12 research outputs found
Structural, elastic, electronic and magnetic properties of quaternary Heusler alloy Cu2MnSi1-xAlx (x = 0 - 1): First-principles study
No full textWe investigate the structural, elastic, electronic and magnetic properties of the Heusler compounds Cu2MnSi, Cu2MnAl and Cu2MnSi1-xAlx quaternary alloys, using the full-potential linear-augmented plane-wave method (FP-LAPW) in the framework of the density functional theory (DFT) using the generalized gradient approximation of Perdew-Burke-Ernzerhof (GGA-PBE). Our results provide predictions for the quaternary alloy Cu2MnSi1-xAlx (x = 0.125, 0.25, 0.375, 0.5) in which no experimental or theoretical data are currently available. We calculate the ground state’s properties of Cu2MnSi1-xAlx alloys for both nonmagnetic and ferromagnetic configurations, which lead to ferromagnetic and metallic compounds. Also, the calculations of the elastic constants and the elastic moduli parameters show that these quaternary Heusler alloys are ductile and anisotropic.</jats:p
Exploring the electronic structure, mechanical stability, thermodynamic and magnetic properties of rare-earth full-Heusler alloys Pd
No full textWe have extensively studied the structural, elastic, mechanical, thermodynamic, electronic, and magnetic properties of Pd-based rare-earth full-Heusler alloys Pd2YIn (Y = Gd, La) and their quaternary alloys Pd2GdxLa1−xIn (x = 0.75, 0.5, and 0.25) using the full-potential linearized augmented-plane wave (FP-LAPW) approach in the generalized gradient (GGA) approximation based on the WIEN2k program. Our findings offer a theoretical investigation of the combined Heusler alloys Pd2GdxLa1−xIn, in which most of their properties studied here have not yet been determined. It is demonstrated that the estimated equilibrium lattice constants and spin magnetic moments and the experimental values of the parent alloys agree well. The electronic structure shows that our compounds have a metallic ferromagnetic nature, except for the Pd2LaIn alloy, which is not ferromagnetic. Furthermore, the mechanical results indicate that the studied compounds are mechanically stable, anisotropic, and exhibit ductile behavior. Consequently, it is anticipated that Pd2GdxLa1−x In Heusler alloy will be interesting candidates in spintronic devices and transport applications
Enhanced Turbulence in the Taylor-Couette Flow System
No full textAbstractThe Taylor-Couette system keeps making subject to countless studies. It is used in catalytic reactors, electrochemistry, photochemistry, biochemistry and polymerization, as well as in mass transfer operations (extraction, tangential filtration, crystallization and dialysis). This work deals with a numerical study dedicated to a Taylor-Couette flow considering the influence of a pulsatile dynamic superimposed to the rotative inner cylinder. Simulations are implemented on the FLUENT commercial package where a three-dimensional and incompressible flow is considered. It is shown that the suggested controlling technique fundamentally alters the physical flow behavior resulting in substantial turbulence enhancement to which transition is instilled at a Taylor number of Ta = 17 instead of Ta = 41.33 corresponding to the non-controlled case
Energy Efficiency in Security of 5G-Based IoT: An End-to-End Adaptive Approach
No full textThe challenging problem of energy efficiency in security of the Internet of Things (IoT) is tackled in this article. The authors consider the upcoming generation of mobile networks, 5G, as a communication architecture for the IoT. The concept of adaptive security is adopted, which is based on adjusting the security level as per the changing context. It has the potential of reducing energy consumption by adapting security rather than always considering the worst case, which is energy consuming. The consideration of 5G introduces new dynamics that can be exploited to perform more adaptation. The proposed solution introduces an intelligence in the application of security, from the establishment phase to the use phase (end-to-end). The security level related to the used cryptographic algorithm/key is adapted for each node during the establishment phase, so to match with the duration of the provided services. A new strategy is formulated that considers both IoT and 5G characteristics. In addition, a solution based on the framework of the coalitional game is proposed in order to associate the deployed objects with the optimized security levels. Moreover, the application of security is also adapted during the use phase according to the threat level. Trust management is used to evaluate the threat level among the network nodes, while existing works focus on performing the adaptation during the use phase. The proposed approach achieves more adaptation through the consideration of both IoT and 5G dynamics. The analysis and performance evaluations are conducted to show the effectiveness of the proposed end-to-end approach.Peer reviewe
ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): Final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial
No full textBackground: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. Patients and methods: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. Results: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P=0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). Conclusion: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved
Development of a fluidic sensor for the detection of herbicides using thylakoid preparations immobilised on magnetic beads to aid regenerability
Get PDFFollowing the industrial revolution and advances in chemical science, the
pollution of the environment with trace organic pollutants has been steadily
increasing, which is of concern, due to their effect on the environmental and
human health. Tighter legislation that has been introduced in order to minimise
the release of harmful pollutants has led to the initiation of monitoring
programmes. For example, drinking water suppliers are obliged to
systematically monitor drinking water supplied for human consumption for a
large range of pollutants. The same applies for waste water treatment facilities.
