Impact of Age and Comorbidity in Myelodysplastic Syndromes

View More View Less
  • a From the Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria; 3rd Medical Deptartment for Hematology and Oncology, Hanusch Hospital and Ludwig-Boltzmann Institute for Leukemia Research and Hematology, Vienna, Austria; Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria; and First Department of Internal Medicine, Elisabethinen Hospital, Linz, Austria.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are preferentially diagnosed in the elderly. With the increase in older patients with MDS in the Western world and the availability of more therapeutic options, new strategies and algorithms for optimal management and treatment of these patients must be developed. Although age is recognized as an important adverse variable affecting survival, most scoring systems have not included age in score risk calculations. Comorbidity is of particular importance and a frequent covariable in elderly patients with MDS. However, although comorbidity scores have been established and used for risk assessment in younger high-risk patients scheduled to undergo intensive therapy, these scores are only just being applied to elderly patients, with relevant results. Advanced age should not exclude a patient with MDS from appropriate treatment, and age alone should not be considered a surrogate marker for functional decline or comorbidities. This article discusses the need to improve scoring systems, individualized risk-assessment, and treatment algorithms for elderly patients with MDS by including age and comorbidities.

Correspondence: Reinhard Stauder, MD, MSc, Division of Hematology and Oncology, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail: reinhard.stauder@i-med.ac.at
  • 1.

    Hofmann WK, Koeffler HP. Myelodysplastic syndrome. Annu Rev Med 2005;56:116.

  • 2.

    Valent P, Horny HP, Bennett JM et al.. Definitions and standards in the diagnosis and treatment of myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res 2007;31:727736.

    • Search Google Scholar
    • Export Citation
  • 3.

    Greenberg P, Cox C, LeBeau MM et al.. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:20792088.

  • 4.

    Germing U, Hildebrandt B, Pfeilstöcker M et al.. Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia 2005;19:22232231.

    • Search Google Scholar
    • Export Citation
  • 5.

    Malcovati L, Porta MG, Pascutto C et al.. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005;23:75947603.

    • Search Google Scholar
    • Export Citation
  • 6.

    Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica 2006;91:15881590.

    • Search Google Scholar
    • Export Citation
  • 7.

    Malcovati L, Germing U, Kuendgen A et al.. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007;25:35033510.

    • Search Google Scholar
    • Export Citation
  • 8.

    Carreca I, Balducci L, Extermann M. Cancer in the older person. Cancer Treat Rev 2005;31:380402.

  • 9.

    Aul C, Gattermann N, Heyll A et al.. Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 1992;6:5259.

    • Search Google Scholar
    • Export Citation
  • 10.

    Rocco G, Oberaigner W, Gastl G et al.. Myelodysplastic syndrome and acute myeloid leukemia in Tyrol: incidence and distribution [abstract]. Onkologie 2003;23(Suppl 5):S121. Abstract P683.

    • Search Google Scholar
    • Export Citation
  • 11.

    Germing U, Strupp C, Kundgen A et al.. No increase in age-specific incidence of myelodysplastic syndromes. Haematologica 2004;89:905910.

  • 12.

    Pfeilstöcker M, Karlic H, Nösslinger T et al.. Myelodysplastic syndromes, aging, and age: correlations, common mechanisms, and clinical implications. Leuk Lymphoma 2007;48:19001909.

    • Search Google Scholar
    • Export Citation
  • 13.

    Sanz GF, Sanz MA, Greenberg PL. Prognostic factors and scoring systems in myelodysplastic syndromes. Haematologica 1998;83:358368.

  • 14.

    Sanz GF, Sanz MA, Villespi T et al.. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 1989;74:395408.

    • Search Google Scholar
    • Export Citation
  • 15.

    Morel P, Hebbar M, Lai JL et al.. Cytogenetic analysis has strong prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia 1993;7:13151323.

    • Search Google Scholar
    • Export Citation
  • 16.

    Noesslinger T, Tuechler H, Germing U et al.. Individualizing IPSS risk assessment in myelodysplastic syndromes, by additionally taking into account age, gender and French-American-British (FAB) classification – a multicenter analysis [abstract]. Blood 2006,107:Abstract 2618.

    • Search Google Scholar
    • Export Citation
  • 17.

    Kuendgen A, Strupp C, Aivado M et al.. Myelodysplastic syndromes in patients younger than age 50. J Clin Oncol 2006;24:53585365.

  • 18.

    Sanz GF, Sanz MA, Greenberg PL. Prognostic factors and scoring systems in myelodysplastic syndromes. Haematologica 1998;83:358368.

  • 19.

    Balducci L, Baskin R, Cohen HJ et al.. NCCN Clinical Practice Guidelines in Oncology: Senior Adult Oncology. Version 2, 2007. Available at: http://www.nccn.org/professionals/physician_gls/PDF/senior.pdf. Accessed February 25, 2008.

    • Search Google Scholar
    • Export Citation
  • 20.

