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In: Leukemia & Lymphoma, Informa UK Limited, Vol. 54, No. 11 ( 2013-11), p. 2458-2465

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.3109/10428194.2013.778406

Language: English

Publisher: Informa UK Limited

Publication Date: 2013

detail.hit.zdb_id: 2030637-4

In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 92, No. 1 ( 2013-1), p. 25-32

Type of Medium: Online Resource

ISSN: 0939-5555 , 1432-0584

URL: Article

DOI: 10.1007/s00277-012-1569-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2013

detail.hit.zdb_id: 1458429-3

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3163-3163

Abstract: Abstract 3163 Background: Fatigue can potentially compromise activities of daily living and functional abilities in patients with myelodysplastic syndromes (MDS). These patients typically also have a limited life expectancy, thus making the improvement of health-related quality of life an important goal of therapy. However, there is paucity of evidence-based data in this area. Aims: To investigate the relationships between fatigue and physical, social and emotional functions in high-risk MDS patients and to evaluate socio-demographic and clinical characteristics associated with fatigue. Methods: Newly diagnosed patients with intermediate-2 or high-risk IPSS score are recruited in an international prospective observational study. Current analysis is based on patients recruited in 37 centers. A number of socio-demographic, clinical and laboratory variables were collected prior to treatment. Also, fatigue and functional abilities were measured before treatment start. Fatigue was evaluated with the FACIT-Fatigue scale. This is a simple 13-item psychometrically robust questionnaire that assesses self-reported tiredness, weakness and difficulty conducting usual activities due to fatigue. Functional abilities and quality of life (QoL) were assessed with the EORTC QLQ-C30. Both questionnaires have undergone rigorous linguistic cross-cultural validation and were available for all patients in the appropriate language. Functional aspects investigated included: physical (PF), role (RF), emotional (EF), cognitive (CF) and social functioning (SF). These scales range from 0 to 100, with higher scores representing better outcomes. Based on previous research, 10-points were considered to be a minimally important difference (MID) for the functional and QoL scales investigated. A score difference at least equal to MID was considered as a clinically meaningful difference. The cohort was divided into four groups based on the FACIT-Fatigue scores quartiles and patients were defined as having low, low/medium, medium/high and high fatigue levels. All variables investigated were summarized according to fatigue levels. Associations between fatigue levels and functional aspects, socio-demographic characteristics (i.e., age, gender, living arrangements, education) and clinical data (i.e., performance status and IPSS risk) were investigated using Chi-square and Kruskall-Wallis tests as appropriate. Multivariate stepwise regression analysis was also performed to investigate the impact of self-reported fatigue on functional scales. Results: Analysis is based on 240 patients, of whom 77% and 23% respectively classified with intermediate-2 and high-risk IPSS score. Median age of patients was 71 years (36% female and 64% male) and 49% had at least one comorbidity. Seventy-three percent of patients had an ECOG performance status ≥1. Patients with higher levels of fatigue reported worse scores in all functional aspects investigated. PF, RF and SF scales were found to be the most compromised aspects by fatigue severity. Mean score differences, between patients reporting low versus high fatigue levels were not only statistically significant (P 〈 .001), but also clinically meaningful being respectively: 45, 54 and 43 points for the PF, RF and SF scales. Also, higher fatigue was associated with poorer QoL outcomes. Mean scores of patients with low versus high levels of fatigue were respectively: 70 (SD 19,1) and 31.2 (SD, 22.8). Mean score difference, between patients reporting low versus high fatigue levels were also statistically significant (P 〈 .001) and clinically meaningful being of 39 points. Multivariate analyses showed that the association between fatigue and all functional aspects and QoL was independent of age, gender, education, time from diagnosis and transfusion dependency. Investigation of possible determinants of fatigue severity revealed that this was not significantly associated with age, gender, IPSS risk category, WHO classification, comorbidity and living arrangements. Conclusion: This study suggests that fatigue is the major factor greatly compromising functional abilities and QoL in high-risk MDS patients before treatment. Successfully treating fatigue is crucial to improve functional abilities in these patients and to maximize treatment outcomes. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.3163.3163