The well-established standard methods of environmental waters analysis
require sampling and transportation of samples to the laboratory for detailed
measurements. Therefore, the timescale from sampling to reporting is not ideal,
as a considerable lag occurs.
There is therefore the potential for the use of in situ methods that overcome this
issue. As these do not currently exist, a need to address this is identified.
Biosensors are sensing devices that rely on a biologically-derived component
as an integral part of their detection mechanism. Biosensors that respond to
pollutants could be used for rapid, low cost, field-based pre-screening of water
samples.
Herbicides are considered to be the most important class of pesticides used in
the E.U. Herbicides can be highly toxic for human and animal health, and
increase in the application of herbicides in agriculture during recent decades
has resulted in immense pollution of both soil and water. About half of the
herbicides used at present in agriculture inhibit the light reactions in
photosynthesis, mostly by targeting the Photosystem II (PSII) complex.
A method of detecting certain classes of herbicides is therefore proposed; the
photosynthesis-inhibiting herbicides act by binding to PS II, a chlorophyll–
protein complex which plays a vital role in photosynthesis, located in the
thylakoid membrane of algae, cyanobacteria and higher plants. The inhibition of
PS II causes a reduced photoinduced production of hydrogen peroxide, which
can be measured by the HRP-mediated luminol chemiluminescence reaction.
The design and development of a fluidic sensor unit for the detection of such
herbicides, based upon their inhibition of the hydrogen peroxide production, will
employ the use of superparamagnetic beads in order to address issues of reuse
and regenerability.
The illumination-dependent production of hydrogen peroxide by isolated
thylakoids, and its inhibition by herbicides in a concentration-dependent
manner, were achieved and measured with the HRP-mediated
chemiluminescence reaction with luminol in a cuvette, batch format, allowing for
the detection of herbicides down to 6.0 x 10-09.The integration of the above reactions has been achieved by designing and
constructing a fluidic unit that combines the herbicide-dependent production and
the detection of hydrogen peroxide in a single fluidic assay by combining all the
individual steps in a compact, portable format, with both HRP and thylakoids
covalently coupled on superparamagnetic beads. This addresses issues of
regenerability, as the beads are introduced, used and discarded following a
measurement, controlled only by magnetic and flow forces. Herbicide detection
was achieved to a lower LOD of 5.5 x 10-10 M. The concept development,
design and construction of the fluidic unit, as well as results of the detection of
herbicides with the batch assay method has been published, in a paper by the
author (Talanta, 2008, vol. 77, no. 1, pp. 42-47),
Considerable progress has therefore been made towards developing a system
that would be suitable for automated, field deployment applications for the
detection of the most frequently used classes of herbicides; the lower LOD
however is not within the stringent legislated maximum permissible limits set for
herbicides measured in water, in European waters.
