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81.
82.
Carlo Aul Aristoteles Giagounidis Ulrich Germing Arnold Ganser 《Medizinische Klinik》2002,89(9):666-676
Zusammenfassung. Hintergrund: Myelodysplastische Syndrome (MDS) sind erworbene klonale Knochenmarkerkrankungen, die durch ineffektive Hämatopoese, quantitative und qualitative Veränderungen peripherer Blutzellen sowie erhöhtes Risiko des Übergangs in akute myeloische Leukämien (AML) gekennzeichnet sind. Typisches Merkmal der Krankheitsgruppe ist ihre prognostische Heterogenität, die therapeutische Entscheidungen erschwert. Die Therapieplanung wird weiter durch das meist fortgeschrittene Patientenalter und damit verbundene Probleme der Komorbidität kompliziert. Mit Ausnahme der allogenen Blutstammzelltransplantation konnte bislang für keine Therapieform eine Überlegenheit gegenüber alleinigen supportiven Maßnahmen gesichert werden. Ziel dieses Übersichtsartikels ist es, die Grundlagen der Diagnostik sowie heutigen Behandlungsmöglichkeiten der MDS darzustellen. Diagnose und Risikostratifikation: Die Verdachtsdiagnose eines MDS gründet sich meist auf Blutbildveränderungen und andere routinemäßige bestimmte Laborbefunde. Morphologische Knochenmarkuntersuchung mit gleichzeitiger zytogenetischer Analyse ist zur Diagnosesicherung und Subklassifikation des MDS nach FAB- bzw. WHO-Kriterien sowie zur prognostischen Bewertung der Patienten nach dem International Prognostic Scoring System (IPSS) erforderlich. Behandlungsstrategien: Supportive Maßnahmen sind Standardtherapie in allen Krankheitsstadien, haben aber keinen Einfluss auf den natürlichen Krankheitsverlauf des MDS. Die allogene Blutstammzelltransplantation unter Verwendung eines HLA-identischen Familienspenders ist Therapie der Wahl bei Hochrisiko-MDS und kann nach Ausschluss von Kontraindikationen bei Patienten bis zu einem Alter von 60 Jahren durchgeführt werden. Das krankheitsfreie Überlegen beträgt 6-7 Jahre nach Transplantation 29-40%. Ungünstige Prognosefaktoren für Überleben nach allogener Stammzelltransplantation sind höheres Patientenalter, fortgeschrittenes MDS, ungünstige Chromosomenbefunde und Nachweis einer Knochenmarkfibrose. Bei jüngeren Patienten (< 40 Jahre) mit Hochrisiko-MDS, die über keinen HLA-identischen Familienspender verfügen, sollte eine Fremdspendertransplantation in Betracht gezogen werden. Intensive Polychemotherapie mit bei AML gebräuchlichen Induktionsprotokollen ist bei Hochrisikopatienten < 70 Jahre indiziert und führt zu kompletten Remissionsraten von 45-79%. In Einzelfällen sind auch ohne konsolidierende Blutstammzelltransplantation lang anhaltende Vollremissionen möglich. Bei älteren Patienten mit fortgeschrittenem MDS und Kontraindikationen gegen aggressive Chemotherapie kommen eine intravenöse Therapie mit 5-Azacytidin oder Decitabine sowie niedrig dosierte perorale Dauerbehandlung mit Melphalan in Betracht, die nach präliminären Studien zu Ansprechraten von 40-63% führen. Besseres Verständnis der pathophysiologischen Grundlagen der MDS hat in den letzten Jahren die Entwicklung neuer Therapieoptionen ermöglicht. Hierzu gehören die Behandlung mit Differenzierungsinduktoren, wie hämatopoetische Wachstumsfaktoren oder Retinoide, immunmodulatorische Therapieansätze mit Antihymozytenglobulin oder Ciclosporin A, Zytokininhibition durch Verabreichung von Amifostin, Pentoxifyllin und löslichen TNF-!-Rezeptoren sowie die Angiogenesehemmung mit Thalidomid. Schlussfolgerung: Bessere Charakterisierung des natürlichen Krankheitsverlaufs sowie der pathophysiologischen Grundlagen der MDS hat zu neuen Therapieverfahren geführt, deren genauer Stellenwert in sorgfältig geplanten, randomisierten Studien ermittelt werden muss. In Deutschland werden solche Studien durch die Deutsche MDS-Studiengruppe koordiniert und durchgeführt. Abstract. Background: Myelodysplastic syndromes (MDS) are acquired hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cellular dysfunction and an increased risk of transformation into acute myeloid leukemia (AML). One of the hallmarks of MDS is their prognostic heterogeneity which complicates therapeutic decisions. Therapeutic decisions are further hampered by the advanced age of most patients and the