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  • 1
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2011, Vol.137(4), pp.733-738
    Description: Byline: Nils Winkelmann (1), Iver Petersen (2), Michael Kiehntopf (3), Hans Joerg Fricke (1), Andreas Hochhaus (1), Ulrich Wedding (1) Keywords: Geriatric assessment; Malignant lymphoma; Comorbidity; Survival; Prognostic value Abstract: Purpose The prevalence of elderly and comorbid patients (pts) with malignant lymphoma (ML) will steadily increase in future. Elderly patients comprise a heterogeneous population. Comprehensive geriatric assessment (CGA) is an established diagnostic tool in geriatric medicine. However, the prognostic value in patients with ML is unclear. We sought to establish a relationship between results of CGA and survival time in patients with ML. Methods Newly diagnosed patients with ML and indication for chemotherapeutical treatment were prospectively recruited in an observational trial. In addition to usual diagnostic work up, a CGA including activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities was performed. Association of patients' characteristics and results of CGA with survival were analysed according to Kaplan--Meier method and in a multivariate Cox-regression analysis. Results About 143 patients were included, median age was 63 years, 63 patients were women. Median follow-up of surviving patients was 62 months. Sixty-six patients died within this time. Advanced age, poor Karnofsky performance status, dependence in ADL and IADL and presence of severe comorbidity were significantly associated with shorter survival time. In a Cox-regression analysis, IADL (HR 2.1 95% CI 1.1--3.9) and comorbidity (HR 1.9 95% CI 0.9--3.9) were independent and strongest associated with survival time. Conclusion Results of CGA, such as IADL and comorbidities, are prognostic variables for survival of patients with ML. Results should be validated in homogeneous clinical groups and if confirmed included in diagnostic and therapeutic algorithm. Author Affiliation: (1) Klinik fur Innere Medizin II, Abteilung Hamatologie und internistische Onkologie, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany (2) Institut fur Pathologie, Universitatsklinikum Jena, Ziegenmuhlenweg 1, 07743, Jena, Germany (3) Institut fur Klinische Chemie und Laboratoriumsdiagnostik, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany Article History: Registration Date: 18/06/2010 Received Date: 27/05/2010 Accepted Date: 18/06/2010 Online Date: 03/07/2010
    Keywords: Geriatric assessment ; Malignant lymphoma ; Comorbidity ; Survival ; Prognostic value
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 2
    Language: English
    In: Annals of Hematology, 21 July 2010, Vol.90(4), pp.473-475
    Description: Dear Editor, We report on two patients with acute myeloid leukemia (AML) initially presenting in 2007. Both patients were tested positive for the FLT3-ITD mutation and were therefore treated with the FLT3 tyrosine kinase inhibitor sorafenib (400 mg/day) after progress of AML following several protocols of conventional chemotherapy. Both patients responded with a significant reduction of peripheral blast counts after 10 to 17 days leading to hematological response for 12 and 14 weeks, respectively. At the time of relapse, molecular analysis investigating mutations of both tyrosine kinase domains by sequencing of each individual FLT3-ITD cDNA did not demonstrate any additional mutations. We therefore suggest that the secondary resistance to sorafenib is mediated by other mechanisms than the acquisition of secondary mutations of FLT3 in these patients. FLT3-ITD mutations represent the second most frequent molecular aberration in AML leading to a constitutive activity of the class III receptor tyrosine kinase FLT3. FLT3-ITD mutations can be found in 25–30% of all AML patients and are associated with a reduced disease-free survival and overall survival [1–3].
