Skip to main content
Top
Published in: Drugs & Aging 11/2015

01-11-2015 | Therapy in Practice

Myelodysplastic Syndromes in the Elderly: Treatment Options and Personalized Management

Authors: Sonja Burgstaller, Petra Wiesinger, Reinhard Stauder

Published in: Drugs & Aging | Issue 11/2015

Login to get access

Abstract

Myelodysplastic syndromes (MDS) are typical diseases of the elderly, with a median age of 68–75 years at initial diagnosis. Demographic changes producing an increased proportion of elderly in our societies mean the incidence of MDS will rise dramatically. Considering the increasing number of treatment options, ranging from best supportive care to hematopoietic stem cell transplantation (HSCT), decision making is rather complex in this cohort of patients. Moreover, aspects of the aging process also have to be considered in therapy planning. Treatment of elderly MDS patients is dependent on the patient’s individual risk and prognosis. Comorbidities play an essential role as predictors of survival and therapy tolerance. Age-adjusted models and the use of geriatric assessment scores are described as a basis for individualized treatment algorithms. Specific treatment recommendations for the different groups of patients are given. Currently available therapeutic agents, including supportive care, erythropoiesis-stimulating agents (ESAs), immune-modulating agents, hypomethylating agents, and HSCT are described in detail and discussed with a special focus on elderly MDS patients. The inclusion of elderly patients in clinical trials is of utmost importance to obtain data on efficacy and safety in this particular group of patients. Endpoints relevant for the elderly should be integrated, including maintenance of quality of life and functional activities as well as evaluation of use of healthcare resources.
Literature
2.
go back to reference Nösslinger T, Tüchler H, Germing U, Sperr WR, Krieger O, Haase D, Lübbert M, Stauder R, Giagounidis A, Valent P, Pfeilstöcker M. Prognostic impact of age and gender in 897 untreated patients with primary myelodysplastic syndromes. Ann Oncol. 2010;21(1):120–5.PubMedCrossRef Nösslinger T, Tüchler H, Germing U, Sperr WR, Krieger O, Haase D, Lübbert M, Stauder R, Giagounidis A, Valent P, Pfeilstöcker M. Prognostic impact of age and gender in 897 untreated patients with primary myelodysplastic syndromes. Ann Oncol. 2010;21(1):120–5.PubMedCrossRef
3.
go back to reference Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007;109(8):1536–42.PubMedCrossRef Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007;109(8):1536–42.PubMedCrossRef
4.
go back to reference de Swart L, Smith A, Johnston T, Haase D, Droste J, Fenaux P, Symeonidis A, Sanz G, Hellström-Lindberg E, Cermak J, Germing U, Stauder R, Georgescu O, MacKenzie M, Malcovati L, Skov-Holm M, Almeida AM, Mądry K, Slama B, Guerci-Bresler A, Sanhes L, Beyne-Rauzy O, Luno E, Bowen D, De Witte T. Validation of the Revised International Prognostic Scoring System (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukemiaNet MDS (EUMDS) Registry. Br J Haematol. 2015;170(3):372–83.PubMedCrossRef de Swart L, Smith A, Johnston T, Haase D, Droste J, Fenaux P, Symeonidis A, Sanz G, Hellström-Lindberg E, Cermak J, Germing U, Stauder R, Georgescu O, MacKenzie M, Malcovati L, Skov-Holm M, Almeida AM, Mądry K, Slama B, Guerci-Bresler A, Sanhes L, Beyne-Rauzy O, Luno E, Bowen D, De Witte T. Validation of the Revised International Prognostic Scoring System (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukemiaNet MDS (EUMDS) Registry. Br J Haematol. 2015;170(3):372–83.PubMedCrossRef
5.
go back to reference Neukirchen J, Schoonen WM, Strupp C, Gattermann N, Aul C, Haas R, Germing U. Incidence and prevalence of myelodysplastic syndromes: data from the Düsseldorf MDS-registry. Leuk Res. 2011;35(12):1591–6.PubMedCrossRef Neukirchen J, Schoonen WM, Strupp C, Gattermann N, Aul C, Haas R, Germing U. Incidence and prevalence of myelodysplastic syndromes: data from the Düsseldorf MDS-registry. Leuk Res. 2011;35(12):1591–6.PubMedCrossRef
6.
go back to reference Avgerinou C, Alamanos Y, Zikos P, Lampropoulou P, Melachrinou M, Labropoulou V, Tavernarakis I, Aktypi A, Kaiafas P, Raptis C, Kouraklis A, Karakantza M, Symeonidis A. The incidence of myelodysplastic syndromes in Western Greece is increasing. Ann Hematol. 2013;92(7):877–87.PubMedCentralPubMedCrossRef Avgerinou C, Alamanos Y, Zikos P, Lampropoulou P, Melachrinou M, Labropoulou V, Tavernarakis I, Aktypi A, Kaiafas P, Raptis C, Kouraklis A, Karakantza M, Symeonidis A. The incidence of myelodysplastic syndromes in Western Greece is increasing. Ann Hematol. 2013;92(7):877–87.PubMedCentralPubMedCrossRef
7.
go back to reference World Health Organisation. Nutritional anemia: report of a WHO Scientific Group. Geneva: WHO; 1968. World Health Organisation. Nutritional anemia: report of a WHO Scientific Group. Geneva: WHO; 1968.
9.
go back to reference Bach V, Schruckmayer G, Sam I, Kemmler G, Stauder R. Prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large European university hospital cohort. Clin Interv Aging. 2014;9:1187–96.PubMedCentralPubMed Bach V, Schruckmayer G, Sam I, Kemmler G, Stauder R. Prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large European university hospital cohort. Clin Interv Aging. 2014;9:1187–96.PubMedCentralPubMed
10.
go back to reference Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263–8.PubMedCrossRef Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263–8.PubMedCrossRef
11.
go back to reference Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PHM, Newman AB, Cushman M. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165:2214–20.PubMedCrossRef Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PHM, Newman AB, Cushman M. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165:2214–20.PubMedCrossRef
12.
go back to reference Riva E, Tettamanti M, Mosconi P, Apolone G, Gandini F, Nobili A, Tallone MV, Detoma P, Giacomin A, Clerico M, Tempia P, Guala A, Fasolo G, Lucca U. Association of mild anemia with hospitalization and mortality in the elderly: the Health and Anemia population-based study. Haematologica. 2009;94:22–8.PubMedCentralPubMedCrossRef Riva E, Tettamanti M, Mosconi P, Apolone G, Gandini F, Nobili A, Tallone MV, Detoma P, Giacomin A, Clerico M, Tempia P, Guala A, Fasolo G, Lucca U. Association of mild anemia with hospitalization and mortality in the elderly: the Health and Anemia population-based study. Haematologica. 2009;94:22–8.PubMedCentralPubMedCrossRef
13.
go back to reference Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006;119:327–34.PubMedCrossRef Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006;119:327–34.PubMedCrossRef
14.
go back to reference Den Elzen WPJ, Willems JM, Westendorp RGJ, De Craen AJM, Assendelft WJJ, Gussekloo J. Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study. CMAJ. 2009;181:151–7.CrossRef Den Elzen WPJ, Willems JM, Westendorp RGJ, De Craen AJM, Assendelft WJJ, Gussekloo J. Effect of anemia and comorbidity on functional status and mortality in old age: results from the Leiden 85-plus Study. CMAJ. 2009;181:151–7.CrossRef
15.
go back to reference Joosten E, Pelemans W, Hiele M, Noyen J, Verhaeghe R, Boogaerts MA. Prevalence and causes of anaemia in a geriatric hospitalized population. Gerontology. 1992;38:111–7.PubMedCrossRef Joosten E, Pelemans W, Hiele M, Noyen J, Verhaeghe R, Boogaerts MA. Prevalence and causes of anaemia in a geriatric hospitalized population. Gerontology. 1992;38:111–7.PubMedCrossRef
16.
go back to reference Tettamanti M, Lucca U, Gandini F, Recchia A, Mosconi P, Apolone G, Nobili A, Tallone MV, Detoma P, Giacomin A, Clerico M, Tempia P, Savoia L, Fasolo G, Ponchio L, Della Porta MG, Riva E. Prevalence, incidence and types of mild anemia in the elderly: the ‘Health and Anemia’ population-based study. Haematologica. 2010;95:1849–56.PubMedCentralPubMedCrossRef Tettamanti M, Lucca U, Gandini F, Recchia A, Mosconi P, Apolone G, Nobili A, Tallone MV, Detoma P, Giacomin A, Clerico M, Tempia P, Savoia L, Fasolo G, Ponchio L, Della Porta MG, Riva E. Prevalence, incidence and types of mild anemia in the elderly: the ‘Health and Anemia’ population-based study. Haematologica. 2010;95:1849–56.PubMedCentralPubMedCrossRef
17.