An immediate step forward would be to achieve the required lower LOD, with
the unit's development into a prototype instrument that can be field deployed
being the further goal
Prednisone dosing in diffuse large B-Cell lymphoma treatment: a systematic review and meta-analysis
No full textBackground: Chemoimmunotherapy using rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone (R-CHOP) has been the standard of care treatment of DLBCL for over 20 years. Despite its widespread usage, there is no accepted standard for the dose of prednisone in this setting which varies from fixed dose (100mg daily for 5 days) to different levels of BSA-adjusted dosage (ranging from 40-100 mg/m2 daily for 5 days). BSA-adjusted dosage results in high doses of prednisone administered to patients with increased body surface area which may lead to significant adverse events. We performed a systematic review and meta-analysis to determine if fixeddose prednisone during R CHOP therapy results in equivalent outcomes compared to BSA adjusted dosing. Methods: A comprehensive search of several databases from each database's inception to April 29th, 2024, English language, was conducted. The databases included Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The search strategy was designed and conducted by an experienced librarian with input from the study's principal investigator. Controlled vocabulary supplemented with keywords was used to search for prospective clinical studies of R-CHOP for adult patients with untreated DLBCL. Search results were reviewed independently by 2 members of the study team for final inclusion. Discrepancies were adjudicated by a third member and reviewed by the senior author. Prednisone dosage and clinical outcomes were abstracted from the available public data. Meta-analysis was performed using the metafor package in R version 4.2.2 by applying a mixed effects model to combine results from the multiple studies. The analysis was first conducted overall to determine the general effect, and then stratified by prednisone dose (fixed- vs. BSAadjusted) to explore dose-dependent variations in outcomes. Results: Our search resulted in 2287 entries which were individually reviewed by the study team. A total of 30 studies with a combined sample size of 3573 treated patients fulfilled the inclusion criteria and were included in the final analysis set. Nineteen (63%) studies with a combined sample size of 1930 patients (median 155, range 12-399) used fixed-dose prednisone. Eleven (37%) studies with a combined sample size of 1643 patients (median 70, range 9-439) used BSA-adjusted dosing. Overall survival at 2 years for all studies was 84% (SD 78%-91%) and did not differ between fixed-dose (88%, SD 79%-97%) and BSA-adjusted dose (82%, 73%-91%). Progression-free survival at 2 years for all studies was 77% (SD 68%-85%) and did not differ between fixed-dose (80%, SD 68%-93%) and BSA-adjusted dose (74%, SD 62%-86%). Complete response rate for all studies was 70% (SD 61%-80%) and did not differ between fixed-dose (67%, SD 54%-81%) and BSA-adjusted dose (77%, SD 64%-89%). Conclusion: The result of our systematic review and meta-analysis combining 30 prospective studies and a total of 3573 patients with newly diagnosed DLBCL treated with frontline R-CHOP found no difference in clinical outcomes between patients treated with fixed-dose and BSA-adjusted dose prednisone. Our findings provide scientific evidence for the widespread practice of capping prednisone at the maximum dose of 100 mg daily for 5 days, potentially avoiding unnecessary adverse effects from BSA-adjusted dosing.Introdução: A imunoquimioterapia utilizando rituximabe, ciclofosfamida, cloridrato de doxorrubicina (hidroxidaunomicina), sulfato de vincristina (Oncovin) e prednisona (R-CHOP) tem sido o tratamento padrão para o linfoma difuso de grandes células B (LDGCB) há mais de 20 anos. Apesar de seu uso disseminado, não há um padrão aceito na dose de prednisona nesse cenário. Há duas estratégias, a primeira com dose fixa (100mg diários por cinco dias) e a segunda com a dose ajustada pela área de superfície corpórea (ASC), que varia de 40-100mg/m² diários por cinco dias. Essa segunda estratégia resulta em altas doses de prednisona administradas a pacientes com área de superfície corporal aumentada, o que pode levar a eventos adversos significativos. Foi feita uma revisão sistemática e metanálise para determinar se a prednisona em dose fixa durante o tratamento com R-CHOP resultaria em desfechos equivalentes em comparação com a dose ajustada pela ASC.
Métodos: Uma busca abrangente em várias bases de dados, na língua inglesa foi feita em junho de 2022 e atualizada em abril de 2024. As bases de dados incluiram: Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews e Scopus. A estratégia de busca foi elaborada pelo investigador principal do estudo e conduzida por um bibliotecário experiente. Palavras-chaves foram usadas para buscar estudos clínicos prospectivos de pacientes adultos com diagnóstico de Linfoma Difuso de Grandes Células B e que nunca foram tratados com R-CHOP. Os resultados da busca foram revisados por dois membros da equipe, de forma independente para seleção e inclusão final. Discrepâncias foram resolvidas por um terceiro membro e revisadas pelo autor sênior. A dose de prednisona e os desfechos clínicos foram extraídos dos dados públicos disponíveis. A metanálise foi realizada usando o pacote metafor versão R 4.2.2, aplicando um modelo de efeitos mistos para combinar os resultados dos múltiplos estudos. A análise foi conduzida primeira de forma ampla para determinar o efeito geral e, em seguida, estratificada por dose de prednisona (fixa versus ajustada pela ASC) para explorar variações dependentes da dose nos desfechos.
Resultados: Um total de 2287 artigos foi revisado individualmente pelos pesquisadores, e selecionados 30 estudos, com um tamanho amostral combinado de 3573 pacientes tratados, que atenderam aos critérios de inclusão para análise final. Dezenove (63%) estudos, com um tamanho amostral combinado de 1930 pacientes (mediana de 155, intervalo de 12-399), usaram prednisona em dose fixa. Onze (37%) estudos, com um tamanho amostral combinado de 1643 pacientes (mediana de 70, intervalo de 9-439), usaram a dose ajustada pela ASC.