    Keywords: Medicine ; Medicine
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 3
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2014, Vol.140(8), pp.1391-1397
    Description: Byline: Ulf Schnetzke (1), Peter Fix (3), Baerbel Spies-Weisshart (1), Karin Schrenk (1), Anita Glaser (2), Hans-Joerg Fricke (1), Paul Rosee (1), Andreas Hochhaus (1), Sebastian Scholl (1) Keywords: AML; Relapse; FLT3; Cyclophosphamide; Stem cell transplantation Abstract: Background Approximately, 70 % of adult patients with de novo acute myeloid leukemia (AML) achieve a complete remission (CR) while 10--20 % of AML are refractory to induction chemotherapy. Furthermore, a significant proportion of AML patients in CR will relapse during or after consolidation treatment. There is no evidence for a standard salvage regimen and most centers use a combination of an anthracycline and cytarabine (AraC). The aim of this study was to investigate the impact of two age-adjusted regimens containing AraC and cyclophosphamide applied for the treatment of relapsed or refractory AML. Patients and methods We retrospectively analyzed 60 patients (24 male, 36 female median age 56 years) with relapsed or refractory AML who were treated with a combination of AraC and cyclophosphamide monocentrically between October 2000 and January 2013. Two different protocols containing either high-dose (hAC) or intermediate-dose cytarabin (iAC) have been applied dependent on age and performance status. Results We demonstrate an overall response rate (CR + PR) induced by hAC and iAC of 56.7 %. Importantly, a complete remission rate (CR + CRp) of 52.2 % was found in patients who received the hAC regimen while only 8.8 % of patients achieved a CR following the iAC protocol (p 〈 0.001). The rate of refractory disease was 26.1 and 47.1 %, respectively. High-risk cytogenetics, i.e., a complex aberrant or monosomal karyotype had no effect on achievement of CR after hAC. In addition, there was no impact of activating FLT3 mutations on response to treatment according to the hAC regimen. In the cohort of patients treated with the iAC protocol, treatment-related mortality of 11.8 % within 60 days was observed but none of the patients who received the hAC regimen died within the first 2 months following chemotherapy. The toxicity profile was acceptable at both cytarabine dose levels. Importantly, 19 patients (82.6 %) of the hAC cohort underwent allogeneic hematopoietic stem cell transplantation (HSCT) as consecutive treatment. Conclusion The hAC regimen represents a promising therapeutic approach to induce a second CR in younger patients with relapsed or refractory AML prior to HSCT without using anthracyclines. Author Affiliation: (1) Abteilung Hamatologie und Internistische Onkologie, Klinik fur Innere Medizin II, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany (2) Institut fur Humangenetik, Universitatsklinikum Jena, Jena, Germany (3) Abteilung Internistische Onkologie und Hamatologie, Zentralklinik Bad Berka, Bad Berka, Germany Article History: Registration Date: 28/03/2014 Received Date: 12/03/2014 Accepted Date: 28/03/2014 Online Date: 12/04/2014 Article note: Ulf Schnetzke and Peter Fix have contributed equally to this work.
    Keywords: AML ; Relapse ; FLT3 ; Cyclophosphamide ; Stem cell transplantation
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 4
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2006, Vol.132(10), pp.665-671
    Description: Acute myeloid leukaemia (AML) is mainly affecting elderly patients. Elderly patients are increasingly affected by impairment of functional status (FS). FS is of prognostic relevance for survival in different tumours. Data for patients with AML are rare. Within a prospective trial we recruited patients with newly diagnosed AML and measured FS by two different methods: Karnofsky performance status (KPS) and instrumental activities of daily living (IADL). Sixty-three patients aged 19–85 years (median 61.1) were included. Twenty-three had prior myelodisplastic syndrome (MDS), 7 favourable, 17 unfavourable karyotype. Fifty received induction chemotherapy, 13 palliative chemotherapy. Median survival was 15.2 months (95% CI, 10.8–22.3) in all patients. Age, cytogenetic risk group, and impaired KPS and IADL significantly influenced median survival in univariate analysis. Impairment of IADL was the single most predictive variable. In multivariate analysis, impairment of IADL Score (HR:4.3, 95% CI 1.7–10.5, P  = 0.001) and of KPS (HR:4.8, 95% CI 1.9–12.3, P  = 0.001), and unfavourable cytogenetic risk group (HR:6.0, 95% CI 2.5–14.3, P  〈 0.001) significantly predicted median survival. In patients with AML, FS and not age is a major predictor of survival. The influence of FS is independent from cytogenetic risk group. IADL measurement adds information to KPS. The results have to be confirmed in a large sample of patients.
