of myelodysplastic syndrome (MDS) in the UK annually and a rising incidence in older patients (over 70 years of age) to 30 cases per 100 000, MDS is far from ...
COMMENT
Myelodysplastic syndrome: 2011 and beyond
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ith approximately 2000 new diagnoses of myelodysplastic syndrome (MDS) in the UK annually and a rising incidence in older patients (over 70 years of age) to 30 cases per 100 000, MDS is far from being the rare disease it was once thought to be (Leukaemia & Lymphoma Research, 2011).The natural history of MDS is highly variable and the condition is still viewed as incurable. Until recently, MDS was not even recognized as a form of cancer; indeed this clonal disorder is characterized by ‘bone marrow failure’ with peripheral blood cytopenias (anaemia, neutropenia or thrombocytopenia or a combination) with a variable risk of progression to acute myeloid leukaemia (AML). Somewhat surprisingly, the majority of patients with MDS die, not from leukaemic progression, but from causes intrinsic to their disease (Dayyani et al, 2010). The diagnosis of MDS requires morphological assessment of blood and bone marrow samples; however, subjective interpretation of samples has led to diagnostic uncertainty. Headway has been made establishing strict diagnostic and subtype classification criteria (World Health Organization, 2008) and it is imperative to risk-stratify patients according to prognosis, thus guiding clinicians with the timely choice of therapy. In the UK, the International Prognostic Scoring System (IPSS) classifies patients into 4 risk groups (low; intermediate-1; intermediate-2; high risk) and are based on 3 parameters: blast percentage, number of cytopenias and type of chromosomal abnormality (Greenberg et al, 1997). Despite its simplicity as a prognostic model and its usage for almost two decades, it has limitations leading to the development of other updated models such as the WHO classification-based Prognostic Scoring System (WPSS) and MD Anderson Cancer Center (MDACC) model (Malcovati et al, 2007; Kantarjian et al, 2008) where newer morphological categories and transfusion requirements are combined with established prognostic variables. Significant strides have been made in our understanding of the molecular pathogenesis of MDS through next-generation sequencing technology that is providing a more complete picture of the spectrum of genetic abnormalities in MDS patients. Among the catalogue of genes, mutations have been identified in genes involved in transcription (RUNX1, TP53) and signal transduction (RAS, JAK2) but a new exciting observation is the deregulation of epigenetic control, deemed relevant in the pathogenesis of MDS. This is achieved through DNA methylation and/or histone modifications, both of which are altered in MDS patients (Shih and Levine, 2011).This may explain
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the benefit in overall survival seen in intermediate-2 and high-risk MDS patients treated with Azacitidine, a hypomethylating agent, leading to it being the first approved drug in MDS therapy (Fenaux et al, 2009).. Following this important landmark, our newfound understanding is paving the way for a novel generation of drugs, exploiting some of these molecular features - and an expansion in the treatment options for MDS patients will only come sooner. Managing MDS in a cash-strapped health system is challenging, especially with increasing patient age and co-morbidities. Stem cell transplantation remains the only curative option but is restricted to younger patients. Novel therapies and best supportive care are the options for the majority of older MDS patients and aims to enhance and prolong their quality of life. Provision of responsive day unit facilities and welltrained staff providing the supportive care measures of blood products, antibiotics and iron chelation required by all patients is essential. Careful evaluation of the functional status of patients by integration of a joint geriatric and haematological service may offer a more personalized approach. Although MDS remains an incurable cancer, the future is promising. Unravelling the full range of epigenetic and genetic abnormalities and their clinical consequences will give us further insight into the pathogenesis of MDS. We believe this will eventually be integrated to provide more robust classification and risk stratification systems and also provide potential targets for new therapeutic agents. It may not be long before we look beyond stem cell BJN transplantation as the only cure for MDS. Dayyani F, Conley AP, Strom SS et al (2010) Cause of death in patients with lower-risk myelodysplastic syndrome. Cancer 116(9): 2174-9 Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al (2009) 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 10(3): 223-32 Epub Greenberg P, Cox C, LeBeau MM et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89(6): 2079-88 Kantarjian H, O’Brien S, Ravandi F et al (2008) Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 113(6):1351-61 Leukaemia & Lymphoma Research (2011) Myelodysplastic syndromes (MDS). http://tinyurl.com/bmy58na (Accessed 29 November 2011) Malcovati L, Germing U, Kuendgen A et al (2007) Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 25(23):3503-10 Shih AH, Levine RL (2011) Molecular biology of myelodysplastic syndromes. Semin Oncol 38(5):613-20 World Health Organization (2008) WHO classification of tumours of haemtopoietic and lymphoid tissues, 4th edn. IARC Press, Lyon
Jessica Okosun, Csaba Bödör and Matthew Smith
Centre for Haemato-Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary, University of London
British Journal of Nursing, 2011, Vol 20, No 22