go back to reference Hui P, Cook DJ, Lim W, Fraser GA, Arnold DM. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest. 2011;139:271–8.PubMedCrossRef Hui P, Cook DJ, Lim W, Fraser GA, Arnold DM. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest. 2011;139:271–8.PubMedCrossRef
18.
go back to reference Neukirchen J, Blum S, Kuendgen A, Strupp C, Aivado M, Haas R, Aul C, Gattermann N, Germing U. Platelet counts and haemorrhagic diathesis in patients with myelodysplastic syndromes. Eur J Haematol. 2009;83(5):477–82.PubMedCrossRef Neukirchen J, Blum S, Kuendgen A, Strupp C, Aivado M, Haas R, Aul C, Gattermann N, Germing U. Platelet counts and haemorrhagic diathesis in patients with myelodysplastic syndromes. Eur J Haematol. 2009;83(5):477–82.PubMedCrossRef
19.
go back to reference Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the US population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486–92.PubMedCrossRef Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the US population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486–92.PubMedCrossRef
20.
go back to reference Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, Wierda WG, Pierce S, Estey E, Liu J, Huang X, Kantarjian H. A prognostic score for patients with lower risk myelodysplastic syndrome. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2008;22:538–43.CrossRef Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, Wierda WG, Pierce S, Estey E, Liu J, Huang X, Kantarjian H. A prognostic score for patients with lower risk myelodysplastic syndrome. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2008;22:538–43.CrossRef
21.
go back to reference Goldberg SL, Chen E, Corral M, Guo A, Mody-Patel N, Pecora AL, Laouri M. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol. 2010;28:2847–52.PubMedCrossRef Goldberg SL, Chen E, Corral M, Guo A, Mody-Patel N, Pecora AL, Laouri M. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol. 2010;28:2847–52.PubMedCrossRef
22.
go back to reference Malcovati L, Hellström-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, Della Porta MG, Fenaux P, Gattermann N, Germing U, Jansen JH, Mittelman M, Mufti G, Platzbecker U, Sanz GF, Selleslag D, Skov-Holm M, Stauder R, Symeonidis A, Van De Loosdrecht AA, De Witte T, Cazzola M. Diagnosis and treatment of primary myelodysplastic syndromes in adults: Recommendations from the European LeukemiaNet. Blood. 2013;122:2943–64.PubMedCentralPubMedCrossRef Malcovati L, Hellström-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, Della Porta MG, Fenaux P, Gattermann N, Germing U, Jansen JH, Mittelman M, Mufti G, Platzbecker U, Sanz GF, Selleslag D, Skov-Holm M, Stauder R, Symeonidis A, Van De Loosdrecht AA, De Witte T, Cazzola M. Diagnosis and treatment of primary myelodysplastic syndromes in adults: Recommendations from the European LeukemiaNet. Blood. 2013;122:2943–64.PubMedCentralPubMedCrossRef
23.
go back to reference Haase D, Germing U, Schanz J, Pfeilstöcker M, Nösslinger T, Hildebrandt B, Kundgen A, Lübbert M, Kunzmann R, Giagounidis AAN, Aul C, Trümper L, Krieger O, Stauder R, Müller TH, Wimazal F, Valent P, Fonatsch C, Steidl C. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110:4385–95.PubMedCrossRef Haase D, Germing U, Schanz J, Pfeilstöcker M, Nösslinger T, Hildebrandt B, Kundgen A, Lübbert M, Kunzmann R, Giagounidis AAN, Aul C, Trümper L, Krieger O, Stauder R, Müller TH, Wimazal F, Valent P, Fonatsch C, Steidl C. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110:4385–95.PubMedCrossRef
24.
go back to reference Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, Van De Loosdrecht AA, Germing U, Haase D. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.PubMedCentralPubMedCrossRef Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, Van De Loosdrecht AA, Germing U, Haase D. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.PubMedCentralPubMedCrossRef
25.
go back to reference Porta MGD, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstöcker M, Sekeres MA, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D, Greenberg PL, Cazzola M. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodyspla. Leukemia. 2015;29(7):1502–13.PubMedCrossRef Porta MGD, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstöcker M, Sekeres MA, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D, Greenberg PL, Cazzola M. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodyspla. Leukemia. 2015;29(7):1502–13.PubMedCrossRef
26.
go back to reference Braulke F, Platzbecker U, Muller-Thomas C, Gotze K, Germing U, Brummendorf TH, Nolte F, Hofmann W-K, Giagounidis AAN, Lubbert M, Greenberg PL, Bennett JM, Sole F, Mallo M, Slovak ML, Ohyashiki K, Le Beau MM, Tuchler H, Pfeilstocker M, Nosslinger T, Hildebrandt B, Shirneshan K, Aul C, Stauder R, Sperr WR, Valent P, Fonatsch C, Trumper L, Haase D, Schanz J. Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+ FISH: results from a German diagnostic study in comparison with an international control group. Haematologica. 2015;100(2):205–13.PubMedCrossRef Braulke F, Platzbecker U, Muller-Thomas C, Gotze K, Germing U, Brummendorf TH, Nolte F, Hofmann W-K, Giagounidis AAN, Lubbert M, Greenberg PL, Bennett JM, Sole F, Mallo M, Slovak ML, Ohyashiki K, Le Beau MM, Tuchler H, Pfeilstocker M, Nosslinger T, Hildebrandt B, Shirneshan K, Aul C, Stauder R, Sperr WR, Valent P, Fonatsch C, Trumper L, Haase D, Schanz J. Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+ FISH: results from a German diagnostic study in comparison with an international control group. Haematologica. 2015;100(2):205–13.PubMedCrossRef
27.
go back to reference Van De Loosdrecht AA, Westers TM, Westra AH, Dräger AM, Van Der Velden VHJ, Ossenkoppele GJ. Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood. 2008;111(3):1067–77.PubMedCrossRef Van De Loosdrecht AA, Westers TM, Westra AH, Dräger AM, Van Der Velden VHJ, Ossenkoppele GJ. Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood. 2008;111(3):1067–77.PubMedCrossRef
28.
go back to reference Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb HJ, Krieger O, Loken M, van de Loosdrecht A, Ogata K, Orfao A, Pfeilstöcker M, Rüter B, Sperr WR, Stauder R, Wells DA. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31(6):727–36.PubMedCrossRef Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb HJ, Krieger O, Loken M, van de Loosdrecht A, Ogata K, Orfao A, Pfeilstöcker M, Rüter B, Sperr WR, Stauder R, Wells DA. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31(6):727–36.PubMedCrossRef
29.
go back to reference Bruning RD, Orazi A, Germing U, Le Beau MM, Porwit A, Baumann I. Myelodysplastic syndromes. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. World Health Organization classification of tumours of the hematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008. Bruning RD, Orazi A, Germing U, Le Beau MM, Porwit A, Baumann I. Myelodysplastic syndromes. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. World Health Organization classification of tumours of the hematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2008.
