hematology education - European Hematology Association

M. Cazzola
L. Malcovati
Department of Hematology
Oncology, University of Pavia
Medical School, Pavia, Italy
Hematology Education:
the education program
for the annual congress of the
European Hematology Association
2009;3:181-187
Myelodysplastic syndromes
Risk-adapted treatment of myelodysplastic syndromes
M yelodysplastic
syndromes (MDSs)
are usually characterized by clonal
proliferation of hematopoietic
cells, which partly retain their capacity to
differentiate and maturate, but do so in an
inefficient manner. 1 The bone marrow is
generally hypercellular while peripheral
blood cells are variably reduced (cytopenia),
and several morphological abnormalities
are observed in these two compartments.
2 In addition, clones of hematopoietic
cells carrying non-random cytogenetic
abnormalities are typically found in these
disorders. 3 With time, there is a progressive
impairment in the capacity of hematopoietic
cells to differentiate and maturate; blast
cells may appear in the bone marrow and
peripheral blood, and there is an increasingly
high risk of evolution to overt acute
myeloid leukemia (AML). The basic components
of the definition of MDS are clonality,
ineffective hematopoiesis and preleukemic
nature. These features, however,
A B S T R A C T
Myelodysplastic syndromes (MDS) are usually characterized by clonal proliferation of hematopoietic
cells, which partly retain their capacity to differentiate and maturate, but do so in an inefficient
manner. Their clinical heterogeneity is best illustrated by the observation that these disorders range
from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid
leukemia (AML). A risk-adapted treatment strategy is mandatory for conditions showing a so highly
variable clinical course, and definition of the individual risk has been based so far on the use of prognostic
scoring systems. We have developed a prognostic model that accounts for the WHO categories,
cytogenetics and transfusion dependency. This WHO classification-based prognostic scoring system
(WPSS) is able to classify patients into five risk groups showing different survivals and probabilities of
leukemic evolution. WPSS predicts survival and leukemia progression at any time during follow-up,
and may therefore be used for implementing risk-adapted treatment strategies. The approach to a
patient with myelodysplastic syndrome should always begin with a period of observation, with
sequential peripheral blood counts – and sometimes bone marrow examinations – to assess the rate
of progression, if any. Several therapeutic tools have been proposed in the last decades but only few
survived the evidence-based criteria of efficacy. Patients with very low WPSS risk do not need any
treatment and can be just followed regularly. Transfusion dependent patients with low WPSS risk can
be treated with recombinant human erythropoietin. Responsive patients are mainly those with early
disease, inadequate endogenous erythropoietin production and low need for blood transfusion.
Transfusion-dependent patients with myelodysplastic syndrome associated with del(5q) may respond
to lenalidomide with cytogenetic remission and abolishment of transfusion requirement. However, in
2008 the EMEA Committee for Medicinal Products for Human Use was of the opinion that the benefits
of lenalidomide in the treatment of anemia of MDS with del(5q) did not outweigh its potential
risks, and therefore the drug has not been approved for this use in Europe. A recent survival study comparing
azacitidine versus conventional care showed that treatment with azacitidine increases overall
survival in patients with higher-risk MDS. Thus, EMEA has recently approved azacitidine for the treatment
of adult patients with high-risk myelodysplastic syndrome who are not eligible for allogeneic
hematopoietic stem cell transplantation. The only treatment that can cure a patient with myelodysplastic
syndrome is still allogeneic stem cell transplantation. It can be estimated that approximately
one third of patients receiving an allogeneic transplantation are cured with this treatment, but only a
minority of all MDS patients are eligible and have a donor.
may be difficult to assess in a clinical setting,
and – as stated in the World Health
Organization (WHO) classification 4 –
MDSs remain among the most challenging
of the myeloid neoplasms for proper diagnosis
and classification.
Diagnosis and classification
MDSs were defined and classified in 1982
by the French American British (FAB)
group. 5 In 2001, the WHO classification of
myeloid neoplasms was developed. 6 This
classification has been updated recently, 7
and the 2008 WHO classification of myelodysplastic
syndromes/neoplasms is reported
in Table 1.
The current diagnostic approach includes
peripheral blood and bone marrow morphology
(to evaluate abnormalities of peripheral
blood cells and hematopoietic precursors),
bone marrow biopsy (to assess
marrow cellularity, fibrosis and topography),
and cytogenetics (to identify non-ran-
Hematology Education: the education program for the annual congress of the European Hematology Association | 2009; 3(1) | 181 |