Kooperativer Bibliotheksverbund

In: European Respiratory Review, European Respiratory Society (ERS), Vol. 32, No. 168 ( 2023-06-30), p. 220221-

Abstract: A substantial proportion of tuberculosis patients remain with pulmonary symptoms and reduced physical capacity despite successful treatment. We performed a systematic review to analyse the burden of post-tuberculosis lung impairment measured by lung function testing. Methods We searched the PubMed database for articles published between database inception and November 2020 and performed meta-analyses to estimate the prevalence, type and severity of lung impairment among drug-susceptible and multidrug-resistant tuberculosis survivors. Methodological quality of included studies was assessed using the Newcastle–Ottawa scale. Results 54 articles were included in this review. For subjects with former drug-susceptible tuberculosis, the combined estimated mean was 76.6% (95% CI 71.6–81.6) of predicted for forced expiratory volume in 1 s (FEV 1 ) and 81.8% (95% CI 77.4–86.2) for forced vital capacity (FVC). In former patients with multidrug-resistant tuberculosis, it was 65.9% (95% CI 57.1–74.7) for FEV 1 and 76.0% (95% CI 66.3–85.8) for FVC, respectively. The analysis of impairment types in former patients with drug-susceptible and multidrug-resistant tuberculosis showed that 22.0% versus 19.0% had obstructive, 23.0% versus 22.0% restrictive and 15.0% versus 43.0% had mixed impairment type, respectively. In the majority of studies, at least 10–15% of tuberculosis survivors had severe lung impairment. Conclusions This systematic review showed long-term abnormal spirometry results in a significant proportion of tuberculosis survivors.

Type of Medium: Online Resource

ISSN: 0905-9180 , 1600-0617

URL: Article

URL: Article

DOI: 10.1183/16000617.0221-2022

DOI: 10.1183/16000617.0221-2022.Supp1

Language: English

Publisher: European Respiratory Society (ERS)

Publication Date: 2023

detail.hit.zdb_id: 2202947-3

In: Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, Springer Science and Business Media LLC, Vol. 62, No. 6 ( 2019-6), p. 722-728