30.
go back to reference Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMed Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMed
31.
go back to reference Schanz J, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Tuechler H, Valent P, Hildebrandt B, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Kantarjian H, Germing U, Haase D, Estey E. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the International Prognostic Scoring System. J Clin Oncol. 2011;29(15):1963–70.PubMedCrossRef Schanz J, Steidl C, Fonatsch C, Pfeilstöcker M, Nösslinger T, Tuechler H, Valent P, Hildebrandt B, Giagounidis A, Aul C, Lübbert M, Stauder R, Krieger O, Garcia-Manero G, Kantarjian H, Germing U, Haase D, Estey E. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the International Prognostic Scoring System. J Clin Oncol. 2011;29(15):1963–70.PubMedCrossRef
32.
go back to reference Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, Giagounidis A, Hildebrandt B, Bernasconi P, Knipp S, Strupp C, Lazzarino M, Aul C, Cazzola M. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10.PubMedCrossRef Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, Giagounidis A, Hildebrandt B, Bernasconi P, Knipp S, Strupp C, Lazzarino M, Aul C, Cazzola M. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10.PubMedCrossRef
33.
go back to reference Malcovati L, DellaPorta MG, Strupp C, Ambaglio I, Kuendgen A, Nachtkamp K, Travaglino E, Invernizzi R, Pascutto C, Lazzarino M, Germing U, Cazzola M. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based prognostic scoring system (WPSS). Haematologica. 2011;96(10):1433–40.PubMedCentralPubMedCrossRef Malcovati L, DellaPorta MG, Strupp C, Ambaglio I, Kuendgen A, Nachtkamp K, Travaglino E, Invernizzi R, Pascutto C, Lazzarino M, Germing U, Cazzola M. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based prognostic scoring system (WPSS). Haematologica. 2011;96(10):1433–40.PubMedCentralPubMedCrossRef
34.
go back to reference Walter LC, Covinsky KE. Cancer screening in elderly patients: a framework for individualized decision making. JAMA. 2001;285(21):2750–6.PubMedCrossRef Walter LC, Covinsky KE. Cancer screening in elderly patients: a framework for individualized decision making. JAMA. 2001;285(21):2750–6.PubMedCrossRef
35.
go back to reference Bammer C, Sperr WR, Kemmler G, Wimazal F, Nösslinger T, Schönmetzler A, Krieger O, Pfeilstöcker M, Valent P, Stauder R. Clustering of comorbidities is related to age and sex and impacts clinical outcome in myelodysplastic syndromes. J Geriatr Oncol. 2014;5(3):299–306.PubMedCrossRef Bammer C, Sperr WR, Kemmler G, Wimazal F, Nösslinger T, Schönmetzler A, Krieger O, Pfeilstöcker M, Valent P, Stauder R. Clustering of comorbidities is related to age and sex and impacts clinical outcome in myelodysplastic syndromes. J Geriatr Oncol. 2014;5(3):299–306.PubMedCrossRef
36.
go back to reference Sperr WR, Wimazal F, Kundi M, Baumgartner C, Nösslinger T, Makrai A, Stauder R, Krieger O, Pfeilstöcker M, Valent P. Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS study group. Ann Oncol. 2009;21(1):114–9.PubMedCrossRef Sperr WR, Wimazal F, Kundi M, Baumgartner C, Nösslinger T, Makrai A, Stauder R, Krieger O, Pfeilstöcker M, Valent P. Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS study group. Ann Oncol. 2009;21(1):114–9.PubMedCrossRef
37.
go back to reference Stauder R, Nösslinger T, Pfeilstöcker M, Sperr WR, Wimazal F, Krieger O, Valent P. Impact of age and comorbidity in Myelodysplastic syndromes. JNCCN J Natl Compr Cancer Netw. 2008;6(9):927–34. Stauder R, Nösslinger T, Pfeilstöcker M, Sperr WR, Wimazal F, Krieger O, Valent P. Impact of age and comorbidity in Myelodysplastic syndromes. JNCCN J Natl Compr Cancer Netw. 2008;6(9):927–34.
38.
go back to reference Naqvi K, Garcia-Manero G, Sardesai S, Oh J, Vigil CE, Pierce S, Lei X, Shan J, Kantarjian HM, Suarez-Almazor ME. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J Clin Oncol. 2011;29(16):2240–6.PubMedCentralPubMedCrossRef Naqvi K, Garcia-Manero G, Sardesai S, Oh J, Vigil CE, Pierce S, Lei X, Shan J, Kantarjian HM, Suarez-Almazor ME. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J Clin Oncol. 2011;29(16):2240–6.PubMedCentralPubMedCrossRef
39.
go back to reference Sperr WR, Kundi M, Wimazal F, Nosslinger T, Schonmetzler-Makrai A, Stauder R, Krieger O, Neukirchen J, Germing U, Pfeilstocker M, Valent P. Proposed score for survival of patients with myelodysplastic syndromes. Eur J Clin Invest. 2013;43(11):1120–8.PubMed Sperr WR, Kundi M, Wimazal F, Nosslinger T, Schonmetzler-Makrai A, Stauder R, Krieger O, Neukirchen J, Germing U, Pfeilstocker M, Valent P. Proposed score for survival of patients with myelodysplastic syndromes. Eur J Clin Invest. 2013;43(11):1120–8.PubMed
40.
go back to reference Della Porta MG, Malcovati L, Strupp C, Ambaglio I, Kuendgen A, Zipperer E, Travaglino E, Invernizzi R, Pascutto C, Lazzarino M, Germing U, Cazzola M. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica. 2011;96(3):441–9.PubMedCentralPubMedCrossRef Della Porta MG, Malcovati L, Strupp C, Ambaglio I, Kuendgen A, Zipperer E, Travaglino E, Invernizzi R, Pascutto C, Lazzarino M, Germing U, Cazzola M. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica. 2011;96(3):441–9.PubMedCentralPubMedCrossRef
41.
go back to reference Breccia M, Federico V, Latagliata R, Mercanti C, D’Elia GM, Cannella L, Loglisci G, Salaroli A, Santopietro M, Alimena G. Evaluation of comorbidities at diagnosis predicts outcome in myelodysplastic syndrome patients. Leuk Res. 2011;35(2):159–62.PubMedCrossRef Breccia M, Federico V, Latagliata R, Mercanti C, D’Elia GM, Cannella L, Loglisci G, Salaroli A, Santopietro M, Alimena G. Evaluation of comorbidities at diagnosis predicts outcome in myelodysplastic syndrome patients. Leuk Res. 2011;35(2):159–62.PubMedCrossRef
42.
go back to reference Wang R, Gross CP, Halene S, Ma X. Comorbidities and survival in a large cohort of patients with newly diagnosed myelodysplastic syndromes. Leuk Res. 2009;33(12):1594–8.PubMedCentralPubMedCrossRef Wang R, Gross CP, Halene S, Ma X. Comorbidities and survival in a large cohort of patients with newly diagnosed myelodysplastic syndromes. Leuk Res. 2009;33(12):1594–8.PubMedCentralPubMedCrossRef
43.
go back to reference Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61–5.PubMed Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61–5.PubMed
44.
go back to reference Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–86.PubMedCrossRef Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–86.PubMedCrossRef
45.
go back to reference Podsiadlo D, Richardson S. The timed ‘Up & Go’: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–8.PubMedCrossRef Podsiadlo D, Richardson S. The timed ‘Up & Go’: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–8.PubMedCrossRef
46.
go back to reference Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.PubMedCrossRef Folstein MF, Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.PubMedCrossRef
47.
go back to reference Guigoz Y, Vellas BJ. Malnutrition in the elderly: the Mini Nutritional Assessment (MNA). Ther Umsch. 1997;54(6):345–50.PubMed Guigoz Y, Vellas BJ. Malnutrition in the elderly: the Mini Nutritional Assessment (MNA). Ther Umsch. 1997;54(6):345–50.PubMed
48.
go back to reference Bellera CA, Rainfray M, Mathoulin-Pélissier S, Mertens C, Delva F, Fonck M, Soubeyran PL. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol. 2012;23(8):2166–72.PubMedCrossRef Bellera CA, Rainfray M, Mathoulin-Pélissier S, Mertens C, Delva F, Fonck M, Soubeyran PL. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol. 2012;23(8):2166–72.PubMedCrossRef
49.
go back to reference Hamaker ME, Mitrovic M, Stauder R. The G8 screening tool detects relevant geriatric impairments and predicts survival in elderly patients with a haematological malignancy. Ann Hematol. 2014;93(6):1031–40.PubMedCrossRef Hamaker ME, Mitrovic M, Stauder R. The G8 screening tool detects relevant geriatric impairments and predicts survival in elderly patients with a haematological malignancy. Ann Hematol. 2014;93(6):1031–40.PubMedCrossRef
50.
go back to reference Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy—a systematic review. Leuk Res. 2014;38(3):275–83.PubMedCrossRef Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy—a systematic review. Leuk Res. 2014;38(3):275–83.PubMedCrossRef
51.
go back to reference Deschler B, Ihorst G, Platzbecker U, Germing U, März E, De Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lübbert M. 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. Haematologica. 2013;98(2):208–16.PubMedCentralPubMedCrossRef Deschler B, Ihorst G, Platzbecker U, Germing U, März E, De Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lübbert M. 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. Haematologica. 2013;98(2):208–16.PubMedCentralPubMedCrossRef
52.