    Morel P, Declercq C, Hebbar M et al.. Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques. Br J Haematol 1996;94:116119.

    • Search Google Scholar
    • Export Citation
  • 21.

    Feinstein AR. The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis 1970;23:455468.

  • 22.

    Yancik R, Wesley MN, Ries LA et al.. Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer 1998;82:21232134.

    • Search Google Scholar
    • Export Citation
  • 23.

    Lee SJ, Lindquist K, Segal MR, Covinsky KE. Development and validation of a prognostic index for 4-year mortality in older adults. JAMA 2006;295:801808.

    • Search Google Scholar
    • Export Citation
  • 24.

    Satariano WA, Ragland DR. The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med 1994;120:104110.

    • Search Google Scholar
    • Export Citation
  • 25.

    Mitnitski AB, Song X, Rockwood K. The estimation of relative fitness and frailty in community-dwelling older adults using self-report data. J Gerontol A Biol Sci Med Sci 2004;59:M627632.

    • Search Google Scholar
    • Export Citation
  • 26.

    Extermann M. Measuring comorbidity in older cancer patients. Eur J Cancer 2000;36:453471.

  • 27.

    Extermann M. Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol 2000;35:181200.

  • 28.

    Yates JW. Comorbidity considerations in geriatric oncology research. CA Cancer J Clin 2001;51:329336.

  • 29.

    Rao AV, Seo PH, Cohen HJ. Geriatric assessment and comorbidity. Semin Oncol 2004;31:149159.

  • 30.

    de Groot V, Beckerman H, Lankhorst GJ, Bouter LM. How to measure comorbidity. A critical review of available methods. J Clin Epidemiol 2003;56:221229.

    • Search Google Scholar
    • Export Citation
  • 31.

    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;40:373383.

    • Search Google Scholar
    • Export Citation
  • 32.

    Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994;47:12451251.

  • 33.

    Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc 1968;16:622626.

  • 34.

    Miller MD, Paradis CF, Houck PR et al.. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 1992;41:237248.

    • Search Google Scholar
    • Export Citation
  • 35.

    Extermann M, Overcash J, Lyman GH et al.. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 1998;16:15821587.

    • Search Google Scholar
    • Export Citation
  • 36.

    Kaplan MH, Feinstein AR. The importance of classifying initial comorbidity in evaluating the outcome of diabetes mellitus. J Chronic Dis 1974;27:387404.

    • Search Google Scholar
    • Export Citation
  • 37.

    Greenfield S, Blanco DM, Elashoff RM, Ganz PA. Patterns of care related to age of breast cancer patients. JAMA 1987;257:27662770.

  • 38.

    Balducci L. Aging, frailty, and chemotherapy. Cancer Control 2007;14:712.

  • 39.

    Deschler B, de Witte T, Mertelsmann R, Lubbert M. Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: problems and approaches. Haematologica 2006;91:15131522.

    • Search Google Scholar
    • Export Citation
  • 40.

    Pelz D, Nachtkamp K, Kündgen A et al.. Influence of comorbidity factors on the prognosis of patients with myelodysplastic syndromes (MDS). Leuk Res 2007;31(Suppl 1):S3031.

    • Search Google Scholar
    • Export Citation
  • 41.

    Sorror ML, Maris MB, Storer B et al.. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004;104:961968.

    • Search Google Scholar
    • Export Citation
  • 42.

    Diaconescu R, Flowers CR, Storer B et al.. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004;104:15501558.

    • Search Google Scholar
    • Export Citation
  • 43.

    Sorror ML, Maris MB, Storb R et al.. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005;106:29122919.

    • Search Google Scholar
    • Export Citation
  • 44.

    Sorror ML, Sandmaier BM, Storer BE et al.. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 2007;25:42464254.

    • Search Google Scholar
    • Export Citation
  • 45.

    Giles FJ, Borthakur G, Ravandi F et al.. The hematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukemia. Br J Haematol 2007;136:624627.

    • Search Google Scholar
    • Export Citation
  • 46.

    Parimon T, Au DH, Martin PJ, Chien JW. A risk score for mortality after allogeneic hematopoietic cell transplantation. Ann Intern Med 2006;144:407414.

    • Search Google Scholar
    • Export Citation
  • 47.

    Artz AS, Pollyea DA, Kocherginsky M et al.. Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006;12:954964.

    • Search Google Scholar
    • Export Citation
  • 48.

    Della Porta MG, Malcovati L, Travaglino E et al.. A prognostic model for predicting the impact of comorbidities on survival of patients with myelodysplastic syndromes. Blood 2007;110:Abstract 2453.

    • Search Google Scholar
    • Export Citation
  • 49.

    Stauder R, Wimazal F, Nösslinger T et al.. Individualized management and therapy of myelodysplastic syndromes. Wiener Klinische Wochenschrift 2008; in press.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 169 34 3
PDF Downloads 94 33 4
EPUB Downloads 0 0 0