Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly

https://doi.org/10.1016/j.cger.2015.08.010Get rights and content

Section snippets

Key points

  • Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic disorders with variable natural history.

  • Treatment recommendations for MDS are risk adapted and range from supportive care to high-intensity therapy.

  • Optimal therapy for older patients with acute myeloid leukemia (AML) is unclear.

  • Management of older adults with MDS and AML needs to be individualized, accounting for both the heterogeneity of disease biology and patient characteristics, which can influence life expectancy and

Myelodysplastic syndromes

Myelodysplastic syndromes (MDS) constitute a heterogenous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis and peripheral blood cytopenias. MDS can be indolent or rapidly progressive with complications secondary to profound cytopenias and the risk of evolution into acute myeloid leukemia (AML). MDS also impair quality of life, and are associated with high symptom burden1 and high rates of health care use. Estimated 3-year survival rates are less than 50% in

Acute myeloid leukemia

AML refers to a group of clonal hematopoietic disorders characterized by proliferation of immature myeloid cells in the bone marrow. Accumulation of leukemic cells impairs the normal hematopoietic function, resulting in cytopenias with or without leukocytosis. AML is most commonly diagnosed among older adults (median age, 68–72 years).3 In 2014, the American Cancer Society estimated that 18,860 patients would be diagnosed with AML, with most (10,460) anticipated to die from the disease.26

Summary

MDS and AML are heterogeneous diseases affecting older adults. Significant advances are being made in understanding the complexity of both tumor biology and the patient characteristics that influence outcomes. Optimal treatment decision making requires a frank discussion regarding risks and benefits of therapy interpreted in the context of individualized assessment and each patient’s values and goals of care.

First page preview

First page preview
Click to open first page preview

References (68)

  • G. Juliusson et al.

    Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry

    Blood

    (2009)
  • S.S. Farag et al.

    Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461

    Blood

    (2006)
  • D. Grimwade et al.

    The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial

    Blood

    (2001)
  • C.P. Leith et al.

    Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study

    Blood

    (1997)
  • S. Castaigne et al.

    Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study

    Lancet

    (2012)
  • M.R. Baer et al.

    Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720

    Blood

    (2002)
  • H. Dombret et al.

    International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts

    Blood

    (2015)
  • R.M. Stone et al.

    Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine

    Blood

    (2001)
  • U. Krug et al.

    Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes

    Lancet

    (2010)
  • C. Rollig et al.

    A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial

    Blood

    (2010)
  • H.D. Klepin et al.

    Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia

    Blood

    (2013)
  • A.E. Sherman et al.

    Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes

    Leuk Res

    (2013)
  • S.M. Alibhai et al.

    Quality of life and physical function in adults treated with intensive chemotherapy for acute myeloid leukemia improve over time independent of age

    J Geriatr Oncol

    (2015)
  • H. Mohamedali et al.

    Older age is associated with similar quality of life and physical function compared to younger age during intensive chemotherapy for acute myeloid leukemia

    Leuk Res

    (2012)
  • F. Efficace et al.

    Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

    Br J Haematol

    (2015)
  • SEER cancer statistics review 1975-2009. 2012. Available at: www.seer.cancer.gov. Accessed July 21,...
  • M.T. Voso et al.

    Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database

    J Clin Oncol

    (2013)
  • M.G. Della Porta et al.

    Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome

    Haematologica

    (2011)
  • N. Daver et al.

    Impact of comorbidities by ACE-27 in the revised-IPSS for patients with myelodysplastic syndromes

    Am J Hematol

    (2014)
  • K. Naqvi et al.

    Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model

    J Clin Oncol

    (2011)
  • B. Deschler et al.

    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)
  • M. Jadersten et al.

    Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome

    J Clin Oncol

    (2008)
  • V. Moyo et al.

    Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis

    Ann Hematol

    (2008)
  • L.R. Silverman et al.

    Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B

    J Clin Oncol

    (2002)
  • Cited by (31)

    • Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome

      2022, Blood Advances
      Citation Excerpt :

      The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal stem cell disorders caused by ineffective hematopoiesis determining a maturation arrest in the bone marrow and pancytopenia in the peripheral blood. MDS predominantly occurs in the elderly, with most patients diagnosed after the age of 60 years.1,2 Low-risk patients (those with a Revised International Prognostic Scoring System [IPSS-R] score of <3.5 points) have a median 4-year survival of 80%, but patients with higher-risk MDS (HR-MDS;IPSS-R ≥ 3.5) have poor prognosis and experience rapid progression, with a median survival of <1 year.3

    • The USP7-TRIM27 axis mediates non-canonical PRC1.1 function and is a druggable target in leukemia

      2021, iScience
      Citation Excerpt :

      Dependent on risk category, overall survival for adult AML patients varies between 10% and 60% (Arber et al., 2016; Burnett et al., 2011). AML mostly affects the elderly, as 75% of the cases occur in patients >60 years of age, who have a particularly poor outcome (Klepin, 2016; Rucker et al., 2012). These older patients usually have karyotypes associated with unfavorable risk and also TP53 mutations, and do not respond well to standard chemotherapy (Bowen et al., 2009; Hou et al., 2015; Rucker et al., 2012).

    • Not type of induction therapy but consolidation with allogeneic hematopoietic cell transplantation determines outcome in older AML patients: A single center experience of 355 consecutive patients

      2019, Leukemia Research
      Citation Excerpt :

      In clinical practice the optimal management of AML in older patients is challenging [8]. Older patients are often considered not eligible for treatment with IC, due to poor performance status and/or inadequate organ function which can lead to excessive toxicity and treatment-related mortality [6,9,10]. Additionally, disease related factors such as cytogenetic abnormalities, which are more frequent in older patients, might render the disease less sensitive to chemotherapy [1,11,12].

    • New Concepts in the Manipulation of the Aging Process

      2024, Current Stem Cell Research and Therapy
    View all citing articles on Scopus

    Disclosure: Dr H.D. Klepin is supported by a Paul Beeson Career Development Award in Aging Research (K23AG038361; supported by NIA, AFAR, The John A. Hartford Foundation, and The Atlantic Philanthropies), The Gabrielle's Angel Foundation for Cancer Research, and NCI Cancer Center Support Grant (CCSG) P30CA012197. Dr H.D. Klepin has no other disclosures.

    View full text