go back to reference Wildes TM, Ruwe AP, Fournier C, Gao F, Carson KR, Piccirillo JF, Tan B, Colditz GA. Geriatric assessment is associated with completion of chemotherapy, toxicity, and survival in older adults with cancer. J Geriatr Oncol. 2013;4(3):227–34.PubMedCentralPubMedCrossRef Wildes TM, Ruwe AP, Fournier C, Gao F, Carson KR, Piccirillo JF, Tan B, Colditz GA. Geriatric assessment is associated with completion of chemotherapy, toxicity, and survival in older adults with cancer. J Geriatr Oncol. 2013;4(3):227–34.PubMedCentralPubMedCrossRef
53.
go back to reference Klepin HD, Rao AV, Pardee TS. Acute myeloid leukemia and myelodysplastic syndromes in older adults. J Clin Oncol. 2014;32(24):2541–52.PubMedCrossRef Klepin HD, Rao AV, Pardee TS. Acute myeloid leukemia and myelodysplastic syndromes in older adults. J Clin Oncol. 2014;32(24):2541–52.PubMedCrossRef
54.
go back to reference Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5(3):224–37.PubMedCrossRef Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5(3):224–37.PubMedCrossRef
55.
go back to reference Stauder R. The challenge of individualised risk assessment and therapy planning in elderly high-risk myelodysplastic syndromes (MDS) patients. Ann Hematol. 2012;91(9):1333–43.PubMedCentralPubMedCrossRef Stauder R. The challenge of individualised risk assessment and therapy planning in elderly high-risk myelodysplastic syndromes (MDS) patients. Ann Hematol. 2012;91(9):1333–43.PubMedCentralPubMedCrossRef
56.
go back to reference Efficace F, Gaidano G, Breccia M, Criscuolo M, Cottone F, Caocci G, Bowen D, Lübbert M, Angelucci E, Stauder R, Selleslag D, Platzbecker U, Sanpaolo G, Jonasova A, Buccisano F, Specchia G, Palumbo GA, Niscola P, Wan C, Zhang H, Fenu S, Klimek V, Beyne-Rauzy O, Nguyen K, Mandelli F. Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes. Br J Haematol. 2015;168(3):361–70.PubMedCrossRef Efficace F, Gaidano G, Breccia M, Criscuolo M, Cottone F, Caocci G, Bowen D, Lübbert M, Angelucci E, Stauder R, Selleslag D, Platzbecker U, Sanpaolo G, Jonasova A, Buccisano F, Specchia G, Palumbo GA, Niscola P, Wan C, Zhang H, Fenu S, Klimek V, Beyne-Rauzy O, Nguyen K, Mandelli F. Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes. Br J Haematol. 2015;168(3):361–70.PubMedCrossRef
57.
go back to reference Hamaker ME, Stauder R, van Munster BC. On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points? Ann Oncol. 2014;25(3):675–81.PubMedCentralPubMedCrossRef Hamaker ME, Stauder R, van Munster BC. On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points? Ann Oncol. 2014;25(3):675–81.PubMedCentralPubMedCrossRef
58.
59.
go back to reference Fenaux P, Hasse D, Sanz GF, Santini V, Buske C. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57–69.PubMedCrossRef Fenaux P, Hasse D, Sanz GF, Santini V, Buske C. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii57–69.PubMedCrossRef
60.
go back to reference Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A, Mueller BU, O’Brien SH, Pasquini M, Sarode R, Solberg L, Haynes AE, Crowther MA. The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. Hematol Am Soc Hematol Educ Program. 2013;2013:9–14.CrossRef Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A, Mueller BU, O’Brien SH, Pasquini M, Sarode R, Solberg L, Haynes AE, Crowther MA. The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. Hematol Am Soc Hematol Educ Program. 2013;2013:9–14.CrossRef
61.
go back to reference Jensen PD, Jensen FT, Christensen T, Eiskjær H, Baandrup U, Nielsen JL. Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. Blood. 2003;101(11):4632–9.PubMedCrossRef Jensen PD, Jensen FT, Christensen T, Eiskjær H, Baandrup U, Nielsen JL. Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. Blood. 2003;101(11):4632–9.PubMedCrossRef
62.
go back to reference Rose C, Brechignac S, Vassilief D, Pascal L, Stamatoullas A, Guerci A, Larbaa D, Dreyfus F, Beyne-Rauzy O, Chaury MP, Roy L, Cheze S, Morel P, Fenaux P. Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM (Groupe Francophone des Myélodysplasies). Leuk Res. 2010;34(7):864–70.PubMedCrossRef Rose C, Brechignac S, Vassilief D, Pascal L, Stamatoullas A, Guerci A, Larbaa D, Dreyfus F, Beyne-Rauzy O, Chaury MP, Roy L, Cheze S, Morel P, Fenaux P. Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM (Groupe Francophone des Myélodysplasies). Leuk Res. 2010;34(7):864–70.PubMedCrossRef
63.
go back to reference Breccia M, Voso MT, Aloe Spiriti MA, Fenu S, Maurillo L, Buccisano F, Tafuri A, Alimena G. An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms. Ann Haematol. 2015;94(5):771–7.CrossRef Breccia M, Voso MT, Aloe Spiriti MA, Fenu S, Maurillo L, Buccisano F, Tafuri A, Alimena G. An increase in hemoglobin, platelets and white blood cells levels by iron chelation as single treatment in multitransfused patients with myelodysplastic syndromes: clinical evidences and possible biological mechanisms. Ann Haematol. 2015;94(5):771–7.CrossRef
64.
go back to reference Valent P, Krieger O, Stauder R, Wimazal F, Nösslinger T, Sperr WR, Sill H, Bettelheim P, Pfeilstöcker M. Iron overload in myelodysplastic syndromes (MDS)—diagnosis, management, and response criteria: a proposal of the Austrian MDS platform. Eur J Clin Invest. 2008;38(3):143–9.PubMedCentralPubMedCrossRef Valent P, Krieger O, Stauder R, Wimazal F, Nösslinger T, Sperr WR, Sill H, Bettelheim P, Pfeilstöcker M. Iron overload in myelodysplastic syndromes (MDS)—diagnosis, management, and response criteria: a proposal of the Austrian MDS platform. Eur J Clin Invest. 2008;38(3):143–9.PubMedCentralPubMedCrossRef
65.
go back to reference Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, Soiffer RJ, Antin JH. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109(10):4586–8.PubMedCentralPubMedCrossRef Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, Soiffer RJ, Antin JH. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007;109(10):4586–8.PubMedCentralPubMedCrossRef
66.
go back to reference List AF, Baer MR, Steensma DP, Raza A, Esposito J, Martinez-Lopez N, Paley C, Feigert J, Besa E. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012;30(17):2134–9.PubMedCrossRef List AF, Baer MR, Steensma DP, Raza A, Esposito J, Martinez-Lopez N, Paley C, Feigert J, Besa E. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012;30(17):2134–9.PubMedCrossRef
67.
go back to reference Ross SD, Allen IE, Probst CA, Sercus B, Crean SM, Ranganathan G. Efficacy and safety of erythropoiesis-stimulating proteins in myelodysplastic syndrome: a systematic review and meta-analysis. Oncologist. 2007;12(10):1264–73.PubMedCrossRef Ross SD, Allen IE, Probst CA, Sercus B, Crean SM, Ranganathan G. Efficacy and safety of erythropoiesis-stimulating proteins in myelodysplastic syndrome: a systematic review and meta-analysis. Oncologist. 2007;12(10):1264–73.PubMedCrossRef
68.
go back to reference Mundle S, Lefebvre P, Vekeman F, Duh MS, Rastogi R, Moyo V. An assessment of erythroid response to epoetin α as a single agent versus in combination with granulocyte- or granulocyte- macrophage-colony-stimulating factor in myelodysplastic syndromes using a meta-analysis approach. Cancer. 2009;115(4):706–15.PubMedCrossRef Mundle S, Lefebvre P, Vekeman F, Duh MS, Rastogi R, Moyo V. An assessment of erythroid response to epoetin α as a single agent versus in combination with granulocyte- or granulocyte- macrophage-colony-stimulating factor in myelodysplastic syndromes using a meta-analysis approach. Cancer. 2009;115(4):706–15.PubMedCrossRef
69.
go back to reference Moyo V, Lefebvre P, Duh MS, Yektashenas B, Mundle S. Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis. Ann Hematol. 2008;87(7):527–36.PubMedCrossRef Moyo V, Lefebvre P, Duh MS, Yektashenas B, Mundle S. Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis. Ann Hematol. 2008;87(7):527–36.PubMedCrossRef
70.
go back to reference Garcia-Manero G. Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014;89(1):97–108.PubMedCrossRef Garcia-Manero G. Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014;89(1):97–108.PubMedCrossRef
71.