Type of Medium: Online Resource

ISSN: 1436-9990 , 1437-1588

URL: Article

DOI: 10.1007/s00103-019-02947-5

Language: German

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 1470303-8

SSG: 20,1

SSG: 8,1

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2787-2787

Abstract: Background Most randomized clinical trials (RCT) evaluating 2nd generation tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) used as comparator the 'standard' dose of 400 mg of imatinib daily (IMA 400). When major molecular remission (MMR) after 12 months of therapy is used as primary endpoint to measure short term outcome this might however not be the correct comparator. Several studies showed that treatment with a dose of 800mg of imatinib per day (IMA 800) achieves higher rates of MMR at 12 months compared to IMA 400. The objective of our work is to systematically review randomized trials comparing IMA 400 and IMA 800, to calculate a pooled estimator and to compare the result to a pooled estimator of trials evaluating a 2nd generation TKI in comparison to IMA 400. Patients and Methods We searched Medline for RCTs of IMA 400, IMA 800 and 2nd generation TKIs. We extracted data on study designs, treatments, patient numbers and characteristics, statistical analysis methods and MMR at 12 months. Relative risks and respective 95% confidence limits were calculated and pooled using a random effects model. Forest plots were printed to visualize the results. The Jadad score was used to assess the quality of the trials. Results We identified three RCTs [1,2,3] comparing patients treated with IMA 400 and IMA 800 and reporting on MMR at 12 months. Overall 1284 patients were included in the trial arms of interest - 554 were randomized into the IMA 400 arm and 730 into the IMA 800 arm. One trial used the Sokal and two used the Euro prognostic score as a stratum for randomization to allocate patients with different prognosis equally into the treatment arms. Percentage of Euro score high/intermediate risk patients in the IMA 800 arms was 14% / 49% in [1] and 49% / 30% in [3] and in the IMA 400 arms 12%/53% in [1] and 49%/31% in [3]. The percentage of Sokal score high/intermediate risk patients in [2] was 27%/34% in the IMA 400 arm and 23% / 35% in the IMA 800 arm. Median age of the patients in the IMA 400 / IMA 800 arms in [1,2,3] was 54/52, 45/48 and 50/52 years, respectively. Relative chance of being in MMR after 12 months of treatment in [1,2,3] was 1.78 (1.47 to 2.15), 1.15 (0.91 to 1.45) and 1.47 (1.01 to 2.14), respectively. The pooled estimate over all three studies was 1.45 (1.10 to 1.92) and thus indicates a significantly higher rate of MMR after 12 months by treatment with IMA 800 (Fig. 1, p = 0.0088). We identified four RCTs comparing IMA 400 to a TKI of the 2nd generation [4,5,6,7]. In [4] an IMA 400 arm was compared to treatment with two doses of 300mg nilotinib daily. Trials [5] and [7] each compared an IMA 400 arm with 100 mg/d of dasatinib, while [4] compared IMA 400 to 500mg of bosutinib daily. The percentage of Sokal high/intermediate risk patients in [4] and [6] was 28%/36% and 18%/ 47% in both the 2nd generation and the IMA 400 trial arm. Relative chance for MMR at 12 month for the respective 2nd generation TKI treatment arm compared to the IMA 400 arm was 2.00 (1.55 to 2.59) for [4] , 1.64 (1.24 to 2.17) for [5], 1.56 (1.22 to 2.00) for [6] and 1.34 (1.05 to 1.75) for [7]. The pooled estimate for the relative chance was calculated as 1.61 (1.37 to 1.91) (Fig. 2, p 〈 0.0001). All trials were rated with three out of five possible points on the Jadad scale; all were missing two points as none of the trials were blinded. However all trials were properly randomized and drop outs were well documented. Discussion The pooled estimate indicates a 45% higher probability of achieving MMR after 12 month with IMA 800 compared to IMA 400. This difference is statistically significant. Consequently, when choosing MMR at 12 months as primary endpoint, new therapies need to be compared with the IMA 800 regimen and not with the inferior IMA 400 therapy - as it is commonly done. The pooled efficacy estimates of the IMA 400 / IMA 800 and the IMA 400 / 2nd generation TKI trials cannot be compared directly. But given that the prognostic profiles of the patients of the different trials are fairly similar we can conclude that the MMR rates achieved with IMA 800 might be comparable to the ones achieved with 2nd generation TKIs as the confidence limits show a considerable overlap. [1] Hehlmann et al. 2011, JCO 29(12):1634-42. [2] Baccarani et al. 2014, IJH 99:616-24. [3] Deininger et al. 2011, BJH 164:223-32. [4] Sagl io et al. 2010, NEJM 362:2251-59. [5] Kantarjian et al. 2010, NEJM 362:2260-70. [6] Cortes et al. 2012, JCO 30(28):3486-92. [7] Radich et al. 2012, Blood 120(19):3898-905. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Hoffmann: Novartis Oncology Europe: Research Funding. Hasford:Novartis: Research Funding. Hehlmann:Novartis Pharma: Research Funding; BMS: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2787.2787

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: BMC Medicine, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2019-12)

Type of Medium: Online Resource

ISSN: 1741-7015

URL: Article

DOI: 10.1186/s12916-019-1360-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2131669-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1066-1066

