Peter Martus

University of Tuebingen, Tübingen, Baden-Württemberg, Germany

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Publications (380)1461.65 Total impact

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    ABSTRACT: The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome. A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of 2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported. Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72 %, respectively. In all, 29 % (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22 %, and 60 and 52.7 %, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30 %). In addition, 15.5 % (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28 %); 12 of 110 patients (11 %) presented with symptoms from osteoporosis, 5 of 110 patients (4.5 %) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11 % reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented. Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic breadth.
    Strahlentherapie und Onkologie 03/2014; · 4.16 Impact Factor
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    ABSTRACT: Primary headache disorders should be diagnosed based on the detailed history of the patient. However, only few questions are necessary to allocate the symptoms to migraine, tension-type headache or other primary headaches in most cases. The "Rostock Headache Questionnaire" (Rokoko) is suitable for being completed by the investigator or the patient him/herself within a few minutes. Validation parameters of a sample of n = 87 patients (median: 44 years), diagnosed by headache experts in a personal interview ("gold standard"), are presented. Sensitivity and specificity for migraine without aura (0.87/0.51), migraine with aura (0.71/0.95), tension-type headache (0.57/0.93), or a combination of both (0.22/0.93) are based on the parameters pain frequency (recurrent vs. permanent), and the presence or absence of aura symptoms. To differentiate tension-type headache into episodic or chronic forms, the questionnaire can be analysed individually based on the frequency of headache days. The questionnaire enables the fast acquisition of relevant data in headache diagnosis and headache research with sufficient sensitivity and specificity. In addition, further information about triggering and symptoms of headaches can be assessed. The questionnaire can be used both by neurologists or psychiatrists and by general practitioners. The questionnaire does not replace the physical examination.
    Fortschritte der Neurologie · Psychiatrie 03/2014; 82(3):145-8. · 0.85 Impact Factor
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    ABSTRACT: Assessment of glomerular filtration rate (GFR) is crucial as the GFR value defines the stage of chronic kidney disease (CKD) and determines the adjustment of drug dosing. The aim was to investigate a new way for the accurate determination of glomerular filtration rate (GFR) in older adults based on the combination of an exogenous filtration marker, iohexol, and an endogenous marker, serum creatinine or cystatin C. We combined variables for the estimation of GFR (eGFR) with a reduced set of measurements of the marker iohexol (mGFR). In a population based sample of 570 subjects (70 ys plus) from the Berlin Initiative Study (BIS) we investigated (1) the BIS1 and BIS2 equations based on age, gender, serum creatinine, and on serum cystatin C, (2) equations based on one or two iohexol measurements, and (3) equations based on the combination of variables from BIS1 or BIS2 with iohexol measurements. Reference standard was based on eight iohexol measurements. The cut off of 60 mL/min per 1.73 m(2) was chosen to assess accuracy. Equations were constructed using a learning sample (n = 285) and an independent validation sample (n = 285). Misclassification rates were 17.2% (BIS1), 11.6% (BIS2), 14.7% (iohexol240 , iohexol measurement 240 min), 7.0% (iohexol240 combined with variables included in BIS1), and 6.7% (iohexol240 combined with variables included in BIS2). Misclassification rates did not decrease significantly after inclusion of two or three iohexol measurements. Combined strategies for the determination of GFR lead to a relevant increase of diagnostic validity.
    British Journal of Clinical Pharmacology 01/2014; · 3.58 Impact Factor
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    ABSTRACT: Background Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice.
    The Journal of allergy and clinical immunology 01/2014; · 12.05 Impact Factor
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    ABSTRACT: Experimental studies suggest that a large proportion of opioid analgesia can be mediated by peripheral opioid receptors. This trial examined the contribution of such receptors to clinical analgesia induced by intravenous morphine. We hypothesized that the selective blockade of peripheral opioid receptors by methylnaltrexone (MNX) will increase the patients’ demand for morphine to achieve satisfactory postoperative pain relief. In a double-blind, placebo-controlled, sequential two-center trial, 50 patients undergoing knee replacement surgery were randomized (1:1) to receive either subcutaneous MNX (0.9 mg/kg) (hospital I: n=14; hospital II: n=11) or saline (hospital I: n=13; hospital II: n=12) at the end of surgery. Primary endpoint was the cumulative amount of intravenous morphine administered during the first 8 hours. Secondary endpoints were pain scores at rest and during movement (by Numerical Rating Scale and McGill Questionnaire), vital signs, adverse side effects and withdrawal symptoms. After MNX, demands for morphine were strongly (by about 40%) increased (hospital I: 35.31 ± 12.99 mg vs. 25.51 ± 7.92 mg, P=0.03; hospital II: 35.42 ± 11.73 mg vs. 24.80 ± 7.84 mg, P=0.02; pooled data: P<0.001; means ± SD). Secondary endpoints were similar in all groups (P>0.05). Thus, a significant proportion of analgesia produced by systemically administered morphine is mediated by peripheral opioid receptors. Drugs that selectively activate such receptors should have the potential to produce powerful clinical pain relief.