go back to reference Hellström-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, Ost A, Greenberg P. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol. 1997;99(2):344–51.PubMedCrossRef Hellström-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, Ost A, Greenberg P. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol. 1997;99(2):344–51.PubMedCrossRef
72.
go back to reference Hellström-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IMS, Dybedal I, Grimfors G, Hesse-Sundin E, Hjorth M, Kanter-Lewensohn L, Linder O, Luthman M, Löfvenberg E, Öberg G, Porwit-MacDonald A, Rådlund A, Samuelsson J, Tangen JM, Winquist I, Wisloff F. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120(6):1037–46.PubMedCrossRef Hellström-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IMS, Dybedal I, Grimfors G, Hesse-Sundin E, Hjorth M, Kanter-Lewensohn L, Linder O, Luthman M, Löfvenberg E, Öberg G, Porwit-MacDonald A, Rådlund A, Samuelsson J, Tangen JM, Winquist I, Wisloff F. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120(6):1037–46.PubMedCrossRef
73.
go back to reference Gonzalez-Porras JR, Cordoba I, Such E, Nomdedeu B, Vallespi T, Carbonell F, Luño E, Ardanaz M, Ramos F, Pedro C, Gomez V, De Paz R, Sanchez-Barba M, Sanz GF, Del Cañizo C. Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome. Cancer. 2011;117(24):5529–37.PubMedCrossRef Gonzalez-Porras JR, Cordoba I, Such E, Nomdedeu B, Vallespi T, Carbonell F, Luño E, Ardanaz M, Ramos F, Pedro C, Gomez V, De Paz R, Sanchez-Barba M, Sanz GF, Del Cañizo C. Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome. Cancer. 2011;117(24):5529–37.PubMedCrossRef
74.
go back to reference Stolla M, Refaai MA, Heal JM, Spinelli SL, Garraud O, Phipps RP, Blumberg N. Platelet transfusion—the new immunology of an old therapy. Front Immunol. 2015;6:28.PubMedCentralPubMedCrossRef Stolla M, Refaai MA, Heal JM, Spinelli SL, Garraud O, Phipps RP, Blumberg N. Platelet transfusion—the new immunology of an old therapy. Front Immunol. 2015;6:28.PubMedCentralPubMedCrossRef
75.
go back to reference Brierley CK, Steensma DP. Thrombopoiesis-stimulating agents and myelodysplastic syndromes. Br J Haematol. 2015;169(3):309–23.PubMedCrossRef Brierley CK, Steensma DP. Thrombopoiesis-stimulating agents and myelodysplastic syndromes. Br J Haematol. 2015;169(3):309–23.PubMedCrossRef
76.
go back to reference Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, Garcia-Manero G, Hu K, Franklin JL, Berger DP. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010;116(17):3163–70.PubMedCentralPubMedCrossRef Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, Garcia-Manero G, Hu K, Franklin JL, Berger DP. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010;116(17):3163–70.PubMedCentralPubMedCrossRef
77.
go back to reference Kantarjian H, Fenaux P, Sekeres MA, Becker PS, Boruchov A, Bowen D, Hellstrom-Lindberg E, Larson RA, Lyons RM, Muus P, Shammo J, Siegel R, Hu K, Franklin J, Berger DP. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol. 2010;28(3):437–44.PubMedCrossRef Kantarjian H, Fenaux P, Sekeres MA, Becker PS, Boruchov A, Bowen D, Hellstrom-Lindberg E, Larson RA, Lyons RM, Muus P, Shammo J, Siegel R, Hu K, Franklin J, Berger DP. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol. 2010;28(3):437–44.PubMedCrossRef
78.
go back to reference Oliva EN, Santini V, Zini G, Palumbo GA, Poloni A, Cortelezzi A, Voso MT, Molteni A, Sanpaolo G, Marino A, Rodà F, Alati C, Ronco F, Di Raimondo F, Leoni P, Alimena G, Finotto S, Latagliata R, Nobile F. Efficacy and safety of eltrombopag for the treatment of thrombocytopenia of low and intermediate-1 IPSS risk myelodysplastic syndromes: interim analysis of a prospective, randomized, single-blind, placebo-controlled trial (EQoL-MDS). Blood. 2012;120:20.CrossRef Oliva EN, Santini V, Zini G, Palumbo GA, Poloni A, Cortelezzi A, Voso MT, Molteni A, Sanpaolo G, Marino A, Rodà F, Alati C, Ronco F, Di Raimondo F, Leoni P, Alimena G, Finotto S, Latagliata R, Nobile F. Efficacy and safety of eltrombopag for the treatment of thrombocytopenia of low and intermediate-1 IPSS risk myelodysplastic syndromes: interim analysis of a prospective, randomized, single-blind, placebo-controlled trial (EQoL-MDS). Blood. 2012;120:20.CrossRef
79.
go back to reference Giagounidis A, Mufti GJ, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, Gaidano G, Wiktor-Jedrzejczak W, Hu K, Woodard P, Yang AS, Kantarjian HM. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer. 2014;120(12):1838–46.PubMedCentralPubMedCrossRef Giagounidis A, Mufti GJ, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, Gaidano G, Wiktor-Jedrzejczak W, Hu K, Woodard P, Yang AS, Kantarjian HM. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer. 2014;120(12):1838–46.PubMedCentralPubMedCrossRef
80.
go back to reference Kalota A, Selak MA, Garcia-Cid LA, Carroll M. Eltrombopag modulates reactive oxygen species and decreases acute myeloid leukemia cell survival. PLoS One. 2015;10(4):e0126691.PubMedCentralPubMedCrossRef Kalota A, Selak MA, Garcia-Cid LA, Carroll M. Eltrombopag modulates reactive oxygen species and decreases acute myeloid leukemia cell survival. PLoS One. 2015;10(4):e0126691.PubMedCentralPubMedCrossRef
81.
go back to reference Kelaidi C, Park S, Brechignac S, Mannone L, Vey N, Dombret H, Aljassem L, Stamatoullas A, Adès L, Giraudier S, de Botton S, Raynaud S, Lepelley P, Picard F, Leroux G, Daniel MT, Bouscary D, Dreyfus F, Fenaux P. Treatment of myelodysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide. Leuk Res. 2008;32(7):1049–53.PubMedCrossRef Kelaidi C, Park S, Brechignac S, Mannone L, Vey N, Dombret H, Aljassem L, Stamatoullas A, Adès L, Giraudier S, de Botton S, Raynaud S, Lepelley P, Picard F, Leroux G, Daniel MT, Bouscary D, Dreyfus F, Fenaux P. Treatment of myelodysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide. Leuk Res. 2008;32(7):1049–53.PubMedCrossRef
82.
go back to reference List AF, Bennett JM, Sekeres MA, Skikne B, Fu T, Shammo JM, Nimer SD, Knight RD, Giagounidis A. Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS. Leukemia. 2014;28(5):1033–40.PubMedCentralPubMedCrossRef List AF, Bennett JM, Sekeres MA, Skikne B, Fu T, Shammo JM, Nimer SD, Knight RD, Giagounidis A. Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS. Leukemia. 2014;28(5):1033–40.PubMedCentralPubMedCrossRef
83.
go back to reference Jädersten M, Saft L, Smith A, Kulasekararaj A, Pomplun S, Göhring G, Hedlund A, Hast R, Schlegelberger B, Porwit A, Hellström-Lindberg E, Mufti GJ. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 2011;29(15):1971–9.PubMedCrossRef Jädersten M, Saft L, Smith A, Kulasekararaj A, Pomplun S, Göhring G, Hedlund A, Hast R, Schlegelberger B, Porwit A, Hellström-Lindberg E, Mufti GJ. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 2011;29(15):1971–9.PubMedCrossRef
84.
go back to reference Syed YY, Scott LJ. Lenalidomide: a review of its use in patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndrome associated with 5q chromosome deletion. Drugs. 2013;73(11):1183–96.PubMedCrossRef Syed YY, Scott LJ. Lenalidomide: a review of its use in patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndrome associated with 5q chromosome deletion. Drugs. 2013;73(11):1183–96.PubMedCrossRef
85.