Abstract: Despite recent advances, treatment of elderly patients with AML remains a challenge because of adverse disease biology, comorbidities and therapy related toxicities. The balance between effectivity and toxicity of treatment strategies play a key role. Since comparative studies are lacking, a prospective randomized trial was designed among German AML study groups with different treatment strategies to compare outcome. Patients ≥60 years with all AML subtypes except M3 were randomized up-front to a common standard arm (CSA) (10%) and to study specific arms (90%) of the AMLCG or the OSHO. The CSA consisted of one or two inductions of araC 100 mg/m2/d continuous IV (CI) d 1-7 d and daunorubicin (dauno) 60 mg/m2/d IV d 3, 4, 5 and two courses of araC 1 g/m2/d BID IV d 1, 3 and 5 as consolidation (Mayer RJ et al, NEJM 1994). The AMLCG study arm randomized TAD (araC 100 mg/m2/d CI d1-2 followed by BID d 3-8, dauno 60 mg/m2/d IV d 3-5 and 6-thioguanine 100 mg/m2/d po BID d 3-9) and HAM [araC 1 mg/m2/d IV BID d 1-3 and mitoxantrone (mito) 10 mg/m2/d IV d 3-5] versus two courses of HAM with any 2nd course only given if blasts persisted ± G-CSF. Two courses of TAD were given as consolidation followed by maintenance chemotherapy over three years. The OSHO study arm included araC 1 g/m²/d BID IV d 1 + 3 + 5 + 7 and mito 10 mg/m2/d IV d 1 - 3 for one or two induction courses and ara-C 500 mg/m² BID 1h IV d 1 + 3 + 5 in combination with mito10 mg/m2/d IV d 1 + 2 as consolidation. Pegfilgrastim 6 mg s.c. was applied on day 10 of induction and on d 8 of consolidation. The study was approved by the IRB and registered at clinicaltrials.gov (NCT01497002 and NCT00266136). Written informed consent was obtained from all patients prior to randomization. Between April 1st, 2005 and May 26th, 2015 1286 patients were assigned randomly to the CSA (n=132) or to the study groups arm (n=1154). After excluding 139 patients (10.8%), 1147 patients were eligible for analysis, 1120 with follow-up for overall survival (OS) and 1079 for complete remission (CR) analysis. Baseline characteristics of all eligible patients showed median ages of 68 (60-82) years for the CSA and 69 (60-87) and 70 (60-85) years in the study arms A and B, respectively (p=0.05). Proportions of patients with secondary AML differed significantly between study arms (A: 42%, B: 30%, CSA: 36%; p=0.003). The CSA had less flt3 wildtype/npm1 wildtype patients (31%) vs. arm A (51% p=0.040) and arm B (58%, p=0.0455). No differences were observed with respect to cytogenetic risk groups, white blood cell counts, LDH, and npm1 mutant/ flt3-wildtype or mutant. The primary endpoint event free survival (EFS) did not differ between the CSA and study group strategies. Three-year EFS was 12.4% (95% CI: 6.7 - 19.9%) in the CSA, 15.6% (95% CI: 13.1 - 18.3%) in group A and 11.4% (95% CI, 7.4% to 16.4%) in group B (n.s.;Fig.1). With a median follow-up of 67 months, OS did not differ significantly between CSA and study group regimens. The 3-year survival probability was 22.3% (95% CI: 14.7-30.9%) in the CSA, 24.7% (95% CI: 21.6-27.9%) in group A and 22.4% (95% CI, 16.7% - 18.3%) in group B (Fig.2). CR status after 90 days of therapy was evaluated as secondary endpoint. The proportion of patients in CR in the CSA [51% (95% CI: 42-61%)] was comparable to the 50% (95% CI: 47-54%) and 48% (95% CI: 41-55%) of the study group arms (p=n.s.). Persistent leukemia was seen in 16% (95% CI: 10-24%) in the CSA vs 17% (95% CI: 14-19%) and 12% (95% CI: 8-17%) in groups A and B, respectively (both p= n.s.). A total of 226 patients died within 90 days of treatment, 24% (95% CI: 17-33%) in CSA, 19% in group A (95% CI: 16-22%) and 27% (95% CI: 21-33%) in group B; CSA vs A p=0.1859, CSA vs B p=0.5902). Death without AML was 3% in CSA, 2% in group A and 3% in group B, death with AML was 9% in CSA, 6% in group A and 5% in group B and death from indeterminate cause was 12% in CSA, 11% in group A and 20% in group B. Three-year relapse free survival (RFS) was 21.3% (95% CI: 12.2 - 31.0) in the CSA, 28.9% (95% CI: 24.9 -33.0%) in group A and 24.0% (95% CI: 16.8 - 31.9) in group B (both p=n.s.; Fig.3). In multivariate analysis independent variables for EFS and OS were age, type of disease, cytogenetic group and WBC count, but not the allocation to one of the treatment arms. Age and cytogenetic group were determinants for RFS. Conclusion A strictly prospective comparison of different treatment strategies in patients with AML did not show clinically relevant outcome differences when compared to a common standard arm. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Niederwieser: Novartis Oncology Europe: Research Funding, Speakers Bureau; Amgen: Speakers Bureau. Hoffmann:Novartis Oncology Europe: Research Funding. Al-Ali:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Hegenbart:Pfizer: Other: Travel grant; Janssen: Honoraria, Other: Travel grant. Sayer:Riemser Pharma: Consultancy. Hochhaus:BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding. Fischer:Novartis: Consultancy, Honoraria. Dreger:Novartis: Consultancy; Janssen: Consultancy; Gilead: Consultancy; Gilead: Speakers Bureau; Roche: Consultancy; Novartis: Speakers Bureau. Hiddemann:Roche: Membership on an entity's Board of Directors or advisory committees; Genentech: Other: Grants; Roche: Other: Grants.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1066.1066