    Pain. 01/2014;
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    ABSTRACT: Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome ("disease modifying factor"). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic' including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury.Methods/design: SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31--55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial. The objectives are to characterize the dysfunction of the innate and adaptive immune system after spinal cord injury and to explore its proposed 'neurogenic' origin by analyzing its correlation with lesion height and severity. The trial protocol considers difficulties of enrolment in an acute setting, and loss to follow up. The administrative interim analysis confirmed the feasibility of the protocol. Better understanding of the SCI-IDS is crucial to reduce co-morbidities and thereby to attenuate the impact of disease modifying factors to protect neurological "outcome at risk". This putatively results in improved spinal cord injury medical care.Trial registration: DRKS-ID: DRKS00000122 (German Clinical Trials Registry).
    BMC Neurology 11/2013; 13(1):168. · 2.56 Impact Factor
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    ABSTRACT: Background: As there are scarce data from Germany addressing home-based infusion therapy in chronically ill patients, a study on transferring infusion therapy from in-patient-treatment to home care, exemplified for Fabry's disease, was conducted. Methods: A total of 69 patients on enzyme replacement infusion therapy (ERT with agalsidase alfa every two weeks) were enrolled in the open, non-controlled, multicentre, non-interventional observational study. After uneventful ERT in a hospital setting, intravenous treatment was administered at home by a specially-trained nurse. Primary outcome measure was change in patient satisfaction measured by an eleven-item Likert scale. Results: The in-home observation period lasted between 96 und 401 days (median 180; IQR 166-184). Patient satisfaction increased significantly with home-based therapy (p = 0.001). A quality of life analysis (SF-36) demonstrated significant improvements in role-physical (p = 0.003), bodily pain (p = 0.032), vitality (p < 0.001), social functioning (p = 0.020), role-emotional (p = 0.007), mental well-being (p = 0.007) and mental sum score (p = 0.002). Home infusions turned out to be safe and were well tolerated. Conclusion: Chronically ill patients with need for regular infusion therapy may benefit from a home care setting. Home-based infusion therapy as exemplified by agalsidase alfa ERT in Fabry's disease is a viable option for patients who received uneventful infusions within the hospital.
    DMW - Deutsche Medizinische Wochenschrift 11/2013; 138(46):2345-50. · 0.65 Impact Factor
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    ABSTRACT: We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information. We analyzed the scans of 2,979 patients (aged 18-55 years) enrolled in the sifap1 project with clinical evidence of ischemic stroke (IS) or clinically defined TIA in whom MRI, including diffusion-weighted imaging, was obtained within 10 days of the CVE. Age groups were categorized as 18-34, 35-44, and 45-55 years. We compared age- and sex-specific proportions of infarct features, white matter hyperintensities, and old microbleeds. Acute infarcts were identified in 1,914 of 2,264 patients (84.5%) with IS and 101 of 715 patients (14.1%) with TIA. Among patients with IS, younger age was significantly associated with acute infarcts in the posterior circulation, while anterior circulation infarcts and acute lacunar infarcts were more frequent in older age groups. One or more old infarcts were present in 26.8% of IS and 17.1% of TIA patients. This rate remained high even after excluding patients with a prior CVE (IS, 21.7%; TIA, 9.9%). The prevailing type of old infarction was territorial in patients younger than 45 years and lacunar in those aged 45 years or older. The frequency of white matter hyperintensities (46.4%) and their severity was positively associated with age. Old microbleeds were infrequent (7.2%). Young adults show a high frequency of preexisting and clinically silent infarcts and a relative preference for acute ischemia in the posterior circulation. Findings suggesting small-vessel disease become apparent at age 45 years and older.