go back to reference Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, Muus P, Te Boekhorst P, Sanz G, Del Cañizo C, Guerci-Bresler A, Nilsson L, Platzbecker U, Lübbert M, Quesnel B, Cazzola M, Ganser A, Bowen D, Schlegelberger B, Aul C, Knight R, Francis J, Fu T, Hellström-Lindberg E. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118(14):3765–76.PubMedCrossRef Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, Muus P, Te Boekhorst P, Sanz G, Del Cañizo C, Guerci-Bresler A, Nilsson L, Platzbecker U, Lübbert M, Quesnel B, Cazzola M, Ganser A, Bowen D, Schlegelberger B, Aul C, Knight R, Francis J, Fu T, Hellström-Lindberg E. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118(14):3765–76.PubMedCrossRef
86.
go back to reference Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, Dreisbach L, Schiffer CA, Stone RM, Greenberg PL, Curtin PT, Klimek VM, Shammo JM, Thomas D, Knight RD, Schmidt M, Wride K, Zeldis JB, List AF. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111(1):86–93.PubMedCrossRef Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, Dreisbach L, Schiffer CA, Stone RM, Greenberg PL, Curtin PT, Klimek VM, Shammo JM, Thomas D, Knight RD, Schmidt M, Wride K, Zeldis JB, List AF. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111(1):86–93.PubMedCrossRef
87.
go back to reference Abou Zahr A, Saad Aldin E, Komrokji R, Zeidan A. Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes. J Blood Med. 2014;6:1.PubMedCentralPubMed Abou Zahr A, Saad Aldin E, Komrokji R, Zeidan A. Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes. J Blood Med. 2014;6:1.PubMedCentralPubMed
88.
go back to reference Santini V, Almeida AM, Giagounidis A, Gröpper S, Jonasova A, Vey N, Mufti GJ, Buckstein R, Mittelman M, Platzbecker U, Shpilberg O, Ram R, Del Cañizo C, Gattermann N, Ozawa K, Zhong J, Séguy F, Hoenekopp A, Beach CL, Fenaux P. Paper: efficacy and safety of lenalidomide (LEN) versus placebo (PBO) in RBC-transfusion dependent (TD) patients (Pts) with IPSS low/intermediate (int-1)-risk myelodysplastic syndromes (MDS) without Del(5q) and unresponsive or refractory to erythropoiesis. https://ash.confex.com/ash/2014/webprogram/Paper70494.html. Accessed 13 April 2015. Santini V, Almeida AM, Giagounidis A, Gröpper S, Jonasova A, Vey N, Mufti GJ, Buckstein R, Mittelman M, Platzbecker U, Shpilberg O, Ram R, Del Cañizo C, Gattermann N, Ozawa K, Zhong J, Séguy F, Hoenekopp A, Beach CL, Fenaux P. Paper: efficacy and safety of lenalidomide (LEN) versus placebo (PBO) in RBC-transfusion dependent (TD) patients (Pts) with IPSS low/intermediate (int-1)-risk myelodysplastic syndromes (MDS) without Del(5q) and unresponsive or refractory to erythropoiesis. https://​ash.​confex.​com/​ash/​2014/​webprogram/​Paper70494.​html. Accessed 13 April 2015.
89.
go back to reference Sibon D, Cannas G, Baracco F, Prebet T, Vey N, Banos A, Besson C, Corm S, Blanc M, Slama B, Perrier H, Fenaux P, Wattel E. Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents. Br J Haematol. 2012;156(5):619–25.PubMedCrossRef Sibon D, Cannas G, Baracco F, Prebet T, Vey N, Banos A, Besson C, Corm S, Blanc M, Slama B, Perrier H, Fenaux P, Wattel E. Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents. Br J Haematol. 2012;156(5):619–25.PubMedCrossRef
90.
go back to reference Komrokji RS, Lancet JE, Swern AS, Chen N, Paleveda J, Lush R, Saba HI, List AF. Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome. Blood. 2012;120(17):3419–24.PubMedCrossRef Komrokji RS, Lancet JE, Swern AS, Chen N, Paleveda J, Lush R, Saba HI, List AF. Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome. Blood. 2012;120(17):3419–24.PubMedCrossRef
91.
go back to reference Passweg JR, Giagounidis AAN, Simcock M, Aul C, Dobbelstein C, Stadler M, Ossenkoppele G, Hofmann W-K, Schilling K, Tichelli A, Ganser A. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care—SAKK 33/99. J Clin Oncol. 2011;29(3):303–9.PubMedCrossRef Passweg JR, Giagounidis AAN, Simcock M, Aul C, Dobbelstein C, Stadler M, Ossenkoppele G, Hofmann W-K, Schilling K, Tichelli A, Ganser A. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care—SAKK 33/99. J Clin Oncol. 2011;29(3):303–9.PubMedCrossRef
92.
go back to reference Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008;26(15):2505–11.PubMedCrossRef Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008;26(15):2505–11.PubMedCrossRef
93.
go back to reference Saunthararajah Y, Nakamura R, Wesley R, Wang QJ, Barrett AJ. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood. 2003;102(8):3025–7.PubMedCrossRef Saunthararajah Y, Nakamura R, Wesley R, Wang QJ, Barrett AJ. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood. 2003;102(8):3025–7.PubMedCrossRef
94.
go back to reference Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL, McIntyre HJ, Fernando IJ, Backstrom JT, Beach CL. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009;27(11):1850–6.PubMedCrossRef Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL, McIntyre HJ, Fernando IJ, Backstrom JT, Beach CL. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009;27(11):1850–6.PubMedCrossRef
95.
go back to reference Hahn T, McCarthy PL, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, Isola LM, Lazarus HM, Lee SJ, Lemaistre CF, Loberiza F, Maziarz RT, Rizzo JD, Joffe S, Parsons S, Majhail NS. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31(19):2437–49.PubMedCentralPubMedCrossRef Hahn T, McCarthy PL, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, Isola LM, Lazarus HM, Lee SJ, Lemaistre CF, Loberiza F, Maziarz RT, Rizzo JD, Joffe S, Parsons S, Majhail NS. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31(19):2437–49.PubMedCentralPubMedCrossRef
96.
go back to reference Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A, Beelen D, Devergie A, Alessandrino E, Willemze R, Ruutu T, Boogaerts M, Falda M, Jouet J-P, Niederwieser D, Kroger N, Mufti GJ, De Witte TM. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol. 2010;28(3):405–11.PubMedCrossRef Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A, Beelen D, Devergie A, Alessandrino E, Willemze R, Ruutu T, Boogaerts M, Falda M, Jouet J-P, Niederwieser D, Kroger N, Mufti GJ, De Witte TM. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol. 2010;28(3):405–11.PubMedCrossRef
97.
go back to reference McClune BL, Weisdorf DJ, Pedersen TL, Da Silva GT, Tallman MS, Sierra J, DiPersio J, Keating A, Gale RP, George B, Gupta V, Hahn T, Isola L, Jagasia M, Lazarus H, Marks D, Maziarz R, Waller EK, Bredeson C, Giralt S. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28(11):1878–87.PubMedCentralPubMedCrossRef McClune BL, Weisdorf DJ, Pedersen TL, Da Silva GT, Tallman MS, Sierra J, DiPersio J, Keating A, Gale RP, George B, Gupta V, Hahn T, Isola L, Jagasia M, Lazarus H, Marks D, Maziarz R, Waller EK, Bredeson C, Giralt S. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28(11):1878–87.PubMedCentralPubMedCrossRef
98.
go back to reference Tamari R, Castro-Malaspina H. Transplant for MDS: Challenges and emerging strategies. Best Pract Res Clin Haematol. 2015;28(1):43–54.PubMedCrossRef Tamari R, Castro-Malaspina H. Transplant for MDS: Challenges and emerging strategies. Best Pract Res Clin Haematol. 2015;28(1):43–54.PubMedCrossRef
99.
go back to reference Atallah E, Bylow K, Troy J, Saber W. Treatment of older patients with high-risk myelodysplastic syndromes (MDS): the emerging role of allogeneic hematopoietic stem cell transplantation (allo HSCT). Curr Hematol Malig Rep. 2014;9(1):57–65.PubMedCentralPubMedCrossRef Atallah E, Bylow K, Troy J, Saber W. Treatment of older patients with high-risk myelodysplastic syndromes (MDS): the emerging role of allogeneic hematopoietic stem cell transplantation (allo HSCT). Curr Hematol Malig Rep. 2014;9(1):57–65.PubMedCentralPubMedCrossRef
100.
go back to reference Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C, Maloney DG, Storb R. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004;104(4):961–8.PubMedCrossRef Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C, Maloney DG, Storb R. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004;104(4):961–8.PubMedCrossRef
101.
