Barbara Deschler

Universitätsklinikum Freiburg, Freiburg, Lower Saxony, Germany

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Publications (10)47.05 Total impact

  • Article: Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome.
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    ABSTRACT: Background. Myelodysplastic syndromes and acute myeloid leukemia exemplify the complexity of treatment allocation in older patients as options range from best supportive care, non-intensive treatment (e.g. hypomethylating agents) to intensive chemotherapy/hematopoietic cell transplantation. Novel metrics for non-disease variables are urgently needed to help define each older patient's best treatment. Design and Methods. We investigated the feasibility and prognostic value of geriatric/quality of life assessments aside from established disease-specific variables. 195 patients ≥60 years with myelodysplastic syndromes/acute myeloid leukemia were assessed, grouped according to treatment intensity. The assessment consisted of eight instruments evaluating activities of daily living, depression, mental functioning, mobility, comorbidities, Karnofsky Index and quality of life. Results. Patients with a median age of 71 years (60-87) with myelodysplastic syndromes (n=63) or acute myeloid leukemia (n=132) were treated either with best supportive care (n=47), hypomethylating agents (n=73) or intensive chemotherapy/hematopoietic cell transplantation (n=75). After selection of variables, pathological activities of daily living and quality of life/fatigue remained highly predictive for overall survival in the entire patient group beyond disease-related risk factors adverse cytogenetics and blast count ≥20%. In 107 patients treated non-intensively activities of daily living<100 (Hazard Ratio:2.94), Karnofsky Index<80 (Hazard Ratio:2.34) and quality of life/fatigue≥50 (Hazard Ratio:1.77) were significant prognosticators. Summation of adverse features revealed a high risk of death (Hazard Ratio: 9.36). Conclusions. In-depth evaluation of older patients prior to individual treatment allocation is feasible and adds information to standard assessment. Patients ≥60 years with newly diagnosed myelodysplastic syndromes/acute myeloid leukemia and impairments in activities of daily living, Karnofsky Index of <80%, quality of life/fatigue≥50 are likely to have poor outcomes.
    Haematologica 08/2012; · 6.42 Impact Factor
  • Article: NT-pro-BNP: not the prognostic all-rounder in elderly patients undergoing allogeneic stem cell transplantation.
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) is a curative approach for several diseases predominantly affecting elderly patients. Overall survival is compromised by treatment-related mortality (TRM), GvHD, and relapse. Pretransplant clinical risk indicators in elderly patients qualifying for HCT are highly desirable. Pro-BNP is known as a predictor of death in patients with an increasing variety of clinical conditions and frequently used as a routine parameter for organ complications in the allogeneic transplant setting without well-established scientific evidence. Our hypothesis was that pre-HCT NT-pro-BNP could aid in identifying elderly patients at risk for early mortality. We retrospectively evaluated NT-pro-BNP values in 177 consecutive patients of ≥60 years HCT (2005-2010). In 29.4 % of cases, NT-pro-BNP values were within our institute's normal range (<125 pg/ml). Analysis of different NT-pro-BNP cutoff points by receiver operating characteristics curve for mortality at day +100 revealed no single cutoff value with satisfying specificity and sensitivity. The individual outcome of patients with extremely high NT-pro-BNP values was not associated with an increase in mortality or cardiovascular morbidity. NT-pro-BNP values of patients succumbing to TRM did not differ significantly from those alive or having died of relapse-median 276 vs. 217 pg/ml. In conclusion, pre-HCT NT-pro-BNP was of no convincing prognostic relevance for day 100 mortality.
    Annals of Hematology 07/2012; · 2.62 Impact Factor
  • Article: A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy.
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    ABSTRACT: The treatment of acute myeloid leukemia of older, medically non-fit patients still poses a highly unmet clinical need, and only few large, prospective studies have been performed in this setting. Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine (decitabine) in myelodysplastic syndromes and acute myeloid leukemia with 20-30% bone marrow blasts, we investigated whether this drug is also active in patients with more than 30% blasts. To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy, 227 patients (median age, 72 years), many with comorbidities, adverse cytogenetics and/or preceding myelodysplastic syndrome were treated with this hypomethylating agent. During the initial decitabine treatment (135 mg/m(2) total dose infused intravenously over 72 hours every 6 weeks), a median of two cycles was administered (range, 1-4). All-trans retinoic acid was administered to 100 patients during course 2. Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses (range, 1-19) with a lower dose of decitabine (20 mg/m(2)) infused over 1 hour on 3 consecutive days every 4-6 weeks. The complete and partial remission rate was 26%, 95% CI (20%, 32%), and an antileukemic effect was noted in 26% of patients. Response rates did not differ between patients with or without adverse cytogenetics; patients with monosomal karyotypes also responded. The median overall survival from the start of decitabine treatment was 5.5 months (range, 0-57.5+) and the 1-year survival rate was 28%, 95%CI (22%,34%). Toxicities were predominantly hematologic. Decitabine is well tolerated by older, medically non-fit patients with acute myeloid leukemia; myelosuppression is the major toxicity. The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome. Because of these encouraging results, randomized studies evaluating single-agent decitabine versus conventional treatment are warranted. The study is registered with the German Clinical Trials Registry, number DRKS00000069.
