New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients

Haase, Detlef; Germing, Ulrich; Schanz, Julie; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Kündgen, Andrea; Lübbert, Michael; Kunzmann, Regina; Giagounidis, Aristoteles; Aul, Carlo; Trümper, Lorenz; Krieger, O.; Stauder, Reinhard; Müller, Thomas; Wimazal, Friedrich; Valent, Peter; Fonatsch, Christa; Steidl, Christian

doi:10.1182/blood-2007-03-082404

Cited by 710 publications

(754 citation statements)

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“…Interstitial 5q deletions (del(5q)) are the most frequent chromosomal abnormalities in MDS present in 10% to 15% of MDS patients [6][7][8]. The prognosis is favorable with relatively low risk of transformation to AML [9;10] but the dependence on red blood cell (RBC) transfusions often has a negative effect on morbidity and mortality [10].…”

Section: Discussionmentioning

confidence: 99%

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

et al. 2010

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Background: No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no cost study of MDS exists in Germany, the objective of this study was to assess and analyse costs of transfusion-dependent low/intermediate-1 risk MDS in Germany from a payers' perspective. Patients and methods: 116 low/intermediate-1 risk transfusion-dependent MDS patients with and without isolated 5q-deletion from seven centers were identified. Claims data and patient records of the previous five years were used to collect health care utilization data retrospectively. Publicly available tariff books and remuneration schemes were applied to evaluate mean costs per year in Euro with 2007 as base year. Results: The annual cost of MDS patients was estimated at €14,883. Subgroup analyses showed differences in patient's characteristics and outcomes among patients treated at a hospital based versus an office based setting. Patients treated at the hospital based registry show higher cost where as the reasons for that still need to be detected. Overall per annum direct costs range from €12,543 (SD 12,967) to €24,957 (SD 36,399) in different subgroups of patients. In both groups, patients with 5q-deletion use more medication than those without deletion. Mean costs for medication in the office based setting are €5,902 for patients with isolated 5q-deletion vs. €3,932 with no deletion, respectively. Conclusion: MDS leads to a high health care utilization and resulting costs for the health care system which requires a detailed analysis of underlying services.Response to Reviewers: For reasons of a better outline, we decided to respond to your comments in a word document which is attached. Response to reviewer's comments Reviewer's comments ResponsesReviewer #1:In this retrospective study, the authors have evaluated the annual cost of MDS transfused patients in Germany. They stated that patients with 5q-deletion used significantly more resources and especially more medication than those without deletion. This paper raise two majors Criticisms : -1st. The way the data were retrospectively collected raise some issues.In fact the authors compared MDS and del5q but the collection of data were rather different in the two groups and this might also (in part) explain the difference observed in the two groups.Thank you for raising this point. We are aware of this limitation and tried to point it out in the discussion. As this was addressed as a major point by the first reviewer we decided that the respective section needed a revision, which we did in the results and discussion section.To further address this point that was also raised by the editor we conducted additional analyses of the data and present results for the center 7 (MDS registry at a university) separately in a new table 3. By this the differences in data collection and composition of the respective cohorts can be reflected. The fi...

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Section: Discussionmentioning

confidence: 99%

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

et al. 2010

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“…These disorders show substantial clinical variability, ranging from stability for 10 or more years to death due to cytopenias or evolution into acute myeloid leukaemia (AML) within a few months [2]. To more precisely identify patients with markedly different clinical outcomes, over the past 15 years various prognostic scoring systems have been developed and applied [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The International Prognostic Scoring System (IPSS) [8] was that most commonly used and has been now revised [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