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2927-2927

Abstract: Abstract 2927 Background: Immunological changes have a primary role in the initiation and progression of myelodysplastic syndromes (MDS). Cytokine levels, such as IL-7 and IFN-gamma, are associated with lower-risk disease. Treatment with lenalidomide has proven efficacy in red blood cell (RBC) transfusion-dependent lower-risk MDS patients with del(5q). Lenalidomide exerts anti-angiogenic, anti-proliferative, and pro-erythropoietic effects; in particular, it has been shown that lenalidomide inhibits the proliferation and function of T regulatory cells (Tregs). Finally, MDS patients undergoing lenalidomide treatment experience erythroid responses and suppression of the del(5q) clone. Aims: In a multicenter Italian phase II trial to evaluate safety and efficacy of lenalidomide in primary MDS patients with del(5q) and Low- or Int-1 risk IPSS, we investigated changes in the transcription of cytokines and their receptors during treatment. Methods: The starting dose of lenalidomide was 10 mg p.o once daily on a continuous daily schedule for a maximum of 12 months. Bone marrow (BM) aspirates were obtained on study entry and every 12 weeks. Assays were performed using TaqMan® Low Density Array Fluidic card (TaqMan® Human Array, Applied Biosystems, Foster City, CA, USA) based on Applied Biosystems PRISM® 7900HT comparative ddCT method, according to the manufacturer's instructions. Target gene expression levels were measured in triplicate and normalized against the expression of the 18S housekeeping gene from a BM pool of normal, healthy subjects at all timepoints. Median relative gene expression values in MDS patients were compared to healthy subjects, set as a value of 1. Results: We report data obtained at baseline and after 12 weeks. Informed consent was obtained in all patients. Twenty-seven patients (5 M, 22 F) were evaluated at baseline and after 12 weeks. Mean age was 72 ± 9 years. Mean Hb level was 8.5 ± 0.9 g/dL and 16 patients were RBC transfusion -dependent (requiring at least 4 RBC transfusions in the preceding 2 months). Seven patients had additional cytogenetic abnormalities. Twenty-one patients (80%) experienced erythroid responses by week 12. Significant variations in gene expression of cytokines and receptors were observed during treatment. Genes significantly regulated during lenalidomide treatment (P 〈 0.05) are shown in the Table. In particular, FAS, IL-7 and FOXP3 gene were generally under-expressed at baseline and significantly increased after 12 weeks. Accordingly, IL7R was over-expressed in all patients at baseline and its expression was significantly reduced during treatment. Furthermore, IFN-gamma expression increased during therapy. Summary: The protein encoded by FAS gene is a member of the TNF-receptor superfamily and its interaction with its ligand leads to apoptosis. Interleukin (IL)-7 is an essential cytokine that promotes the proliferation and survival of B- and T-lymphocyte progenitors. The IL7R gene on chromosome 5 (5p13) codifies for the IL7 receptor, which blocks apoptosis during differentiation and activation of T lymphocytes. It functions, in part, through the induction of the expression of the antiapoptotic protein Bcl-2. The protein encoded by the FOXP3 gene is a member of transcriptional regulators. Defects in this gene are the cause of X-linked autoimmunity-immunodeficiency syndrome. The results of the present study indicate that lenalidomide may act through immunological changes. Further detailed analyses in these patients may provide new insights into the pathogenesis of MDS with del(5q) and the long-term effects of lenalidomide treatment on immunological changes in BM cells. Disclosures: Oliva: Celgene: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.2927.2927