A sobrevida global (SG) em 2 anos para todos os estudos foi de 84% (DP 78%-91%) e não houve diferença entre a dose fixa (88%, DP 79%-97%) e a dose ajustada pela ASC (82%, 73%-91%). A progressão livre de doença (PLD) em dois anos para todos os estudos foi de 77% (DP 68%-85%) e não houve diferença entre a dose fixa (80%, DP 68%-93%) e a dose ajustada pela ASC (74%, DP 62%-86%). A taxa de resposta completa (TRC) para todos os estudos foi de 70% (DP 61%-80%) e não houve diferença entre a dose fixa (67%, DP 54%-81%) e a dose ajustada pela ASC (77%, DP 64%-89%).
Conclusão: O resultado desta sistemática e metanálise, combinando 30 estudos prospectivos e um total de 3573 pacientes diagnosticados com LDGCB tratados com R-CHOP em primeira linha, não encontrou diferença nos desfechos clínicos entre pacientes tratados com prednisona em dose fixa e dose ajustada pela ASC. Essa revisão sistemática e metanálise fornecem evidências científicas para a prática disseminada de limitar a prednisona à dose máxima de 100mg diários por cinco dias, potencialmente evitando efeitos adversos desnecessários da dose ajustada pela ASC
Low-dose Gemtuzumab-Ozogamicin as post-consolidation therapy in elderly patients with acute myeloid leukaemia: a pilot study.
Get PDFThe incidence of acute myeloid leukemia (AML) increases with
advancing age, and in older patients the chance of cure has not
substantially improved recently. In the elderly the incidence of
secondary AML is high, and is often associated with both high-
risk cytogenetic abnormalities and expression of the multidrug
resistance protein (MDR1) and p-glycoprotein (p-gp), both of
which are associated with poor outcomes (Appelbaum et al,
2006).
Gemtuzumab-Ozogamicin (GO) is a humanized anti-CD33
monoclonal antibody conjugated to Calicheamicin that is
rapidly internalized after binding to CD33. GO seems to be
more selective than conventional chemotherapy, as CD33 is
expressed on AML cells but not in normal haematopoietic
stem cells (SCs) or in non-haematopoietic tissues (Sievers et al,
2001). In a series of phase II studies including 142 patients
with AML in first relapse, GO monotherapy was associated
with a 30% overall complete remission (CR) rate, including a
26% rate in patients over 60 years of age (Sievers et al, 2001;
Larson et al, 2002). These results led to US Food and Drug
Administration approval of GO for the treatment of patients
over 60 years with relapsed AML (Bross et al, 2001). As a
consequence of these results, there is interest in extending the
use of GO to a frontline treatment for AML in combination
with conventional chemotherapy.
Little is known about the usefulness of GO as consolidation
and/or maintenance therapy, and no data on the topic have
been published to date. In particular, there are no data
concerning the safety and efficacy of GO in the setting of
post-consolidation therapy in AML patients except for a short
report concerning the effects after autologous stem cell
transplantation (ASCT) (Cascavilla et al, 2008). GO mono-
therapy has typically been administered as a 2-h infusion at a
dose of 9 mg/m2 on days 1 and 15 of treatment, but the
administration of fractionated doses has recently been reported
to have a better safety profile (Taksin et al, 2007).
We evaluated the efficacy of low-dose GO as late
consolidation therapy after CR in a subset of fit elderly
patients who were enrolled in a prospective study. From June
1999 to December 2007, 125 patients of 60 years of age or
older with morphologically-confirmed AML and non-acute
promyelocytic leukaemia were observed in our institution. The
preliminary results from 42 patients were reported in 2007
(Olivieri et al, 2007). Fit patients, selected according to
previously published inclusion criteria (Olivieri et al, 2007),
were treated with intensive chemotherapy, followed by SC
mobilization and ASCT (Olivieri et al, 2007). Patients who
successfully mobilized SCs underwent ASCT, while poor
mobilisers received a further consolidation including standard
chemotherapy or investigational immunotherapy with GO.