go back to reference Zipperer E, Pelz D, Nachtkamp K, Kuendgen A, Strupp C, Gattermann N, Haas R, Germing U. The hematopoietic stem cell transplantation comorbidity index is of prognostic relevance for patients with myelodysplastic syndrome. Haematologica. 2009;94(5):729–32.PubMedCentralPubMedCrossRef Zipperer E, Pelz D, Nachtkamp K, Kuendgen A, Strupp C, Gattermann N, Haas R, Germing U. The hematopoietic stem cell transplantation comorbidity index is of prognostic relevance for patients with myelodysplastic syndrome. Haematologica. 2009;94(5):729–32.PubMedCentralPubMedCrossRef
102.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRef Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRef
103.
go back to reference Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912–9.PubMedCentralPubMedCrossRef Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912–9.PubMedCentralPubMedCrossRef
104.
go back to reference Sorror ML, Martin PJ, Storb RF, Bhatia S, Maziarz RT, Pulsipher MA, Maris MB, Davis C, Deeg HJ, Lee SJ, Maloney DG, Sandmaier BM, Appelbaum FR, Gooley TA. Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality. Blood. 2014;124(2):287–95.PubMedCentralPubMedCrossRef Sorror ML, Martin PJ, Storb RF, Bhatia S, Maziarz RT, Pulsipher MA, Maris MB, Davis C, Deeg HJ, Lee SJ, Maloney DG, Sandmaier BM, Appelbaum FR, Gooley TA. Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality. Blood. 2014;124(2):287–95.PubMedCentralPubMedCrossRef
105.
go back to reference Sorror ML, Estey E. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults. Hematol Am Soc Hematol Educ Program. 2014;2014(1):21–33.CrossRef Sorror ML, Estey E. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults. Hematol Am Soc Hematol Educ Program. 2014;2014(1):21–33.CrossRef
106.
go back to reference Hoyle CF, de Bastos M, Wheatley K, Sherrington PD, Fischer PJ, Rees JK, Gray R, Hayhoe FG. AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC’s 9th AML trial. Br J Haematol. 1989;72(1):45–53.PubMedCrossRef Hoyle CF, de Bastos M, Wheatley K, Sherrington PD, Fischer PJ, Rees JK, Gray R, Hayhoe FG. AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC’s 9th AML trial. Br J Haematol. 1989;72(1):45–53.PubMedCrossRef
107.
go back to reference Kantarjian HM, Estey EH, Keating MJ. Treatment of therapy-related leukemia and myelodysplastic syndrome. Hematol Oncol Clin N Am. 1993;7(1):81–107. Kantarjian HM, Estey EH, Keating MJ. Treatment of therapy-related leukemia and myelodysplastic syndrome. Hematol Oncol Clin N Am. 1993;7(1):81–107.
108.
go back to reference Estey EH, Keating MJ, McCredie KB, Bodey GP, Freireich EJ. Causes of initial remission induction failure in acute myelogenous leukemia. Blood. 1982;60(2):309–15.PubMed Estey EH, Keating MJ, McCredie KB, Bodey GP, Freireich EJ. Causes of initial remission induction failure in acute myelogenous leukemia. Blood. 1982;60(2):309–15.PubMed
109.
go back to reference Cheson BD, Jasperse DM, Simon R, Friedman MA. A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes. J Clin Oncol. 1986;4(12):1857–64.PubMed Cheson BD, Jasperse DM, Simon R, Friedman MA. A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes. J Clin Oncol. 1986;4(12):1857–64.PubMed
110.
go back to reference Cheson BD, Simon R. Low-dose ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes: a review of 20 years’ experience. Semin Oncol. 1987;14(2 Suppl 1):126–33.PubMed Cheson BD, Simon R. Low-dose ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes: a review of 20 years’ experience. Semin Oncol. 1987;14(2 Suppl 1):126–33.PubMed
111.
go back to reference Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.PubMedCentralPubMedCrossRef Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.PubMedCentralPubMedCrossRef
112.
go back to reference Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellström-Lindberg E, Santini V, List AF, Gore SD, Backstrom J, McKenzie D, Beach CL. Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol/Hematol. 2010;76(3):218–27.CrossRef Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellström-Lindberg E, Santini V, List AF, Gore SD, Backstrom J, McKenzie D, Beach CL. Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol/Hematol. 2010;76(3):218–27.CrossRef
113.
go back to reference Gore SD, Fenaux P, Santini V, Bennett JM, Silverman LR, Seymour JF, Hellström-Lindberg E, Swern AS, Beach CL, List AF. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. 2013;98(7):1067–72.PubMedCentralPubMedCrossRef Gore SD, Fenaux P, Santini V, Bennett JM, Silverman LR, Seymour JF, Hellström-Lindberg E, Swern AS, Beach CL, List AF. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. 2013;98(7):1067–72.PubMedCentralPubMedCrossRef
114.
go back to reference García-Delgado R, de Miguel D, Bailén A, González JR, Bargay J, Falantes JF, Andreu R, Ramos F, Tormo M, Brunet S, Figueredo A, Casaño J, Medina Á, Badiella L, Jurado AF, Sanz G. Effectiveness and safety of different azacitidine dosage regimens in patients with myelodysplastic syndromes or acute myeloid leukemia. Leuk Res. 2014;38(7):744–50.PubMedCrossRef García-Delgado R, de Miguel D, Bailén A, González JR, Bargay J, Falantes JF, Andreu R, Ramos F, Tormo M, Brunet S, Figueredo A, Casaño J, Medina Á, Badiella L, Jurado AF, Sanz G. Effectiveness and safety of different azacitidine dosage regimens in patients with myelodysplastic syndromes or acute myeloid leukemia. Leuk Res. 2014;38(7):744–50.PubMedCrossRef
115.
go back to reference Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, Laille E, Giordano H, Sakoian S, Jabbour E, Kantarjian H, Skikne B. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29(18):2521–7.PubMedCentralPubMedCrossRef Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, Laille E, Giordano H, Sakoian S, Jabbour E, Kantarjian H, Skikne B. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29(18):2521–7.PubMedCentralPubMedCrossRef
116.
go back to reference Zeidan AM, Lee J-W, Prebet T, Greenberg P, Sun Z, Juckett M, Smith MR, Paietta E, Gabrilove J, Erba HP, Katterling RP, Tallman MS, Gore SD. Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS. Br J Haematol. 2014;167:62–8.PubMedCentralPubMedCrossRef Zeidan AM, Lee J-W, Prebet T, Greenberg P, Sun Z, Juckett M, Smith MR, Paietta E, Gabrilove J, Erba HP, Katterling RP, Tallman MS, Gore SD. Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS. Br J Haematol. 2014;167:62–8.PubMedCentralPubMedCrossRef
117.
go back to reference van der Helm LH, Alhan C, Wijermans PW, van Marwijk Kooy M, Schaafsma R, Biemond BJ, Beeker A, Hoogendoorn M, van Rees BP, de Weerdt O, Wegman J, Libourel WJ, Luykx-de Bakker SA, Minnema MC, Brouwer RE, Croon-de Boer F, Eefting M, Jie KSG, van de Loosdrecht AA, Koedam J, Veeger GM, Vellenga E, Huls G. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named p”. Br. J. Haematol. 2011;155(5):599–606.PubMedCrossRef van der Helm LH, Alhan C, Wijermans PW, van Marwijk Kooy M, Schaafsma R, Biemond BJ, Beeker A, Hoogendoorn M, van Rees BP, de Weerdt O, Wegman J, Libourel WJ, Luykx-de Bakker SA, Minnema MC, Brouwer RE, Croon-de Boer F, Eefting M, Jie KSG, van de Loosdrecht AA, Koedam J, Veeger GM, Vellenga E, Huls G. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named p”. Br. J. Haematol. 2011;155(5):599–606.PubMedCrossRef
118.
go back to reference Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-Ladaga A, Zaneveld J, Wang H, Caughey B, Stojanov P, Getz G, Garcia-Manero G, Kantarjian H, Chen R, Stone RM, Neuberg D, Steensma DP, Ebert BL. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124(17):2705–12.PubMedCentralPubMedCrossRef Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-Ladaga A, Zaneveld J, Wang H, Caughey B, Stojanov P, Getz G, Garcia-Manero G, Kantarjian H, Chen R, Stone RM, Neuberg D, Steensma DP, Ebert BL. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124(17):2705–12.PubMedCentralPubMedCrossRef
119.