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: BMJ Open, BMJ, Vol. 9, No. 6 ( 2019-06), p. e028578-

Abstract: The POInT study, an investigator initiated, randomised, placebo-controlled, double-blind, multicentre primary prevention trial is conducted to determine whether daily administration of oral insulin, from age 4.0 months to 7.0 months until age 36.0 months to children with elevated genetic risk for type 1 diabetes, reduces the incidence of beta-cell autoantibodies and diabetes. Methods and analysis Infants aged 4.0 to 7.0 months from Germany, Poland, Belgium, UK and Sweden are eligible if they have a 〉 10.0% expected risk for developing multiple beta-cell autoantibodies as determined by genetic risk score or family history and human leucocyte antigen genotype. Infants are randomised 1:1 to daily oral insulin (7.5 mg for 2 months, 22.5 mg for 2 months, 67.5 mg until age 36.0 months) or placebo, and followed for a maximum of 7 years. Treatment and follow-up is stopped if a child develops diabetes. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies or diabetes. Other outcomes are: (1) Any persistent confirmed beta-cell autoantibody (glutamic acid decarboxylase (GADA), IA-2A, autoantibodies to insulin (IAA) and zinc transporter 8 or tetraspanin 7), or diabetes, (2) Persistent confirmed IAA, (3) Persistent confirmed GADA and (4) Abnormal glucose tolerance or diabetes. Ethics and dissemination The study is approved by the ethical committees of all participating clinical sites. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the trial. Trial registration number NCT03364868 .