problem of attendant comorbidities. With the exception of allogeneic stem cell transplantation, no treatment modality has been proven to be of benefit over supportive care. The purpose of this review is to summarize the diagnostic work-up as well as current approaches to the treatment of MDS. Diagnosis and Risk Stratification: The diagnosis of MDS is based on routine laboratory and peripheral blood evaluation. Bone marrow examination along with cytogenetic analyses are required for confirming und classifying MDS according to FAB or WHO proposals as well as performing a risk analysis according to the International Prognostic Scoring System (IPSS) which distinguishes four risk groups with different life expectancies and AML incidences. Therapeutic Strategies: Supportive treatment remains the mainstay of therapy, but does not alter the natural course of MDS. The only curative treatment of MDS is allogeneic stem cell transplantation which can be performed in high-risk patients up to an age of 60 years. The disease-free survival varies between 29% and 40% at 6-7 years after transplant. Unfavorable prognostic factors of survival in allogeneic stem cell transplantation are older age, advanced MDS stage, high-risk cytogenetics, high IPSS score and marrow fibrosis. For patients with high-risk MDS younger than 40 years, a matched unrelated donor transplant should be considered. AML-type chemotherapy is increasingly used in younger patients with high-risk MDS and yields complete remission rates between 45% and 79%. Despite high relapse rates, combination chemotherapy offers a chance of long-term remission for selected patients. For patients without HLA-matched allogeneic sibling donor, autologous stem cell transplantation may be used as consolidation therapy ater successful conventional induction chemotherapy. For older patients with high-risk MDS in whom aggressive chemotherapy is contraindicated, intravenous treatment with 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine) or oral treatment with low-dose melphalan are promising new treatment options which yielded overall response rates of 40-63%. Based on new insights into the pathobiology of MDS, additional treatment approaches have been developed in recent years including differentiation therapy with hematopoietic growth factors and retinoids, immunosuppressive therapy with antithymocyte globulin or cyclosporine, cytokine inhibition by amifostine, pentoxifylline or soluble TNF-! receptor as well as angiogenesis inhibition by thalidomide. Conclusion: Increased understanding of the natural course and pathophysiology of MDS has resulted in several new treatment approaches which must be further evaluated in appropriate clinical trials. In Germany, such trials are performed and coordinated by the German MDS Study Group which is part of the program "Kompetenznetzwerk Akute und Chronische Läukemien". 相似文献
83.
Ulrich Germing Corinna Strupp Gerald Meckenstock Aristoteles Giagounidis Horst Minning und Carlo Aul 《Medizinische Klinik》1999,94(9):467-472
Zusammenfassung
□ Hintergrund Diagnostik und Klassifizierung der chronischen myelomonozyt?ren Leuk?mien (CMML) sind morphologisch schwierig und werden durch
heterogene Klinik und Erkrankungsverlauf kompliziert. Angaben über die H?ufigkeit des Leuk?mieübergangs schwanken erheblich.
Die FAB-Gruppe hat die Unterscheidung zweier Subgruppen der CMML vorgeschlagen: Anhand der peripheren Leukozytenzahlen wird
eine myelodysplastische Verlaufsform (MDS-CMML, <13 000/μl) von einer myeloproliferativen Verlaufsform (MPD-CMML, >13 000/μl)
abgegrenzt. Eindeutige Prognoseparameter konnten bislang nicht etabliert werden.
□ Patienten und Methoden Anhand des umfangreichen Datenmaterials des Düsseldorfer MDS-Registers wurden in einer retrospektiven Analyse klinische, h?matologische
und morphologische Charakteristika sowie natürlicher Krankheitsverlauf und Prognosefaktoren der CMML und ihrer morphologischen
Subgruppen verglichen.
□ Ergebnisse Von insgesamt 225 Patienten mit CMML wurden 115 als MDS-CMML und 110 als MPD-CMML klassifiziert. Das mediane Erkrankungsalter
betrug 70 bzw. 73 Jahre. In beiden Gruppen war das Geschlechtsverh?ltnis zugunsten des m?nnlichen Geschlechts verschoben.