    Neurology 11/2013; · 8.25 Impact Factor
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    ABSTRACT: Recurrent angioedema (RecA) is a frequent clinical problem characterized by suddenly occurring cutaneous and/or mucosal swellings. Depending on their location, RecA may be painful, hindering, disfiguring, or even life-threatening. The assessment of disease activity in affected patients is important to guide treatment decisions. Currently, however, there is no standardized and validated outcome measure available to do so. To develop and validate the first specific patient-reported outcome instrument to assess disease activity in RecA patients, the Angioedema Activity Score (AAS). After a set of potential AAS items was developed, item evaluation and reduction were performed by means of impact analysis, factor analysis, regression analysis, and by checking for face validity. In addition, the items of the final AAS questionnaire were tested for their validity and reliability during a 12-week validation study. In total, data from 110 and 80 RecA patients were used during the AAS item evaluation and validation phase, respectively. The resulting AAS consisted of five items and was found to have a one-dimensional structure and excellent internal consistency. It correlated well with other measures of disease activity and quality-of-life impairment, thus demonstrating its convergent validity. In addition, the known-groups validity and test-retest reliability of the AAS were found to be good. The AAS is the first validated and reliable tool to determine disease activity in RecA patients, and it may serve as a valuable instrument in future clinical studies and routine patient care.
    Allergy 08/2013; · 5.88 Impact Factor
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    ABSTRACT: 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is safe and effective to suppress febrile seizures in children. The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents.Prospect: The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy.Trial registration: ClinicalTrials.gov identifier: NCT01370044.
    Journal of Translational Medicine 06/2013; 11(1):157. · 3.46 Impact Factor
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    ABSTRACT: To determine whether adding myocardial CT perfusion (CTP) to CT angiography (CTA) improves diagnostic performance for coronary stents. CTA of coronary stents has been limited by nondiagnostic studies caused by metallic stent material and coronary motion. CTA and CTP were performed in 91 consecutive patients with stents before quantitative coronary angiography, the reference standard for obstructive stenosis (≥50%). If a coronary stent or vessel was nondiagnostic on CTA, adenosine stress CTP in the corresponding myocardial territory was read for combined CTA/CTP. Patients had an average of 2.5±1.8 coronary stents (1 to 10), with a diameter of 3.0±0.5 mm. Significantly more patients were nondiagnostic for stent assessment by CTA (22%; mainly due to metal artifacts (75%) or motion [25%]) versus CTP (1%, P<0.001; severe angina precluded CTP in one case). The per-patient diagnostic accuracy of CTA/CTP for stents (87%; 95% confidence interval, 78-93%) was significantly higher than that of CTA alone (71%; 61-80%; P<0.001), mainly because nondiagnostic examinations were significantly reduced (P<0.001). In the analysis of any coronary artery disease, diagnostic accuracy and nondiagnostic rate were also significantly improved by the addition of CTP (P<0.001). CTA/CTP (7.9±2.8 mSv) had a significantly lower effective radiation dose than angiography (9.5±5.1 mSv; P=0.005). The area under the receiver-operating-characteristic curve for CTA/CTP (0.82; 0.69-0.95) was superior to that for CTA (0.69; 0.57-0.82; P<0.001) in identifying patients requiring stent revascularization.\ CONCLUSIONS: Combined coronary CTA and myocardial CTP improves diagnosis of CAD and in-stent restenosis in patients with stents compared with CTA alone.
    Journal of the American College of Cardiology 06/2013; · 14.09 Impact Factor
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    ABSTRACT: BACKGROUND: Mastocytosis is frequently associated with mast cell-mediated symptoms which require relieving medication. While second generation antihistamines (sgAHs) are the first line therapeutic strategy to treat mast cell mediator-related symptoms, controlled clinical trials on how they improve quality of life have not been performed. METHODS: This randomized, double-blind, placebo-controlled, cross-over trial assessed rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale (VAS) and symptom specific quality of life questionnaire (ItchyQoL). RESULTS: The mean ItchyQoL total score and VAS symptom score were significantly improved in the rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms. CONCLUSIONS: In this first comprehensive trial of a sgAH in mastocytosis, rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life.
    Allergy 06/2013; · 5.88 Impact Factor
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    ABSTRACT: Pruritus is a major symptom of numerous skin and systemic diseases and causes a substantial burden on patients' quality of life (QoL). We report here the validation of the German version (GerItchyQoL) of the first pruritus-specific QoL instrument ItchyQoL. GerItchyQoL was created from the original version following standard protocols. It was completed by 308 patients with chronic pruritus of different origin and tested for validity, reliability and responsiveness. Factor analysis of Ger-ItchyQoL revealed the 4 domains symptoms, functioning, feelings, and self-perception. Reliability was demonstrated by good internal consistency of all domains. We confirmed convergent validity by comparing the instrument with itch severity, as measured with a visual analogue scale (VAS 0-10), and with the Short-Form-12 (SF-12), a widely used generic health-related QoL instrument. Concurrent validity was shown by the ability to discriminate between patient groups of different itch severity. Changes in GerItchyQoL scores correlated with changes in itch severity (VAS), suggesting responsiveness of the German tool. This study provides preliminary evidence of validity, reliability and responsiveness of GerItchyQoL and also shows a high impact of chronic pruritus on QoL. Further translations of ItchyQoL into additional languages will enable large-scale international, multilingual trials.