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 47-48

Abstract: Introduction Tyrosine kinase inhibitors (TKIs) have dramatically changed the outcome of chronic phase chronic myeloid leukemia patients (CP-CML),improving the long-term outcome; indeed, life expectancy is now very close to that of age matched individuals in the general population. Imatinib (IMA) the first generation TKI, increased the overall survival(OS)by more than 80%. Second-generation TKIs, (2gen TKIs) used in first line dasatinib and nilotinib, induced faster molecular responses, rapidly reducing the disease burden, but did not change the OS of CP-CML newly diagnosed patients. Most of the available data reported were extrapolated from sponsored clinical trials. The aim of this analysis is to detail and analyze the prognostic features influencing the OS in a large Italian CML cohort of patients prospectively enrolled in the GIMEMA CML Italian study. Methods Relevant clinical, demographic, biological and treatment-related information were web-based collected during a multicenter,observational Italian study that enrolled consecutive patients in each disease phase, at 68 Italian hematologic centers belonging to the GIMEMA network from January 2013 to June 2020. We analyzed prognostic factors influencing the OS by Kaplan Meier method and Cox multivariable models. Results A cohort of 1206 patients was prospectively analyzed, 608 of them received frontline IMA and 598 2genTKIs. Median age in the IMA cohort was 69 years (range 58-77) vs 52 years in the 2genTKIs cohort (range 41-63). The male/female ratio was 1.7 in the IMA group and 1.35 in the 2genTKIs cohort. Ninety-eight percent of patients were in CP. Results of molecular analysis of the BCR-ABL transcript at baseline showed: b2a2 in 33.1 % of patients and b3a2 in 59.9%, while an atypical transcript was found in 7%. The cytogenetic analysis at baseline showed major and minor additional aberrations in 5.7% and 1.6% of patients respectively. In the IMA cohort,according to the Sokal score, 27.7%, 57.3% and 15% of patients were stratified as low, intermediate and high risk, whereas according to the ELTS score 51.3%, 35.5% and 13.3%, of patients were classified as low, intermediate and high risk. In the 2genTKIs cohort, according to the Sokal score, 44.8%, 34.5% and 20.8%, were low, intermediate and high risk, respectively, whereas according to the ELTS score, 66.9%, 22% and 11% were assigned to the respective risk groups.The Charlson comorbidity index in the IMA cohort was 2-3 and 4-5 in 74% and 26% of patients respectively; in the 2genTKIs cohort the score was 2-3 in 89% and 4-5 only in 10% of patients. Overall, median follow-up of the whole population was 24.7 months (range 13.3-39.3).Seventy-three patients (6.1%) in the overall population died, the majority of them in the IMA cohort: 56 patients (9.2%), at median age of 80.5 years,11/608 (1.8%) due to CML-related causes. Conversely,in the 2genTKIs cohort only 17 patients (2.8%) died, at a median age of 62 years, 10/598 (1.7%) for CML-related causes. Estimated 60-months OS of the overall population was 86.4% (95% CI 81.3-90.2): 75.8% (95% CI 64.5-84) in the IMA cohort and 93.8% (95% CI 87.5-97) in the 2genTKIs group (p & lt;0.0001). The ELTS score provides a better stratification of 60 months OS both in the IMA (OS 60-months 91.4%, 65.2%, 48.7% in low, intermediate and high risk, p & lt;0.0001) (Fig.1a) and the 2genTKIs subgroups (OS 60-months OS 95.4%, 92%, 87.9% in low, intermediate and high risk, p=0.0013)(Fig.1b). An adjusted Cox model on the entire population showed that prognostic factors influencing OS are: ELTS score (high risk vs low HR= 5.2, 95%CI 2.7-10.03, p & lt;0.0001),the type of TKI (2genTKIs vs IMA HR= 0.46; 95% CI 0.24-0.87, p=0.018), age (HR=1.03 per year, 95%CI 1.00-1.05, p=0.025) and the Charlson index (4-5 vs 2-3, HR= 1.75, 95%CI 1.43-2.1, p & lt;0.0001). Conclusions In this first analysis of our study different clinical behaviors were observed among Italian hematologists, who prevalently prescribed IMA to older patients,with more comorbidities, as compared to 2genTKIs.These differences explain a better OS for patients treated with 2genTKIs vs IMA, however, the risk of death for CML related causes is quite similar between the two groups, all the differences being attributable to other causes of death.Prognostic baseline features associated to an increased OS confirmed that, in addition to age, the ELTS score and the comorbidities are the main clinical factors that independently influence the long-term OS Disclosures Pregno: Incyte-Italy,: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Novartis-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Pfizer-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports. Breccia:Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy. Castagnetti:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Galimberti:Novartis: Speakers Bureau; Incyte: Honoraria. Bocchia:CELGENE: Honoraria; Incyte: Honoraria. Abruzzese:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Levato:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rosti:Pfizer: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Di Raimondo:GILEAD, Incyte: Research Funding; Amgen, Takeda, Novartis: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Pane:Janssen: Other: Travel Expenses; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis pharma SAS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: travel expenses, Speakers Bureau; Daiichi Sankyo: Consultancy, Other: Travel Expenses; Amgen: Consultancy, Other: Travel Expenses, Speakers Bureau; AbbVie: Consultancy, Other: Travel Expenses, Speakers Bureau. Foà:Incyte: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Saglio:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Roche: Research Funding; Novartis: Research Funding; Ariad: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-139307

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e44846cb-

Type of Medium: Online Resource

ISSN: 2572-9241

URL: Article

DOI: 10.1097/01.HS9.0000977356.44846.cb

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2023

detail.hit.zdb_id: 2922183-3

In: SSRN Electronic Journal, Elsevier BV

Type of Medium: Online Resource

ISSN: 1556-5068

URL: Article

DOI: 10.2139/ssrn.4313690

Language: English

Publisher: Elsevier BV

Publication Date: 2022

In: American Journal of Hematology, Wiley, Vol. 98, No. 8 ( 2023-08)