“…The International Prognostic Scoring System (IPSS) [8] was that most commonly used and has been now revised [17][18][19]. Thus, cytogenetic abnormalities remain one of the major determinants of MDS pathogenesis, diagnosis, prognosis and guide any potential treatment decisions [12][13][14][15][16][17][18][19][20][21][22][23][24][25], however more sensitive techniques such as array Comparative Genomic Hybridization, Single Nucleotide Polymorphism arrays (SNP-a) and Next-Generation Sequencing are still used in the research setting only [26][27][28][29][30][31]. The IPSS precisely defines the prognostic value of the most frequent chromosomal defects, whereas it does not define rare or combined abnormalities, which are included within the intermediate category [8].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, these latter defects, which flag the extreme cytogenetic heterogeneity of MDS, should be included within a more precise cytogenetic scoring system [21]. In the last 10 years, large patient series have provided some relevant information on rare isolated abnormalities [9][10][11][12][13], but very few have provided information on combined defects [10,13]. In addition, it has become evident that the clinical outcome of patients with a complex karyotype, previously defined by the presence of 3 defects, worsens with an increase in the number of chromosomal defects [13,20,21].…”

Section: Introductionmentioning

confidence: 99%

“…In the last 10 years, large patient series have provided some relevant information on rare isolated abnormalities [9][10][11][12][13], but very few have provided information on combined defects [10,13]. In addition, it has become evident that the clinical outcome of patients with a complex karyotype, previously defined by the presence of 3 defects, worsens with an increase in the number of chromosomal defects [13,20,21]. These limitations have spurred the revision of the IPSS cytogenetic categories and have led to the development of the NCCSS [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

et al. 2013

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This study evaluated whether the NCCSS truly improves the prognostic stratification of 630 consecutive de novo MDS patients and established which cytogenetic grouping [NCCSS or International Prognostic Scoring System (IPSS)], when combined with the WHO classification, best predicted the clinical outcome of myelodysplastic syndromes (MDS). The frequency of chromosomal defects was 53.8%. Clinical parameters, including number of cytopenias, WHO classification, IPSS cytogenetic categories and scores, NCCSS were all relevant for overall survival (OS) and leukemia-free survival (LFS) and were included in six distinct multivariate models compared by the Akaike Information Criterion (AIC). The most effective model to predict OS included the number of cytopenias, the WHO classification and the NCCSS, whereas the model including the number of cytopenias, blast cell percentage and the NCCSS and the model including the number of cytopenias the WHO classification and the NCCSS were almost equally effective to predict LFS. In conclusion, the NCCS (i) improves the prognostic stratification of the good and poor IPSS cytogenetic categories by introducing the very good and the very poor categories; (ii) is still incomplete in establishing the prognostic relevance of rare/double defects, (ii) applied to patients who receive supportive treatment only identifies five different prognostic subgroups, but applied to patients treated with specific therapies reveals only a trend toward a significantly different OS and LFS when patients of the poor and intermediate cytogenetic categories are compared, (iii) combined with the WHO classification is much more effective than the IPSS in predicting MDS clinical outcome. Am. J. Hematol. 88:120-129,

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Targeting Immune Dysregulation in Myelodysplastic Syndromes

Olnes¹

2011

JAMA

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Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis and a tendency to develop leukemia. In some patients, laboratory and clinical evidence supports a role for the immune system in the pathogenesis of early MDS. Many younger patients who respond to immunosuppressive therapy with drugs such as antithymocyte globulin and cyclosporine have clonal expansions of cytotoxic CD8(+) T cells that suppress normal hematopoiesis, as well as expansion of CD4(+) helper T-cell subsets that promote and sustain autoimmunity. Immunosuppressive therapy can produce hematologic responses in some patients and may improve survival and halt leukemic progression. In this report, we describe a 56-year-old woman who presented with fatigue and easy bruising, eventually became pancytopenic, and was diagnosed with MDS. After treatment with a clinical protocol using alemtuzumab, an anti-CD52 antibody, her blood cell counts returned to normal and she has remained in complete remission for more than 2 years of follow-up. In this article, we review the pathobiology of immune dysregulation in MDS and summarize the role of immunosuppressive therapy in MDS.

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New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients

Abstract: We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes

Cited by 710 publications

References 42 publications

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

Targeting Immune Dysregulation in Myelodysplastic Syndromes

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