go back to reference Itzykson R, Kosmider O, Cluzeau T, Mansat-De Mas V, Dreyfus F, Beyne-Rauzy O, Quesnel B, Vey N, Gelsi-Boyer V, Raynaud S, Preudhomme C, Adès L, Fenaux P, Fontenay M. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2011;25(7):1147–52.CrossRef Itzykson R, Kosmider O, Cluzeau T, Mansat-De Mas V, Dreyfus F, Beyne-Rauzy O, Quesnel B, Vey N, Gelsi-Boyer V, Raynaud S, Preudhomme C, Adès L, Fenaux P, Fontenay M. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leuk Off J Leuk Soc Am Leuk Res Fund UK. 2011;25(7):1147–52.CrossRef
120.
go back to reference Itzykson R, Thépot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Salanoubat C, Visanica S, Stamatoullas A, Isnard F, Marfaing-Koka A, De Botton S, Chelghoum Y, Taksin AL, Plantier I, Ame S, Boehrer S, Gardin C, Beach CL, Adès L, Fenaux P. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403–11.PubMedCrossRef Itzykson R, Thépot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, Vey N, Recher C, Dartigeas C, Legros L, Delaunay J, Salanoubat C, Visanica S, Stamatoullas A, Isnard F, Marfaing-Koka A, De Botton S, Chelghoum Y, Taksin AL, Plantier I, Ame S, Boehrer S, Gardin C, Beach CL, Adès L, Fenaux P. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403–11.PubMedCrossRef
121.
go back to reference Prébet T, Gore SD, Esterni B, Gardin C, Itzykson R, Thepot S, Dreyfus F, Rauzy OB, Recher C, Adès L, Quesnel B, Beach CL, Fenaux P, Vey N. Outcome of high-risk myelodysplastic syndrome after azacitidine Treatment failure. J Clin Oncol. 2011;29(24):3322–7.PubMedCrossRef Prébet T, Gore SD, Esterni B, Gardin C, Itzykson R, Thepot S, Dreyfus F, Rauzy OB, Recher C, Adès L, Quesnel B, Beach CL, Fenaux P, Vey N. Outcome of high-risk myelodysplastic syndrome after azacitidine Treatment failure. J Clin Oncol. 2011;29(24):3322–7.PubMedCrossRef
122.
go back to reference Komrokji RS, Raza A, Lancet JE, Ren C, Taft D, Maniar M, Wilhelm F, List AF. Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes. Br J Haematol. 2013;162(4):517–24.PubMedPubMedCentralCrossRef Komrokji RS, Raza A, Lancet JE, Ren C, Taft D, Maniar M, Wilhelm F, List AF. Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes. Br J Haematol. 2013;162(4):517–24.PubMedPubMedCentralCrossRef
123.
go back to reference Garcia-Manero G, Fenaux P, Al-Kali A, Baer MR, Sekeres MA, Roboz G, Gaidano G, Scott BL, Greenberg PL, Platzbecker U, Steensma DP, Kambhampati S, Kreuzer K-A, Godley LA, Collins R, Atallah E, Wilhelm F, Wilhelm I, Azarnia N, Maniar M, Silverman LR. Overall survival and subgroup analysis from a randomized phase III study of intravenous rigosertib versus best supportive care (BSC) in patients (pts) with higher-risk myelodysplastic syndrome (HR-MDS) after failure of hypomethylating agents (HMAs). Blood. 2014;124:163.CrossRef Garcia-Manero G, Fenaux P, Al-Kali A, Baer MR, Sekeres MA, Roboz G, Gaidano G, Scott BL, Greenberg PL, Platzbecker U, Steensma DP, Kambhampati S, Kreuzer K-A, Godley LA, Collins R, Atallah E, Wilhelm F, Wilhelm I, Azarnia N, Maniar M, Silverman LR. Overall survival and subgroup analysis from a randomized phase III study of intravenous rigosertib versus best supportive care (BSC) in patients (pts) with higher-risk myelodysplastic syndrome (HR-MDS) after failure of hypomethylating agents (HMAs). Blood. 2014;124:163.CrossRef
124.
go back to reference Kantarjian H, Issa J-PJ, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794–1803.PubMedCrossRef Kantarjian H, Issa J-PJ, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794–1803.PubMedCrossRef
125.
go back to reference Lee YG, Kim I, Yoon SS, Park S, Cheong JW, Min YH, Lee JO, Bang SM, Yi HG, Kim CS, Park Y, Kim BS, Mun YC, Seong CM, Park J, Lee JH, Kim SY, Lee HG, Kim YK, Kim HJ. Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes. Br J Haematol. 2013;161(3):339–47.PubMedCrossRef Lee YG, Kim I, Yoon SS, Park S, Cheong JW, Min YH, Lee JO, Bang SM, Yi HG, Kim CS, Park Y, Kim BS, Mun YC, Seong CM, Park J, Lee JH, Kim SY, Lee HG, Kim YK, Kim HJ. Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes. Br J Haematol. 2013;161(3):339–47.PubMedCrossRef
126.
go back to reference Lee JH, Choi Y, Kim SD, Kim DY, Lee JH, Lee KH, Lee SM, Cho SH, Lee WS, Joo YD. Comparison of 7-day azacitidine and 5-day decitabine for treating myelodysplastic syndrome. Ann Hematol. 2013;92(7):889–97.PubMedCrossRef Lee JH, Choi Y, Kim SD, Kim DY, Lee JH, Lee KH, Lee SM, Cho SH, Lee WS, Joo YD. Comparison of 7-day azacitidine and 5-day decitabine for treating myelodysplastic syndrome. Ann Hematol. 2013;92(7):889–97.PubMedCrossRef
127.
go back to reference Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JPJ, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. 2007;110(7):2302–8.PubMedCrossRef Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JPJ, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. 2007;110(7):2302–8.PubMedCrossRef
128.
go back to reference Kuendgen A, Bug G, Ottmann OG, Haase D, Schanz J, Hildebrandt B, Nachtkamp K, Neukirchen J, Dienst A, Haas R, Germing U, Gattermann N. Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid. Clin Epigenet. 2011;2(2):389–99.CrossRef Kuendgen A, Bug G, Ottmann OG, Haase D, Schanz J, Hildebrandt B, Nachtkamp K, Neukirchen J, Dienst A, Haas R, Germing U, Gattermann N. Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid. Clin Epigenet. 2011;2(2):389–99.CrossRef
129.
go back to reference Silverman LR, Amit V, Odchimar-Reissig R, Feldman EJ, Navada SC, Demakos EP, Baer MR, Najfeld V, Sparano J, Piekarz R. A phase II trial of epigenetic modulators vorinostat in combination with azacitidine (azaC) in patients with the myelodysplastic syndrome: initial results of study 6898 of the New Yorker Cancer Consortium. Blood. 2013;122 (21):386. Silverman LR, Amit V, Odchimar-Reissig R, Feldman EJ, Navada SC, Demakos EP, Baer MR, Najfeld V, Sparano J, Piekarz R. A phase II trial of epigenetic modulators vorinostat in combination with azacitidine (azaC) in patients with the myelodysplastic syndrome: initial results of study 6898 of the New Yorker Cancer Consortium. Blood. 2013;122 (21):386.
130.
go back to reference Scott BL, Ramakrishnan A, Storer B, Becker PS, Petersdorf S, Estey EH, Deeg HJ. Prolonged responses in patients with MDS and CMML treated with azacitidine and etanercept: short report. Br J Haematol. 2010;148(6):944–7.PubMedCentralPubMedCrossRef Scott BL, Ramakrishnan A, Storer B, Becker PS, Petersdorf S, Estey EH, Deeg HJ. Prolonged responses in patients with MDS and CMML treated with azacitidine and etanercept: short report. Br J Haematol. 2010;148(6):944–7.PubMedCentralPubMedCrossRef
131.
go back to reference Liesveld JL, Rosell KE, Bechelli J, Lu C, Messina P, Mulford D, Ifthikharuddin JJ, Jordan CT, Phillips Ii GL. Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines. Cancer Invest. 2011;29(7):439–50.PubMedCentralPubMed Liesveld JL, Rosell KE, Bechelli J, Lu C, Messina P, Mulford D, Ifthikharuddin JJ, Jordan CT, Phillips Ii GL. Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines. Cancer Invest. 2011;29(7):439–50.PubMedCentralPubMed
Metadata
Title
Myelodysplastic Syndromes in the Elderly: Treatment Options and Personalized Management
Authors
Sonja Burgstaller
Petra Wiesinger
Reinhard Stauder
Publication date
01-11-2015
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 11/2015
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-015-0312-7

Other articles of this Issue 11/2015

Drugs & Aging 11/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.