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v98.8

DOI: 10.1002/ajh.26960

Language: English

Publisher: Wiley

Publication Date: 2023

detail.hit.zdb_id: 1492749-4

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4953-4953

Abstract: Abstract 4953 Background: Shared decision-making between patients and physicians is broadly advocated in medicine, however little research is available to understand whether this approach would be desirable to all patients regardless of disease type and severity or individual patient characteristics. While clinical decision-making in high-risk myelodysplastic syndromes (MDS) is critical for a number of reasons including: associated comorbidity, symptom burden, and limited life expectancy, no evidence-base data currently exist on patients' preferences. Aim: The objective of this study is twofold: 1) to investigate to what extent high-risk MDS patients prefer to be involved in treatment decision making during consultation just after diagnosis; 2) to identify possible clinical, socio-demographic and patient-reported health status factors associated with patients' preferences for involvement in treatment decisions. Patients and Methods: Data were gathered through an ongoing international prospective observational study involving 15 countries that recruits newly diagnosed patients with intermediate-2 or high-risk IPSS score. All patients were classified according to the WHO histology classification. During the first encounter with their treating physicians, discussing treatment options just after diagnosis, patients were administered a previously internationally validated “control preference scale”. This scale broadly categorizes patients into one of three roles depending on the extent of their preferred involvement in treatment decision-making: “active” (where the patient themselves prefer to decide on which would be the most appropriate treatment option for themselves); “collaborative/shared” (where the patient and the doctor jointly decided on the most appropriate treatment option); “passive” (where the patient prefer to leave decision on the most appropriate treatment option to the doctor). Associations with the following variables were investigated: performance status, comorbidity (“Hematopoietic Cell Transplantation”-“Comorbidity index”), living arrangements, age, gender, education, cultural group, IPSS risk category, evolution from lower IPSS risk scores and patient-reported symptoms (using symptom scales of the EORTC QLQ-C30). Descriptive statistics were used and Mann-Whitney U-test, Kruskall-Wallis test and Fisher's exact test were used as appropriate to test statistical significance of performed comparisons. Results: Study population included overall 121 patients (38% female and 62% male). Mean age of patients was 69 years (min:31.3 max: 87.9) and 80% were diagnosed with IPSS int-2 risk score and 20% with IPSS high risk score. Twenty-six percent evolved from lower IPSS risk scores, while 74% were newly diagnosed with higher-risk. Forty-nine percent favored a passive while only 13% preferred an active role in treatment decision-making; the remaining 38% favored a collaborative/shared decision-making approach. Investigation of factors possibly related to preferred roles, found that passive role was significantly associated with lower education levels (P=.04). Among lower educated patients, 62.5% preferred a passive role compared with only 5% preferring an active role. When investigating relationships with patient-reported symptoms, a general trend for patients preferring a passive role, showing worse outcomes, was also evident. Higher symptom mean scores were found for passive vs. active role groups, being respectively: 46 (sd.26.6) vs. 37 (sd.29.9) for fatigue; 20 (sd.31.8) vs. 2 (sd.8.6) for constipation; 34 (sd.33) vs. 24 (sd.29.5) for dyspnea. Exploratory analysis showed that overall mean symptom score was statistically significant worse in patients preferring a passive role vs. those preferring an active role (P=.01). While other trends of associations were noted, these were not statistically significant. Conclusion: This is the first evidence suggesting that a consistent percentage of high-risk MDS patients prefer a passive role when discussing treatment options with their treating physicians at the time of diagnosis. There is also an indication that these patients are those with lower education levels and presenting with a higher symptom burden. Results need to be confirmed in a larger sample size. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.4953.4953

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e18220-e18220

Abstract: e18220 Background: Whilst a substantial body of knowledge is available on the genetics and biology of MDS, very little is known on quality of life of these patients. We aimed to 1) examine patient-reported symptom prevalence in newly diagnosed MDS patients by disease risk at diagnosis; 2) investigate prevalence of other key symptoms by fatigue severity. Methods: Newly diagnosed MDS patients were recruited in an international prospective observational study from Nov. 2008 to Dec. 2018. As per standard practice, all patients were classified according to the International Prognostic Scoring System (IPSS) that identifies four risk subgroups of patients, i.e. low, intermediate-1 (i.e., lower risk, LR), intermediate-2, and high-risk (i.e., higher risk, HR). At baseline (i.e., pretreatment) patients also completed the validated FACIT-Fatigue scale and the EORTC QLQ-C30 questionnaires. Based on the FACIT-Fatigue median score, two groups were also identified: a lower and a higher fatigue group. Results: Out of 929 patients enrolled, 914 patients were available for current analysis of whom 496 with LR (median age of 74 years) and 418 with HR (median age of 72 years). Prevalence (i.e., with any level of concern) of symptoms by disease risk group is reported in Table. Patients with higher fatigue had a significantly higher prevalence of many other symptoms, such as pain (p 〈 .001), dyspnea (p 〈 .001), insomnia (p 〈 .001), appetite loss (p 〈 .001), diarrhea (p 〈 .001) and constipation (p 〈 .001) than patients with lower fatigue. To illustrate, moderate to severe dyspnea was reported by 38% of patients with higher fatigue and only by 5% of patients who reported lower fatigue. Conclusions: Pretreatment symptom prevalence in newly diagnosed MDS is high, and broadly similar in LR and HR patients. Regardless of disease severity at diagnosis, fatigue is associated with a substantial burden of other symptoms. [Table: see text]

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2019.37.15_suppl.e18220

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2019

detail.hit.zdb_id: 2005181-5