    Acta Dermato-Venereologica 03/2013;
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    ABSTRACT: BACKGROUND AND PURPOSE: Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. METHODS: Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. RESULTS: Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). CONCLUSIONS: Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies.Clinical Trial Registration Information-clinicaltrial.gov identifier: NCT00414583.
    Stroke 01/2013; · 6.16 Impact Factor
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    ABSTRACT: The pathogenesis of delayed cerebral ischemia (DCI) is multifactorial and not completely elucidated. Our objective was to determine if episodes of spreading depolarization (SD) are reflected in compromised levels of extracellular glucose monitored by bedside microdialysis (MD) in aneurysmal subarachnoid hemorrhage (aSAH) patients. Patients with aSAH, prospectively included in the COSBID (CoOperative Study on Brain Injury Depolarisations) protocol (Berlin, Heidelberg), had hourly monitoring of cerebral glucose by MD and in parallel electrocorticographic (ECoG) monitoring for SD detection on day of admission until days 10-14 after aSAH. Cerebral MD probes were placed in the vascular territory at risk for DCI. Twenty-one aSAH patients (53.3 ± 9.1 years; mean ± standard deviation), classified according to the World Federation of Neurosurgical Societies (WFNS) in low (I-III, 11) and high (IV-V, 10) grades, were studied. Of these, 13 patients (62%) presented with DCI. Median glucose was 1.48 (0.00-8.79). Median occurrence of SD was 7 (0-66)/patients. High WFNS grade (WFNS grades IV-V) patients had more SDs (p = 0.027), while the overall glucose level did not differ. In high-grade SAH patients, SDs were more frequent. Individually, the occurrence of SD was not linked to local deviations (neither high nor low) from the LOWESS (locally weighted scatterplot smoothing) trend curve for extracellular glucose concentrations. Rapid-sampling MD techniques and analyses of SD clusters may elucidate more detail of the relationship between SD and brain energy metabolism.
    Acta neurochirurgica. Supplement 01/2013; 115:143-7.
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    ABSTRACT: Treatment of hypertension in hemodialysis (HD) patients is characterised by lack of evidence for both the blood pressure (BP) target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB) that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS) blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients. Clinicaltrialsregister.eu 2005-005021-60.
    PLoS ONE 01/2013; 8(11):e79322. · 3.73 Impact Factor
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    ABSTRACT: Background The prognostic value of the NIH consensus criteria for graft-versus-host disease (GVHD) is not well defined yet.Patients and methodsWe analyzed NIH-defined GVHD in 147 acute lymphoblastic leukemia (ALL) patients.ResultsThe cumulative incidence of classic acute GVHD (aGVHD), late aGVHD and chronic GVHD (cGVHD) was 63%, 12% and 41%, respectively. cGVHD was subclassified as classic versus overlap syndrome in 40% versus 60% of cases. In multivariate Cox regression analysis with GVHD as time-dependent covariate, classic aGVHD grade III/IV had a negative impact on overall survival (OS) due to higher non-relapse mortality. cGVHD of any grade was associated with superior OS, which was due to lower relapse incidence. Classic cGVHD versus overlap syndrome had no differential impact. In 44 patients without GVHD after transplant who received donor lymphocyte infusions (DLI), the cumulative incidence of classic aGVHD, late aGVHD or cGVHD was 60%, 5% and 57%. Occurrence of cGVHD after DLI was associated with improved OS due to lower relapse incidence.Conclusions The NIH consensus criteria for GVHD clearly define prognostic subgroups in patients transplanted for ALL. The improved OS in patients developing cGVHD after transplant or DLI gives clear evidence for a potent graft-versus-leukemia effect in this indication.
    Annals of Oncology 12/2012; · 7.38 Impact Factor
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    ABSTRACT: Background. The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established thus far. In a prospective multicenter phase II study we evaluated a potentially curative chemotherapy-only regimen in these patients. Design and Methods. Adult immunocompetent patients ≤65 years received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m2 i.v. day1, ifosfamide 2 g/m2 i.v. day3-5 and liposomal cytarabine 50mg intrathecally day6) and AraC/TT/DEP (cytarabine 3g/m2 i.v. day1-2, thiotepa 40 mg/m2 i.v. day2 and i.th. liposomal cytarabine 50mg intrathecally day3) followed by high-dose chemotherapy with carmustine 400 mg/m2 i.v. day -5, thiotepa 2x5mg/kg i.v. day -4 to -3 and etoposide 150 mg/m2 i.v. day -5 to -3 and autologous stem cell transplantation day0 (HD-ASCT). Results. Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24) there was a complete remission in 15 (63%), partial remission in two (8%) and progressive disease in seven (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%+/-19 for all patients and 58%+/-22 for patients completing HD-ASCT. Conclusions. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173).