Among the initial 125 patients, 79 fulfilled the inclusion
criteria; of those, 56 (72Æ1%) achieved CR, and 52 received the
first intensive consolidation course followed by G-CSF to
collect SC for ASCT. In cases of mobilisation failure, patients
were allowed to chose between an experimental approach
B J H 8 1 6 8 B Dispatch: 8.3.10 Journal: BJH CE: Varun Kumar
Journal Name Manuscript No. Author Received: No. of pages: 3 PE: Subhashree
Table I. Clinical and biological characteristics of the three groups of
patients receiving consolidation with GO (A), ASCT (B), Chemo-
therapy (CHT) (C) and Allogeneic Transplantation (D).
A (%) B (%) C (%) D (%) P
Gender
Male 8 (62) 8 (42Æ1) 3 (50) 3 (60) N.S.
Female 5 (38) 11 (57Æ9) 3 (50) 2 (40)
Age (years)
Median = 70 (range, 61–76)
£70 7 (54) 10 (52Æ6) 5 (83Æ3) 4 (80) N.S.
>70 6 (46) 9 (47Æ4) 1 (16Æ7) 1 (20)
FAB subtype
M0 0 5 (26Æ5) 0 0 N.S.
M1 3 (23) 4 (21) 2 (33Æ3) 2 (40)
M2 3 (23) 8 (42) 4 (66Æ7) 2 (40)
M4 3 (23) 2 (10Æ5) 0 1 (20)
M5 3 (23) 0 0 0
M6 1 (8) 0 0 0
M7 0 0 0 0
Leucocytosis (·109/l)
WBC <10 8 (61Æ5) 9 (47Æ4) 4 (66Æ7) 4 (80) N.S.
WBC 10–50 5 (38Æ5) 6 (31Æ6) 1 (16Æ7) 1 (20)
WBC >50 0 4 (21) 1 (16Æ7) 0
Karyotype
Poor 2 (15Æ4) 7(36Æ8) 1 (16Æ7) 4 (80) N.S.
Intermediate 6 (46Æ2) 8 (42Æ1) 4 (66Æ7) 0
Favourable 2 (15Æ4) 0 1 (16Æ7) 1 (20)
NE 3 (15Æ4) 4 (21Æ1) 0 0
Secondary disease*
Yes 3 (23) 8 (42) 2 (33Æ3) 1 (20) N.S.
No 10 (77) 11 (58) 4 (66Æ7) 4 (80)
FAB, French-American-British classification; NE, not evaluated; WBC,
white blood cell.
*To chemotherapy or Myelodysplastic Syndrome.
correspondence
a 2010 Blackwell Publishing Ltd, British Journal of Haematology doi:10.1111/j.1365-2141.2010.08168.x
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including low-dose GO or a further conventional consolidation
course. GO was administered on a compassionate basis, and the
costs were charged to our department. Among the 52 patients
who received intensive consolidation, two died and seven
relapsed; thus, 43 patients were evaluable for post-remission
treatment after the SC mobilization attempt. Of those, 19
patients (44%) successfully mobilized SC and received ASCT.
Of the 24 that did not mobilise SC, 13 received GO, six patients
refused GO and received a second consolidation with chemo-
therapy, and five patients received reduced intensity
conditioning allogeneic transplant from sibling donors.
The current analysis did not include all patients receiving
allogeneic transplant because of the poor prognosis of the
disease. The disease characteristics of the remaining patients
were equally distributed in the three groups, and the data are
shown in Table I.
All the patients received GO at a dose of 3 mg/m2 three
times monthly on an outpatient basis and received common
antimicrobial prophylaxis. No patients needed hospitalisation
for infections or other major toxicities; the median duration of
neutropenia (PMN <0Æ5 · 109/l) after GO was 12 d (range
0–33 d). The main toxicities (World Health Organization
grade III–IV) were myelosuppression (n = 9), hypertransam-
inasaemia (n = 1) and anaphylaxis (n = 3); no major unex-
pected adverse events were observed. With a median follow up
of 58 months (range 19–89), a total of 15 patients were alive
and in CR: five received ASCT (median follow-up 77 months,
range 45-89), nine received GO (median follow-up 38 months,
range: 19–75 months), and one, who received chemotherapy,
has been followed for 72 months. Two patients receiving GO
relapsed and eventually died after 13 and 19 months from CR
after the first consolidation. Two more patients relapsed after
15 and 32 months after a second CR after salvage chemother-
apy, followed by three doses of GO 3 mg/m2 administered as
consolidation therapy.
