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CHAPTER 26 Myelodysplasia
Domenico Fusco, Andrea Bellieni, Beatrice Di Capua, and Giuseppe Colloca
Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
Introduction
The myelodysplastic syndromes (MDSs) are a heterogeneous group of malignant hematopoietic stem cell disorders characterized by cytopenia due to dysplastic and ineffective blood cell production and potential variable risk of transformation to acute leukaemia.1,2 These disorders are sporadic and arise de novo or may result after exposure to certain forms of environmental toxins (e.g. benzene), radiation (e.g. therapeutic or accidental), and chemotherapy exposure as alkylating agents (secondary MDS).3,4 MDS primarily affects older patients, with an onset mean age over 70 and an increased incidence with advancing age.5,6 The secondary MDSs are not age‐related, although they are extremely rare in children, where monocytic leukaemia can be observed. The incidence has increased over time because of the increased recognition of this disease by medical doctors, as well as the ageing of the population. The demographics in developed countries shift toward older patient populations due to increased longevity and better quality of healthcare, so more people are receiving intensive treatments like chemotherapy.
MDS may easily be overlooked in elderly patients. It can present simply as a chronic macrocytic anaemia, and there may be a tendency to ‘leave well enough alone’ in an older patient with multiple comorbidities.
However, our understanding of MDS continues to improve, so we can use geriatric knowledge in assessing complex older and oldest‐old patients, to recognize and measure frailty and identify fit and the unfit patients. Better treatment strategies have been developed to prolong life and delay transformation to acute leukaemia, reducing the risk of major complications such as anaemia, bleeding, and severe infections. The majority of patients cannot tolerate intensive therapeutic approaches such as allogeneic hematopoietic stem cell transplantation. For this reason, treatment needs to be risk‐adapted and tailored to the frail old patient, involving the definition of different goals of therapy according to the risk status of the patient.7
Epidemiology and clinical presentation
Myelodysplastic syndromes are the most common hematologic neoplasms in the elderly, and the incidence of MDS in the US is expected to double from 2000 to 2030 as the result of population ageing.8,9
The exact incidence of de novo MDS remains unclear but appears to be greater than the incidence of acute myelogenous leukaemia (AML).10 The SEER (Surveillance, Epidemiology, and End Results) Program first began collecting information on MSD in 2001, and the first three years of data showed a median age of 76 at MDS diagnosis, with almost all cases (86%) occurring in individuals 60 and older.11
The epidemiology of MDS is reflective of the disease biology, which is likely a consequence of the ageing process. Indeed, age is the primary risk factor for developing MDS; as human age, hematopoietic stem cells tend to accumulate mutations in DNA.
Conservative estimates from cancer databases suggest that approximately 10,000 cases are diagnosed annually in the US.11,12 The actual incidence of MDS is likely higher than that predicted by cancer databases since nonspecific symptoms may evade detection in the early stages of the disease and suspected cases may not undergo definitive testing (i.e. bone marrow biopsy) due to comorbidities. Investigations that have analysed reimbursement claims have estimated the incidence in the US to be 30,000 to 40,000 new cases per year.13,14
The risk of developing MDS increases with age. The estimated incidence in the SEER‐Medicare population is 75 cases per 100,000 people over age 65 compared to 20 cases per 100,000 previously reported by SEER alone, suggesting