    Haematologica 12/2012; · 5.94 Impact Factor
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    ABSTRACT: Infections are a common threat to patients after spinal cord injury. Furthermore, infections might propagate neuronal death, and consequently contribute to the restriction of neurological recovery. We investigated the association of infections (i.e. pneumonia and/or postoperative wound infections) with functional neurological outcome after acute severe traumatic spinal cord injury. We screened data sets of 24 762 patients enrolled in a prospective cohort study (National Spinal Cord Injury Database, Birmingham, AL, USA). Patients were assessed according to the ASIA classification. ASIA impairment scale-classified A and B patients recruited within 24 h post-trauma (n = 1436) were selected as being a major recruitment population for interventional trials. Patients with documented pneumonia and/or postoperative wound infections (n = 581) were compared with control subjects (non-documented infections, n = 855). The functional neurological outcome parameters (i) upward ASIA impairment scale conversions; (ii) gain of ASIA motor scores; and (iii) gain of motor and sensory levels were consecutively analysed over time up to 1 year after spinal cord injury. The group with pneumonia and/or postoperative wound infections revealed less ASIA impairment scale upward conversions after 1 year than the control group (ASIA impairment scale A: 17.2 versus 23.9%, P = 0.03; ASIA impairment scale B: 57.1 versus 74.7%, P = 0.009). ASIA motor score gain [median (interquartile range)] was lower in patients with infections [ASIA impairment scale A: 8 (4-12) versus 10 (5-17), P = 0.01; ASIA impairment scale B: 19.5 (8-53.5) versus 42 (20.5-64), P = 0.03)]. Analysis of acquired motor/sensory levels supported these findings. In ASIA impairment scale A patients, the gain in motor levels (21.7 versus 33.3%, P = 0.04) and sensory levels (24.4 versus 38 of 102, 37.3%, P = 0.03) was significantly lower in the group with pneumonia and/or postoperative wound infections than in the control group. Multiple regression analysis identified pneumonia and/or postoperative wound infections as independent risk factors for impaired ASIA impairment scale upward conversion (odds ratio: 1.89, 95% confidence interval: 1.36-2.63, P < 0.0005) or lower gain in ASIA motor score (regression coefficient: -8.21, 95% confidence interval: -12.29 to -4.14, P < 0.0005). Infections associated with spinal cord injury, such as pneumonia and/or postoperative wound infections, qualify as independent risk factors for poor neurological outcome after motor complete spinal cord injury. Infections constitute a clinically relevant target for protecting the limited endogenous functional regeneration capacity. Upcoming interventional trials might gain in efficacy with improved patient stratification and might benefit from complementary protection of the intrinsic recovery potential after spinal cord injury.
    Brain 10/2012; · 9.92 Impact Factor

Publication Stats

8k Citations
1,461.65 Total Impact Points

Institutions

  • 2008–2014
    • University of Tuebingen
      • Institute for Clinical Epidemiology and Applied Biometry
      Tübingen, Baden-Württemberg, Germany
  • 2012
    • University of Zurich
      • Division of Neuropsychology
      Zürich, ZH, Switzerland
  • 2011
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Istanbul Training and Research Hospital
      İstanbul, Istanbul, Turkey
  • 2004–2011
    • Charité Universitätsmedizin Berlin
      • • Department of General, Visceral and Transplantation Surgery
      • • Department of Nephrology
      • • Department of Dermatology, Venerology and Allergology
      • • Institute of Medical Biometrics and Clinical Epidemiology
      Berlin, Land Berlin, Germany
  • 2001–2008
    • Freie Universität Berlin
      • Division of Medical Informatics
      Berlín, Berlin, Germany
  • 2000–2007
    • University of Rostock
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2006
    • Deutsches Herzzentrum Berlin
      Berlín, Berlin, Germany
  • 1993–2006
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      • • Department of Ophthalmology
      • • Department of Anatomy
      Erlangen, Bavaria, Germany
  • 2001–2003
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 2002
    • Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V.
      Berlín, Berlin, Germany
  • 1996–1998
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany