MDS describes a range of acquired clonal disorders of bone
marrow. Biologically they are
characterised by maturation abnormalities in one or more haemopoietic cell
lines. Evidence of clonal
abnormality in the form of karyotypic abnormality
may be detected in up to 80% cases. Presentation varies from minor degrees of anaemia to profound
pancytopenia; circulating
blast cells may be present in small numbers.
Bone marrow shows maturation abnormalities with visible blast cell
populations but criteria fall short of those of acute leukaemia. Many myelodysplastic conditions do not progress, some will
progress and ultimately become acute myeloid leukaemia. MDS subtypes
·
Refractory
anaemia (RA) ·
Refractory
anaemia with ringed sideroblasts (RARS) ·
Refractory
anaemia with excess blasts (RAEB) ·
Refractory
anaemia with excess blasts in transformation (RAEB-t) ·
Chronic
myelomonocytic leukaemia Aetiology &
pathogenesis
Incidence of MDS increases with age;
usually >50 years although juvenile MDS is recognised.
Down’s syndrome, previous chemotherapy, chemical exposure (eg
benzene) or irradiation are recognised risk/predisposing factors. Cytogenetic analysis of bone marrow is a key part of the
diagnostic assessment of MDS. Commoner
abnormalities include +8, loss of long arms of 5,7,9,20 or 21 and monosomy
7. Single or complex
abnormalities may be present. Some
abnormalities have prognostic significance e.g. 5q- generally carries a
favourable prognosis whereas monosomy 7 indicates a poor prognosis. Clinical features ·
May be
asymptomatic with minor degrees of macrocytic anaemia identified on FBC
carried out for other reasons, including health screening. ·
Symptomatic
anaemia. ·
Infection (neutropenia
and/or impaired granulocyte function). ·
Bruising or
other haemorrhagic manifestations of thrombocytopenia and/or functionally
deficient platelets. ·
Constitutional
symptoms including weight loss, sweats, etc. usually feature of the more
‘advanced’ subgroups. Management Consists of supportive therapy i.e. transfusion and prompt
treatment of infections, etc. Most
MDS patients are elderly and do not respond to chemotherapy.
Younger patients with RAEB and RAEB-t should be offered intensive
chemotherapy and treated identically to AML.
A minority will be eligible for bone marrow grafting. Specific
prognosis and management of each sub-type are described below. FAB
classification of MDS
MDS FAB Subtype
Blood
Marrow blasts (5%) RA
Monocytes <1%, Blasts <1%
< 5 RARS
Monocytes <1%, Blasts <1%
<5 RAEB
Blasts <5%
5-20 RAEB-t
Blasts – variable
20-30 CMML
Monocytes >1%, Blasts
<5%
<20 Note:
>30% marrow blasts indicates progression to AML. FAB classification is exclusively morphological: broadly patients with RA and RARS carry a much more favourable prognosis than those with RAEB and RAEB-t. Progression to AML or death from marrow failure related complications occurs much earlier in these latter groups with median survival generally <12 months. CMML has much more varied prognosis. Presenting Hb, neutrophil and platelets counts, as well as cytogenetic findings within each FAB subgroup provide the most helpful prognostic data for the individual patient. |
||
| top |