The patients’ Eastern Cooperative Oncology Group (ECOG) scores (<2 vs. ≥2) were significantly associated with the baseline PET/CT SUVmax. The mid-therapy and post-therapy PET/CT results (positive vs. negative) showed no significant association with OS or PFS. The optimal cutoff ∆SUVmax from the baseline to the post-therapy PET/CT that could predict a change in OS in patients with Burkitt’s lymphoma was 50% (P = 0.019).Conclusions18F-FDG uptake was intense in Burkitt’s lymphoma, and there was a significant reduction in SUVmax during the interim and post-therapy PET/CT procedures. A ∆SUVmax of greater than 50% was a favorable cutoff point to predict the OS of Burkitt’s lymphoma patients.

CIP-UQIM: A unified model for quality improvement in software SME's based on CMMI level 2 and 3

ContextSoftware Process Improvement (SPI) is among the most effective ways to improve the quality of software products and services. Despite many research and industrial reports, SPI planning and implementation in Multi-Model Environments (MMEs) still face various issues and difficulties which increase the risk of failure especially for Small and Medium size Enterprises (SMEs). As a popular approach, harmonization techniques are used to meet the MME's specific issues through recognizing the common or similar areas among the implemented models and developing an integrated solution for quality improvement throughout the organization. ObjectiveThis paper has two main objectives: (1) recognizing the set of most popular models used in worldwide harmonization projects and implemented or requested by Iranian software SMEs. (2) Comparing and integrating these models in Process Activity level to develop a unified quality improvement model. MethodA combination of literature review and questionnaire methods was used to identify the set of the most popular models. Then, based on harmonization techniques the common or similar areas among these models are recognized and then an initial version of the Unified Quality Improvement Model (UQIM) is developed, named CIP-UQIM. Next, this initial model was presented in a two-day workshop for SPI experts and it was refined and finalized by incorporating their feedbacks. ResultsInvestigations showed that the set {CMMI-DEV, ISO 9001, and PMBOK} was the most popular. Thus in CIP-UQIM, for the first time, the last version of these models was unified at the activity level details. Finally, the experience of using CIP-UQIM in an Iranian SME has been reported which demonstrate its applicability and advantages. ConclusionConsidering the high similarity among the three models and CIP-UQIM level of details, it can be concluded that CIP-UQIM can be beneficial to resolve or reduce SPI issues in MME's, especially in case of software SMEs.

Simplified neutrosophic harmonic averaging projection-based method for multiple attribute decision-making problems

A simplified neutrosophic set is a subclass of a neutrosophic set and includes the concepts of a single valued neutrosophic set and an interval neutrosophic set, which can be used in real science and engineering applications with the incomplete, indeterminate and inconsistent information which exists commonly in real situations. Then, projection measure is a very suitable tool for dealing with multiple attribute decision-making problems because it can consider not only the distance but also the included angle between objects evaluated. Therefore, the main purpose of the paper is to present a simplified neutrosophic harmonic averaging projection measure and its multiple attribute decision making method with simplified neutrosophic information. Through the harmonic averaging projection measure between each alternative and the ideal alternative, the ranking order of all alternatives can be determined and the best alternative can be easily obtained as well. Finally, an illustrative example demonstrates the application and effectiveness of the proposed projection measure method in a simplified neutrosophic multiple attribute decision-making environment.