    Haematologica 11/2011; 97(3):393-401. · 6.42 Impact Factor
  • Article: Prognostic factor and quality of life analysis in 160 patients aged > or =60 years with hematologic neoplasias treated with allogeneic hematopoietic cell transplantation.
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    ABSTRACT: Toxicity-reduced conditioning is a curative treatment option for medically compromised or elderly patients ineligible for myeloablative hematopoietic cell transplantation (HCT). The aim of this study was to detect prognostic factors for overall survival (OS) and to evaluate quality of life (QOL) in a large homogeneous cohort of 160 consecutive patients aged > or =60 years treated with allogeneic HCT. We evaluated age, sex, performance status, comorbidities, pulmonary function, lactic dehydrogenase concentration, type of donor, disease status, CD34(+) cells transplanted, cytomegalovirus status, time from diagnosis to HCT, and the development of acute and chronic graft-versus-host disease (GVHD). All patients who survived for > or =6 months (n = 79) were asked to complete a QOL survey. All patients (median age, 64.7 years; range, 60.1-76 years) received pretransplantation conditioning with fludarabine, BCNU, and melphalan. With a median follow-up of 35 months, the 1-year OS was 62.4% and 3-year OS was 47.4%. Multivariate analysis revealed compromised performance status as the most significant negative prognostic parameter for OS (P < .003), whereas male donor (P = .008) and chronic GVHD (P = .024) were associated with better OS. The 89% of survivors who returned the QOL questionnaire rated their global QOL as good-to-excellent despite impaired functional capabilities and such symptoms as fatigue, dyspnea, and loss of appetite. The main prognostic factor was performance status, not age. Our data suggest that toxicity-reduced conditioning offers a chance for enhanced OS with an adequate QOL.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2010; 16(7):967-75. · 3.15 Impact Factor
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    Article: Valuation of transfusion-free living in MDS: results of health utility interviews with patients.
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    ABSTRACT: This study measured how myelodysplastic syndrome (MDS) patients value transfusion independence (TI), reduced transfusions (RT) and transfusion-dependence (TD) using health utility assessment methodology. 47 MDS patients were interviewed, US (n = 8), France (n = 9), Germany (n = 9) and the UK (n = 21), to elicit the utility value of TI, RT and TD. Health states were developed based on literature; patient forum discussions; and were validated by a hematologist. Face-to-face interviews used the feeling thermometer Visual Analogue Scale (VAS) and the Time Trade-Off (TTO) method to value the health states on a 0 (dead) to 1 (perfect health) scale. Socio-demographic, clinical, and quality-of-life (EQ-5D) characteristics were surveyed to describe the patient sample. The mean age was 67 years (range: 29-83); 45% male, 70% retired; 40% had secondary/high school education, or higher (32%), and 79% lived with family, a partner or spouse, or friends. The mean time from MDS diagnosis was 5 years (range:1-23). Most patients (87%) received previous transfusions and 49% had received a transfusion in the last 3 months. Mean EQ-5D index score was 0.78; patients reported at least some problem with mobility (45%), usual activities (40%), pain/discomfort (47%), and anxiety/depression (34%). Few patients had difficulty understanding the VAS (n = 3) and TTO (n = 4) exercises. Utility scores for TI were higher than for RT (0.84 vs. 0.77; p < 0.001) or TD (0.84 vs. 0.60; p < 0.001). Three patients rated TD worse than dead. Corresponding VAS scale scores were 78 vs. 56; (p < 0.001), and 78 vs. 31 (p < 0.001), respectively. Patients value TI, suggesting an important role for new treatments aiming to achieve greater TI in MDS. These results can be used in preference-based health economic evaluation of new MDS treatments, such as in future cost-utility studies.
    Health and Quality of Life Outcomes 09/2009; 7:81. · 2.11 Impact Factor
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    Article: Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: problems and approaches.