Splenomegalie (50 vs. 28%) und Hepatomegalie (45 vs. 25%) wurden h?ufiger in der Gruppe der MPD-CMML beobachtet. In der MDS-Gruppe
wurden signifikant h?here LDH-Werte gemessen. Die peripheren Blutzellwerte unterschieden sich, abgesehen von den Leukozytenzahlen,
nicht wesentlich. Der mediane medull?re Blastenanteil betrug in beiden Gruppen 8%, Dysplasiezeichen aller drei Zellreihen
konnten in beiden Gruppen in ?hnlicher Weise nachgewiesen werden. Fünf Jahre nachDiagnosestellung lebten in der MDS-Gruppe
noch 24% und in der MPD-Gruppe noch 15% der unbehandelten Patienten. Die H?ufigkeit des übergangs in eine akute myeloische
Leuk?mie war in der MDS-Gruppe h?her als in der MPD-Gruppe (29 vs. 18% nach fünf Jahren). Unabh?ngige ungünstige Prognoseparameter
der Gesamtgruppe und der MDS-Gruppe waren erh?hte LDH-Werte, erniedrigte H?moglobinwerte und m?nnliches Geschlecht. Mit Hilfe
des Düsseldorf-Score gelang die Unterscheidung von Risikogruppen innerhalb der MDS-Gruppe mit medianen überlebenszeiten von
zw?lf vs. 40 Monaten (p=0,00005). Innerhalb der Gruppe der MPD-CMML konnten keine Prognoseparameter identifiziert werden.
□ Schlu?folgerung MDS-CMML und MPD-CMML stellen klinisch unterschiedliche Enrit?ten dar, die sich allerdings prognostisch nicht wesentlich voneinander
unterscheiden. Eine Risikostratifizierung der CMML kann mit Hilfe des Düsseldorf-Score vorgenommen werden.
相似文献
84.
Anne L. Wheeler M. Mallar Chakravarty Jason P. Lerch Jon Pipitone Zafiris J. Daskalakis Tarek K. Rajji Benoit H. Mulsant Aristotle N. Voineskos 《Schizophrenia bulletin》2014,40(4):914-924
Background: Prominent regional cortical thickness reductions have been shown in schizophrenia. In contrast, little is known regarding alterations of structural coupling between regions in schizophrenia and how these alterations may be related to cognitive impairments in this disorder. Methods: T1-weighted magnetic resonance images were acquired in 54 patients with schizophrenia and 68 healthy control subjects aged 18–55 years. Cortical thickness was compared between groups using a vertex-wise approach. To assess structural coupling, seeds were selected within regions of reduced thickness, and brain-wide cortical thickness correlations were compared between groups. The relationships between identified patterns of circuit structure disruption and cognitive task performance were then explored. Results: Prominent cortical thickness reductions were found in patients compared with controls at a 5% false discovery rate in a predominantly frontal and temporal pattern. Correlations of the left dorsolateral prefrontal cortex (DLPFC) with right prefrontal regions were significantly different in patients and controls. The difference remained significant in a subset of 20 first-episode patients. Participants with stronger frontal interhemispheric thickness correlations had poorer working memory performance. Conclusions: We identified structural impairment in a left-right DLPFC circuit in patients with schizophrenia independent of illness stage or medication exposure. The relationship between left-right DLPFC thickness correlations and working memory performance implicates prefrontal interhemispheric circuit impairment as a vulnerability pathway for poor working memory performance. Our findings could guide the development of novel therapeutic interventions aimed at improving working memory performance in patients with schizophrenia.Key words: dorsolateral prefrontal cortex, MRI, cortical thickness, structural coupling 相似文献
85.
Miran Kenk Nicolaas Paul L.G. Verhoeff Aristotle N. Voineskos David Rotenberg Alan A. Wilson Jeffrey H. Meyer Sylvain Houle Romina Mizrahi 《Synapse (New York, N.Y.)》2014,68(11):536-547
The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second‐generation radioligand, [18F]‐FEPPA, and high‐resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM‐ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T1‐weighted magnetic resonance image using a diffusion tensor imaging‐based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high‐affinity binders (HAB), mixed‐affinity binders (MAB), and low‐affinity binders. [18F]‐FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two‐tissue compartment model showed moderate identifiability (coefficient of variation 15–19%) for [18F]‐FEPPA total volume distribution (VT) in WM‐ROIs. Noise affects VT variability, although its effect on bias was small (6%). In a worst‐case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [18F]‐FEPPA VT in WM‐ROIs. We found no association between age and [18F]‐FEPPA VT in WM‐ROIs. The VT values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [18F]‐FEPPA PET to measure TSPO expression in WM. Synapse 68:536–547, 2014 . © 2014 Wiley Periodicals, Inc. 相似文献
86.