Type of Medium: Online Resource

ISSN: 2044-6055 , 2044-6055

URL: Article

DOI: 10.1136/bmjopen-2018-028578

Language: English

Publisher: BMJ

Publication Date: 2019

detail.hit.zdb_id: 2599832-8

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2780-2780

Abstract: Introduction Clinical studies clearly show that treatment with tyrosine-kinase inhibitors (TKI) greatly improve the prognosis of patients with CML. Detailed treatment recommendations have since been deduced from clinical trial results by the European LeukemiaNet (Blood 122:872-884). However, little is known about whether these achievements can also be transferred to routine health care. This work investigates if all CML patients are treated in agreement with current standards and wether they achieve outcomes at least as good as those in clinical trials. Methods The web-based registry aimed to collect all newly diagnosed adult patients with chronic phase Ph+ and/or BCR-ABL1+ CML in 20 countries or pre-specified regions covering ~ 92.5 million inhabitants. Overall 2904 patients were registered between 2008 and 2012. Cytogenetic and molecular responses were analyzed using cumulative incidences considering death and progression as competing risks. Survival was analyzed using Kaplan-Meier curves and log rank tests. Results 2342 patients were diagnosed in chronic phase and had follow-up data available. The median age was 55 years (range: 18 to 99 years) and 53% were male; 11% of the patients were at high risk of not achieving complete cytogenetic remission (CCyR) at 18 months according to the EUTOS score. According to the Euro score 10% of the patients were in the high risk group, 51% in the intermediate and 39% in the low risk group. 18% were included in clinical trials. Treatment data of 1701 patients were contributed from 15 countries (85% of 2042 patients registered in those countries). As a first-line therapy 80% of patients received imatinib 15% nilotinib, 3% dasatinib and 3% hydroxyurea (HU). Of the patients receiving nilotinib or dasatinib 56% had been enrolled into clinical trials. There were no significant differences between female and male patients regarding the first-line therapy. More than half of the patients who were treated with HU alone were aged 70 or older. Time to first CCyR is known for 62% of patients. Median time to first CCyR was 10 months; after 12 months 57% (95% CI 54%-60%) and after 18 months 76% (95% CI 74%-79%) had achieved CCyR. Time to first CCyR differed significantly regarding the EUTOS score. Median time to first CCyR was 9 months for the low and 13 months for the EUTOS high risk group (p 〈 0.0001). After 18 months 78% (95% CI 75%-80%) of patients in the low and 69% (95% CI 60%-76%) of patients in the high risk group had achieved CCyR. The patients' age did not have major influence on the time to first CCyR (p=0.8974, median time to first CCyR: 18 to 39 years: 9 months, 40-65 years: 9 months, older than 65 years: 11 months). Time to first major molecular remission (MMR) could be calculated for 54% of patients. Median time to first MMR was 15 months. Cumulative incidence of MMR after 12 months was 41% (95% CI 38%- 44%). The median observation time of living patients was 29 months. 187 patients died (8%). Probability of OS for all patients at 12, 24 and 30 months was 97% (95% CI 96% - 97%), 94% (95% CI 93% - 95%) and 92% (95% CI 90% - 93%), respectively. 108 patients progressed of whom 62 subsequently died, while 125 patients died without prior progression. Probability of PFS for all patients at 12, 24 and 30 months was 95% (95% CI 94% - 96%), 92% (95% CI 91% - 93%) and 90% (95% CI 88% - 91%), respectively. Of the 187 patients who died, 33% died after progression. 67% died without prior progression. The probability of progression and subsequent death was 1% (95% CI 1% - 2%) after 12 months and 2% (95% CI 2% - 3%) after 24 months. The probability of dying without prior progression was 2% (95% CI 2% - 96%) after 12 months and 4% (95% CI 3% - 5%) after 24 months. Discussion The EUTOS population based registry provides the first unselected sample of adult Ph+ and/or BCR/ABL1+ adult CML patients in Europe. It shows that in Europe the success reported from commercial and academic studies is transferred to the general population. The majority of patients were treated first-line with imatinib, which was the only TKI approved for first-line use by the EMA during most of the registration period. Probabilities of PFS and OS in the registry are comparable to those in clinical trials. The importance of calculating both overall survival and leukemia-related survival is highlighted, since many patients die from different causes related or unrelated to leukemia and to treatment, but without progression. Disclosures Hoffmann: Novartis Oncology Europe: Research Funding. Baccarani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ARIAD Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hasford:Novartis: Research Funding. Lindoerfer:Novartis Oncology Europe: Research Funding. Burgstaller:Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; AOP Orphan Pharmaceuticals: Honoraria, Research Funding. Mayer:Novartis: Consultancy, Other: funding of travel, accomodations or expenses, Research Funding; BMS: Consultancy, Other: funding of travel, accomodations or expenses, Research Funding. Koskenvesa:GSK: Consultancy; Pfizer: Consultancy; Ariad: Other: funding of travel, accomodations or expenses; BMS: Consultancy, Other: funding of travel, accomodations or expenses; Novartis: Consultancy, Research Funding. Castagnetti:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Griskevicius:Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Sacha:Angelini: Consultancy; Adamed: Consultancy; Novartis: Consultancy; BMS: Consultancy. Hellmann:Novartis: Consultancy, Other: funding of travel, accomodations or expenses, Research Funding, Speakers Bureau; BMS: Consultancy, Other: funding of travel, accomodations or expenses, Speakers Bureau. Turkina:Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Novartis Pharma: Consultancy. Zaritskey:University of Heidelberg: Research Funding; Novartis: Consultancy. Sninska:Novartis: Consultancy. Simonsson:Novartis Pharma: Research Funding. Saussele:Novartis Pharma: Honoraria, Other: Travel grant, Research Funding; ARIAD: Honoraria; Pfizer: Honoraria, Other: Travel grant; BMS: Honoraria, Other: Travel grant, Research Funding. Hochhaus:ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Hehlmann:BMS: Consultancy; Novartis Pharma: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2780.2780