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    ABSTRACT: High-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are mainly diseases of patients over the age of 60 years. In these patients, intensive chemotherapy and/or allogeneic blood stem cell transplantation are the only curative treatment approaches, while non-curative options include low-dose chemotherapy or best supportive care alone. The basis for treatment decision-making in this clinically and biologically heterogeneous group is not well defined. In order to investigate treatment stratification patterns and outcomes in this population, we performed a systematic literature search in MedLine for relevant clinical reports published between 1989 and 2006. Only large population-based investigations and publications of clinical trials with more than 40 patients were analyzed. In 36 AML studies involving a total of 12,370 patients (median age 70 years) median overall survival approached 30 weeks for intensively treated patients. In patients receiving best supportive care alone, or best supportive care plus non-intensive treatment, median overall survival was 7.5 and 12 weeks, respectively. The complete remission rate after induction was 44%, and in those patients who achieved complete remission age no longer influenced prognosis. In 18 large studies approximately 50% of AML patients received induction therapy, 30% non-intensive chemotherapy and 20% supportive care only. Due to the scarcity of randomized AML/MDS trials in which older patients are assigned to either induction or less intense therapy, predictors to identify older patients most likely to benefit from intensive therapy and novel tools to optimize (or even standardize) recommendations are needed. We propose that in this patient population in the future, geriatric assessment instruments and comorbidity scoring are implemented in treatment decision-making.
    Haematologica 12/2006; 91(11):1513-22. · 6.42 Impact Factor
  • Article: Acute myeloid leukemia: epidemiology and etiology.
    Barbara Deschler, Michael Lübbert
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    ABSTRACT: Acute myeloid leukemias (AMLs) are infrequent, yet highly malignant neoplasms responsible for a large number of cancer-related deaths. The incidence has been near stable over the last years. It continuously shows 2 peaks in occurrence in early childhood and later adulthood. With an incidence of 3.7 per 100,000 persons and an age-dependent mortality of 2.7 to nearly 18 per 100,000 persons, there is a rising awareness in the Western world of AML's special attributes resulting from an ever-aging population. To objectively describe epidemiologic data on this patient population, recent publications were evaluated to make transparent the current trends and facts. A review of the literature is presented, reflecting highlights of current research with respect to AML etiology. To estimate outcome and discuss informed treatment decisions with AML patients of different age groups and different biologic risk categories, it is mandatory to consider that the outcome results reported in clinical trials were until now heavily biased toward younger patients, whereas the overall dismal prognosis documented in population-based studies most likely reflects the exclusion of older patients from aggressive treatment. The etiology for most cases of AML is unclear, but a growing knowledge concerning leukemogenenic agents within chemotherapy regimens for other malignancies is already available. This includes specific associations of the most frequent balanced translocations in AML, including the "good-risk" abnormalities comprised by the core binding factor leukemias (i.e., AML with the translocation (8;21) and inversion of chromosome 16, and acute promyelocytic leukemia with the translocation (15;17)). In contrast to these genetic alterations, epigenetic lesions, e.g., promoter silencing by hypermethylation of the p15/INK4b and other genes, are increasingly recognized as important in the pathogenesis of AML.
    Cancer 12/2006; 107(9):2099-107. · 4.77 Impact Factor
  • Article: Striking complete remission after interferon-alpha for secondary recurrent non-Hodgkin's lymphoma but rare interferon-induced side effects.
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    ABSTRACT: Interferon (IFN) treatment is a therapeutic option in the treatment of non-Hodgkin's lymphoma (NHL). Although randomized trials have failed to show significant differences in progression-free and overall survival (OS) with IFN compared to placebo after peripheral blood stem cell transplantation (PBSCT) as well as standard therapy for NHL, anecdotal case reports have documented impressive results in selected patients. With this case report, we demonstrate an astounding success of IFN therapy given in the treatment of a young man with second relapse after two consecutive autologous PBSCTs and abdominal irradiation. With occurrence of multiple lymph node enlargements despite this intensive treatment, he received IFN and obtained a well-documented complete remission (CR). Yet, treatment with IFN always has to be considered in the context of its significant side effect profile, which can have considerable impact on the patient's quality of life as illustrated in this case report.
    Annals of Hematology 05/2005; 84(4):263-6. · 2.62 Impact Factor
  • Article: Striking complete remission after interferon-α for secondary recurrent non-Hodgkin’s lymphoma but rare interferon-induced side effects
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    ABSTRACT: Interferon (IFN) treatment is a therapeutic option in the treatment of non-Hodgkins lymphoma (NHL). Although randomized trials have failed to show significant differences in progression-free and overall survival (OS) with IFN compared to placebo after peripheral blood stem cell transplantation (PBSCT) as well as standard therapy for NHL, anecdotal case reports have documented impressive results in selected patients. With this case report, we demonstrate an astounding success of IFN therapy given in the treatment of a young man with second relapse after two consecutive autologous PBSCTs and abdominal irradiation. With occurrence of multiple lymph node enlargements despite this intensive treatment, he received IFN and obtained a well-documented complete remission (CR). Yet, treatment with IFN always has to be considered in the context of its significant side effect profile, which can have considerable impact on the patients quality of life as illustrated in this case report.
    Annals of Hematology 03/2005; 84(4):263-266. · 2.62 Impact Factor
  • Article: Acquired high-titer factor VIII inhibitor: fatal bleeding despite multimodal treatment including rituximab preceded by multiple plasmaphereses.
    Blood 06/2003; 101(9):3753-4; author reply 3754-5. · 9.90 Impact Factor