    Keywords: Acute myeloid leukaemia ; Functional status ; Chemotherapy ; Geriatric assessment ; Survival
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 5
    Language: English
    In: Oncology Reports, January 2004, Vol.11(1), pp.89-92
    Description: We report on a 72-year-old patient with a clinically diagnosed plasmocytoma which developed to a plasma cell leukemia (PCL) with so far unrecorded complex translocations. As GTG-banding was not able to resolve all karyotypic changes, multiplex-fluorescence in situ hybridization (M-FISH) in combination with microdissection based comparative genomic hybridization (micro-CGH) and multicolor banding (MCB) have been done. Using these molecular cytogenetic approaches the karyotype of the PCL case can be described as: 51,XY,-1,-1,+3,+der(5)t(5;11;1)(5pter↷5q13-q14::11q24↷11q25::1q12↷1qter),+7 or +der(7)t(7;1)(7qter↷7p15::1p31.1↷1pter),+8,+der(9)t(1;9)(1qter↷1q12::9q12↷9pter),der(11)t(1;11;1)(1pter↷1p31.1::11p15.5↷11q25::1q12↷1qter),-13,der(14)t(X;14)(Xqter↷Xq21.3::14pter↷14qter),+15,+18,der(19)t(9;19)(9qter↷9q12::19q11↷19pter),+i(19)(q10). The case shows one of the most complex karyotypic rearrangements ever described in PCL and indicates two additional chromosomal regions which may contain genes of interest for the development of this hematological disorder: loss of 1p10-p31.1 material and gain of Xq21.3-qter.
    Keywords: Translocation, Genetic ; Leukemia, Plasma Cell -- Genetics;
    ISSN: 1021-335X
    E-ISSN: 17912431
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  • 6
    Language: English
    In: International journal of oncology, February 2009, Vol.34(2), pp.417-23
    Description: Acute myeloid leukemia (AML) is a heterogeneous disease with respect to clinical prognosis and acquired chromosomal aberrations. After routine banding cytogenetic analysis 45% of AML patients show a normal karyotype (NK-AML). For a better understanding of development and progression in AML, it is important to find markers which could be primary genetic aberrations. Therefore, in this study 31 patients with NK-AML were analyzed by new high resolution molecular cytogenetic approaches. A combination of multitude multicolor banding and metaphase microdissection-based comparative genomic hybridization revealed deletions of the subtelomeric regions in 6% of the studied cases. According to these results, locus-specific probes for the subtelomeric regions of chromosomes 5, 9, 11, 12 and 13 were applied on 22 of the studied 31 NK-AML cases. Surprisingly, 50% of them showed deletions or duplications. These aberrations occurred in the in vitro proliferating as well as in the non-proliferating cells. Meta-analysis of the aberrant regions revealed that they often include genes known to be associated with tumors, e.g. RASA3 on chromosome 13. These results implicate that aberrations in the subtelomeric regions of NK-AML occur quite often and may be considered as primary genetic changes, and should not be neglected in future diagnostic approaches.
    Keywords: Chromosome Aberrations ; Leukemia, Myeloid, Acute -- Genetics ; Telomere -- Genetics
    ISSN: 1019-6439
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  • 7
    In: European Journal of Haematology, March 2008, Vol.80(3), pp.208-215
    Description: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3‐ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3‐ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. We retrospectively analysed the prevalence of NPM1 and Flt3‐ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60–85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow‐up of surviving patients was 600 d. Sixty‐seven patients were tested negative for NPM1 and Flt3‐ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3‐ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2,  = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log‐rank test  = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3‐ITD mutation had a significant worse overall survival compared to wildtype patients ( = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%,  = 0.91). As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose‐reduced conditioning) should be considered for these patients in first CR.
    Keywords: Aml ; Npm1 ; Flt3‐Itd ; Elderly Patients ; Prognosis
    ISSN: 0902-4441
    E-ISSN: 1600-0609
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  • 8
    Language: English
    In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 10 September 2009, Vol.27(26), pp.4378-84
    Description: This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). Patients (〈or= 75 years of age) were randomly assigned to receive bendamustine 100 mg/m(2)/d intravenously on days 1 to 2, or chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P 〈 .0001). More patients showed complete responses with bendamustine than with chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P 〈 .0001). Bendamustine was also associated with an improvement in duration of remission, compared with chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients. Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.
    Keywords: Chlorambucil -- Therapeutic Use ; Leukemia, Lymphocytic, Chronic, B-Cell -- Drug Therapy ; Nitrogen Mustard Compounds -- Therapeutic Use
    E-ISSN: 1527-7755
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