The main aim of this article is to present a research agenda and systematic framework of what the field of health information systems is about, namely its central topics and connecting areas. In doing so, we try to provide a cohesive 'big picture' for academics and professionals that are interested in conducting research in this broad area. By using a large number of disparate data sources, we identified 3 major research fields and 18 sub-fields. As this discipline is quite new and heterogeneous in terms of themes and the educational backgrounds of its researchers, we see our conceptualisation as a first step in obtaining a collective understanding of this field, as well as being a common starting point for discussing future directions. 相似文献
87.
Adrian Fernando Palma Grzegorz Zuk Dimitri Aristotle Raptis Sophia Franck Gertraud Eylert Florian Samuel Frueh 《Journal of plastic surgery and hand surgery》2016,50(5):262-271
Background Recently published data show that many women interested in breast augmentation (BA) actively search the Internet for information. The Internet is currently the main source of information on this topic.Objectives Little is known about the quality of available information on the Internet concerning BA. The goal was to evaluate this in a systematic manner using a validated and reproducible tool.Methods Women (n?=?96) unrelated to medicine were asked which keywords they would use to search the Internet if they were interested in BA. Five keywords were used. Qualitative and quantitative assessment was performed with the modified Ensuring Quality Information for Patients (EQIP) tool. A total of 2500 websites containing information on BA were identified using Google, Bing, Yahoo, Ask, and AOL.Results Out of 623 eligible websites, only 153 (25%) addressed more than 20 EQIP items. Scores were higher for encyclopaedias and academic websites compared to hospital and practitioner websites. The median EQIP score was only 15 (IQR = 12–20), and quantitative postoperative morbidity and mortality risk estimates were available in only 38% and 25% of the websites, respectively. Major complications (e.g. capsular contraction, implant safety) were mentioned in only 156 (25%) of the websites.Conclusions This is the first assessment of online patient information on BA using the EQIP tool. This analysis demonstrated several shortcomings in the quality of information provided to BA candidates. There is an immediate need for better informative and educational websites regarding BA procedures that are compatible with international quality standards for plastic surgery. 相似文献
88.
To better understand the detection and management of iron overload in transfusion-dependent patients with myelodysplastic
syndromes (MDS), a 15-min web- or paper-based survey was conducted among 338 European physicians from 27 countries. Respondents
had a mean of 18 years of clinical experience. Forty-six percent and 27% of physicians noted that detecting and treating iron
overload were either “very important” or “important,” respectively. The main reason for not actively exploring iron overload
was related to poor patient prognosis, while the main reasons for not initiating iron chelation therapy were poor patient
prognosis and older patient age. Thirty-seven percent and 31% of physicians believed that treating iron overload in these
patients was “very important” or “important,” respectively. Ninety percent of physicians prescribed iron chelation therapy,
and 38% of transfusion-dependent patients received iron chelation therapy. The key reasons for not initiating iron chelation
therapy were related to poor patient prognosis (72%), patient age ≥85 years (50%), and comorbidities (34%). The views of these
experienced MDS physicians reflect available international MDS treatment guidelines. 相似文献
89.
Fenaux P Giagounidis A Selleslag D Beyne-Rauzy O Mufti G Mittelman M Muus P Te Boekhorst P Sanz G Del Cañizo C Guerci-Bresler A Nilsson L Platzbecker U Lübbert M Quesnel B Cazzola M Ganser A Bowen D Schlegelberger B Aul C Knight R Francis J Fu T Hellström-Lindberg E;MDS- Lenalidomide delq Study Group 《Blood》2011,118(14):3765-3776
This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for ≥ 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P < .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression to acute myeloid leukemia (AML). Cytogenetic response rates were 50.0% (10 mg) versus 25.0% (5 mg; P = .066). For the lenalidomide groups combined, 3-year overall survival and AML risk were 56.5% and 25.1%, respectively. RBC-TI for ≥ 8 weeks was associated with 47% and 42% reductions in the relative risks of death and AML progression or death, respectively (P = .021 and .048). The safety profile was consistent with previous reports. Lenalidomide is beneficial and has an acceptable safety profile in transfusion-dependent patients with Low-/Intermediate-1-risk del5q myelodysplastic syndrome. This trial was registered at www.clinicaltrials.gov as #NCT00179621. 相似文献