The myelodysplastic syndromes

Published on 03/04/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

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The myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are a group of clonal disorders of the bone marrow. Their common feature is bone marrow failure as a result of ineffective haematopoiesis rather than reduced haematopoietic activity. A hypercellular marrow and peripheral blood cytopenia with characteristic dysplastic morphological abnormalities form the basis for diagnosis. In early disease there is increased apoptosis of marrow progenitors causing peripheral blood cytopenia but in later MDS there is actually decreased apoptosis with characteristic gene mutations, enhanced survival of myeloblasts and potential expansion of a leukaemic clone. Patients may develop frank acute myeloid leukaemia (AML; see p. 40). Increased marrow angiogenesis and autoimmunity also occur.

MDS is predominantly a disease of the elderly, although it may affect all ages. It can arise de novo or follow previous chemotherapy or radiotherapy for another malignancy. It seems to be increasing in incidence.

Classification

This is not straightforward. The French-American-British (FAB) classification divides MDS into five subtypes depending on morphological features and particularly the number of blood and marrow leukaemic blast cells. The more recent WHO system (Table 25.1) divides MDS into unilineage or multilineage dysplasia, refractory anaemia with ring sideroblasts and dysplasia with excess blasts. The FAB entity chronic myelomonocytic leukaemia (CMML) is now included in the overlap ‘MDS with myeloproliferative disorder’ category. It is likely that cytogenetic and molecular abnormalities will be increasingly incorporated into the classification; a current example is 5q− syndrome, a distinct subtype of MDS associated with a response to novel therapy and a good prognosis.

Clinical features

The diagnosis may follow a routine blood count in an asymptomatic patient. Where symptoms do occur they range from a mild anaemia to the consequences of severe marrow failure with profound anaemia, leucopenia and thrombocytopenia (Fig 25.1). Abnormal haematopoiesis can cause functional abnormalities of cells, and infection and haemorrhage may be more severe than would be predicted from the degree of cytopenia. Pronounced symptoms are predictably more common in the subtypes with increased blast cells. CMML, like the acute monocytic leukaemias, has specific features including splenomegaly (rare in other forms of MDS), skin infiltration and serous effusions.

Diagnosis

Morphology

The diagnosis of MDS depends on careful morphological examination of the blood film and bone marrow aspirate and trephine specimens (Fig 25.2). Common abnormalities include:

Where there are changes in all three lines the term ‘trilineage dysplasia’ is used. The bone marrow trephine biopsy usually confirms marrow hypercellularity, although fibrosis and even hypocellularity may occur.

Treatment

Specific treatments

Treatment needs to be individualised according to the type of disease and age of the patient.

High-risk MDS

In high-risk MDS (e.g. RAEB; see Table 25.1), the primary aim is to prolong survival and delay transformation to AML. In younger patients, AML-type chemotherapy and allogeneic stem cell transplantation, the only potentially curative treatment, are possible options. The hypomethylating agent azacitidine has shown efficacy in higher risk subgroups with significantly prolonged survivals and delay of onset of AML. It is given subcutaneously as outpatient therapy and is generally well tolerated.