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2517-2517

Abstract: Background The German AML Intergroup conducted two randomized studies in younger ( 〈 60 years) and elderly (≥60 years) patients in which the study arms were compared to a common standard arm. Here, we compared the two studies in younger and elderly patients focusing on disease characteristics and outcome. Patients and Methods The East German Study Group (OSHO) and the Acute Myeloid Leukemia Cooperative Group (AMLCG) each entered patients from 18 to 59 years into one study and patients aged 60 years and older into another. Each study group randomized upfront 10% of all AML patients into a common standard arm and 90% in the study group specific arm. All patients with de novo AML or AML after myelodysplastic syndrome or cytotoxic treatment were eligible. Chi-squared and Mann-Whitney-U tests were used to detect significant differences between the age groups regarding demographic, clinical and cytogenetic characteristics at baseline. Complete Remission (CR) at 90 days and cumulative probabilities of death were determined for outcome. To avoid bias due to the higher probability of death in older patients, cumulative probabilities of death were calculated for relapsed patients or those who did not achieve CR after 90 days. Other deaths were considered as a competing risk. Results A total of 2435 AML patients were analyzed, 1132 in the study 〈 60 years and 1303 in the study ≥60 years. Significant differences in patient characteristics were noted between the studies. The elderly patient group contained a higher proportion of males than the younger group (55% vs 49% respectively, p=0.0031) and a higher percentage of secondary AML (40% vs 21% respectively, p 〈 0.0001). In contrast, younger patients had higher median WBC count [13x109/L (range 0.03-798) for 〈 60 years and 6.9x109/L (range 0.23-450) for ≥60 years, p 〈 0.0001] and higher median lactate dehydrogenase [442U/L (range 35-19,624) for 〈 60 years and 350U/L (range 51-9,486) for ≥60 years, p 〈 0.0001]. Cytogenetic risk was similarly distributed in both groups (favorable: 12% in both age groups, intermediate: 66% in 〈 60 years and 63% in ≥60 years, adverse: 22% in 〈 60 years and 25% in ≥60 years, p=0.1672). However, the favorable combination of FLT3-ITDwt and NPM1mut in normal karyotype was more common in the younger (35%) than in the older group (27%; p=0.0212). A higher rate of CR at 90 days was observed in the younger (66%) than in the older (51%) patients (p= 〈 0.0001). Of the younger patients 14.8% died (3.8% with persisting AML, 3.3% without AML and 7.7% without evaluable disease status) while of the older patients 21.8% died (6.2% with persisting AML, 2.5% without AML and 13.1% without evaluable disease status) during this period (p=0.0001). Relapse at 90 days was seen in 1% of the younger and in 2% of the older patients. The cumulative probability of AML-related death was lower in younger patients than in older patients (p 〈 0.0001). Of the younger patients 29% (95% CI: 26% to 31%) and 44% (95% CI: 40% to 46%) died after one and three years due to AML; in the older group the corresponding frequencies were 45% (95% CI: 42% to 48%) and 62% (95% CI: 59% to 65%; Figure 1a). The probability of dying from AML was lowest for the younger patients with de novo AML [27% (95% CI 24% to 29%) at 1 year and 41% (95% CI 38% to 44%) at 3 years] and highest for those with secondary AML [38% (95% CI 32% to 44%) at 1 year and 56% (95% CI 49% to 62%) at 3 years (p=0.0001)] , with similar differences being observed in the older patients (p=0.0001, Figure 1b). In the younger patients, CR at 90 days was lower in the standard (58%) than in the study arm (66%, p=0.0558), while AML related death was 29% and 27% at 1 year and 44% and 39% at 3 years respectively. In the older patients CR at 90 days was 52% vs. 51%, AML related death at 1 year 45% and 45% and at 3 years 63% and 69% for study arm and standard arm, respectively (Figure 1c). Conclusion This analysis reveals significant differences in gender, laboratory characteristics and proportion of secondary AML in elderly compared to younger AML patients. While there was no clear difference in cytogenetic risk groups, favorable molecular markers were more frequent in younger patients. Clear differences in CR rates after 90 days of therapy and AML related death rate were seen in regard to age ( 〈 60 years and ≥60 years) and disease type (de novo and secondary AML). As the common standard arm in both of the studies was age adapted, the differences between the two age groups are likely to be related to disease biology. Disclosures Niederwieser: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hoffmann:Novartis Oncology Europe: Research Funding. Krug:Sunesis; Clavis Pharma; usa Pharma, Catapult Cell Therapy, Gilead, Roche: Membership on an entity's Board of Directors or advisory committees; Sunesis: Speakers Bureau; Boehringer Ingelheim: Research Funding; Novartis; BMS; Roche; Boehringer Ingelheim; Bayer: Honoraria. Hegenbart:Janssen: Honoraria, Other: travel support. Pfirrmann:Novartis Pharma: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Kraemer:TEVA: Other: travel support. Al-Ali:Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2517.2517

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, Springer Science and Business Media LLC, Vol. 62, No. 10 ( 2019-10), p. 1276-1277

Type of Medium: Online Resource

ISSN: 1436-9990 , 1437-1588

URL: Article

DOI: 10.1007/s00103-019-03014-9

Language: German

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 1470303-8

SSG: 20,1

SSG: 8,1

In: Journal of Open Source Software, The Open Journal, Vol. 8, No. 82 ( 2023-02-21), p. 4545-

Type of Medium: Online Resource

ISSN: 2475-9066

URL: Journal

URL: Article

DOI: 10.21105/joss

DOI: 10.21105/joss.04545

Language: Unknown

Publisher: The Open Journal

Publication Date: 2023

detail.hit.zdb_id: 2891760-1