In conclusion, nine of the 13 patients who received GO as
late consolidation therapy were alive and in continuous CR
(including two patients with secondary AML and two with a
complex karyotype). The Landmark survival analysis showed
better overall survival (OS) and disease-free survival (DFS)
(P = 0Æ017 and 0Æ01 respectively) in the 13 patients that
received GO (5-year OS, 60%; 5-year DFS, 67%) compared
with patients that received either ASCT (5-year OS and DFS:
26%) or chemotherapy (5-year OS and DFS: 17%) (Fig 1).
Our preliminary data support a potential role for low-dose
GO in consolidation therapy in elderly patients with AML
who are able to achieve CR after intensive induction. Late
consolidation with low-dose GO seems to be safe and easily
manageable; the myelosuppression was relevant, but generally
short. All patients received the 3 GO infusions on an
outpatient basis without further readmissions and without
fatal events.
These preliminary data encourage the use of low-dose GO as
late consolidation therapy to eliminate the minimal residual
disease (MRD) in older patients with AML. Larger studies are
needed for confirmation, possibly including monitoring of
MRD during treatment. It also remains to be established if SC
collection failure after CR represents an independent favour-
able prognostic factor in AML patients, as suggested by some
retrospective data (Keating et al, 2003).
Antonella Poloni1
Debora Capelli1
Silvia Trappolini1
Benedetta Costantini1
Mauro Montanari1
Guido Gini1
Ilaria Scortechini1
Giorgia Mancini1
Giancarlo Discepoli2
Pietro Leoni1
Attilio Olivieri3
1Dipartimento di Scienze Mediche e Chirurgiche, Sezione di Ematologia,
Universita` Politecnica delle Marche and Azienda Ospedaliera Ospedali
Riuniti, 2Laboratorio di Citogenetica e Genetica Molecolare, Clinica di
Pediatria, Ospedali Riuniti, Ancona, and 3Azienda Ospedaliera San
Carlo, Potenza, Italy.
E-mail: [email protected]
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100
0 12 24 36 48 60 72 84 96
Cumulative probability (%)
Months
OS
GO
ASCT
CHT
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40
60
80
100
0 12 24 36 48 60 72 84 96
Cumulative probability (%)
Months
DFS
Fig 1. Comparison of the outcome (OS and DFS) of patients receiving late consolidation with Gemtuzumab-Ozogamicin (GO), autologous stem cell
transplantation (ASCT) or chemotherapy (CHT) (log rank test).
Correspondence
2 a 2010 Blackwell Publishing Ltd, British Journal of Haematology
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Keywords: AML, chemotherapy,
The function and origin of the CD4+ T cell in the classical Hodgkin lymphoma microenvironment
No full textPhDClassical Hodgkin lymphoma (CHL) is a germinal centre B cell malignancy where the bulk of the tumour comprises a non-clonal immune infiltrate enriched for CD4+ T cells. The role of these cells in the pathophysiology of CHL is poorly understood. Biomarkers predictive of clinical outcome in CHL are limited. This thesis examines microenvironment biomarkers with the goal of identifying the 10-20% of patients who are not cured by conventional therapy, and also investigates the function of the CD4+ T cell in CHL.
The prognostic power of FOXP3, a marker of regulatory T cells, CD68, a macrophage marker and CD20, a B cell marker, is validated in a new patient cohort and for the first time CD68 and FOXP3 are combined in a statistically robust scoring system. The data presented challenge the assumption that the microenvironment is Th2-polarised or senescent and demonstrates relative over-expression of T-BET, a Th1 marker and under-expression of PD1, a marker of senescence/exhaustion, with little evidence for Th2 marker expression. A cytokine-enriched in vitro culture system was developed demonstrating superior proliferation and longevity of CHL-derived T cells compared to non-malignant tissue-derived controls. These cells sustain expression of markers associated with proliferation and longevity (e.g. CD27, CD28) and remain functional (express cytokines) for many weeks. A panel of CD4+ T cell-specific markers was determined capable of differentiating CHL-derived from non-malignant or non-Hodgkin lymphoma-derived CD4+ T cells, in which markers of central memory (CD62L and CCR7) and early activation (CD69) are over-represented and markers of senescence (CD57 and PD1) are under-represented. Cytokine profiles were found to resemble Th1 (expression of IL2, IFN- and TNF expression) rather than Th2 (IL4, IL13, IL21, IL10 and IL6) responses.
The data presented confirm a new prognostic biomarker signature and show a Th1 rather than Th2-dominated microenvironment enriched for cytokine-secreting functional effector CD4+ T cells and long-lived, proliferative cells resembling central memory cells rather than hypoproliferative, anergic, non-functional T cells
