H e m a t o lo g y E d u c a t io n - European Hematology Association

G. Garcia-Manero
Department of Leukemia,
University of Texas MD Anderson
Cancer Center, Houston, TX, USA
Hematology Education:
the education program for the
annual congress of the European
Hematology Association
2011;5:227-234
Myelodysplasic syndromes
Controversies in the treatment of myelodysplastic
syndromes
The myelodysplastic syndromes are a group of very complex myeloid disorders that more frequently
affect older individuals with comorbidities. Therapy for these patients is therefore complex and should
be tailored to both the characteristics of the disease, as well as potentially those of the patient. In
general, patients are stratified based on accepted standard criteria, such as International Prognostic
Scoring System (IPSS), into lower and higher risk groups. The goal of therapy in patients with lower
risk disease is to diminish transfusions requirements, improve quality of life, and potentially delay progression
to higher risk disease or acute myelogenous leukemia (AML). In higher risk disease, the goal
is to improve survival. A number of therapies are now widely available. These include growth factors,
iron chelation, immunosuppresion, lenalidomide, hypomethylating agents, AML-like therapies, and
allogeneic stem cell transplantation. In this review, I will try to integrate current knowledge on therapy
of MDS and discuss areas of controversy and potential future questions.
Introduction
Over the last decade we have witnessed a
revolution in our knowledge of the
myelodysplastic syndromes (MDS). 1 This has
resulted in the development of new morphological
classifications, 2 prognostic scores, 3-6 and
effective therapies. 7-9 More recently, we have
also witnessed the beginnings of the molecular
dissection of the disease. 10-13 The result has
been the realization that MDS encompasses a
more complex group of disorders than previously
anticipated. Indeed recent data from in
depth cytogenetic analysis indicate that the
level of complexity starts at the cytogenetic
level. 14 Furthermore, this group of diseases
affects a complex group of patients: the elderly.
15 These patients represent a particular challenge
due to the expected high incidence of
concomitant comorbidities and less tolerance
to intensive forms of therapy. Therefore,
treatment should be adapted to the subtype
of MDS, the expectations of survival and
transformation, specific molecular characteristics,
and the physical condition and age of
the patient. In this review, I do not plan to
provide an exhaustive summary of all treatments
available for MDS. Instead, I will try to
summarize my approach to the therapy of
MDS and highlight areas of controversy in
need of further research.
Current “standard of care” options
in myelodysplastic syndromes
In the paragraphs below, I provide a succinct
review with annotated references to
current standard therapies in MDS. This
topic was extensively reviewed recently 16
A B S T R A C T
and a proposed algorithm for the therapy of
MDS provided (Figure 1). 16
Current options for patients with lower risk disease
Patients with lower risk disease are those
with a low percentage of blasts and normal
or intermediate cytogenetics. 3 The degree of
transfusion requirements can vary significantly
in this subset of patients from none to
extensive weekly needs. This has a significant
effect on the survival and expectation
for the patient. 6,17 Traditionally, patients with
lower risk disease have been considered to
constitute a group with smoldering disease
and relative good prognosis. An analysis by
our group of survival in this patient category
indicated that survival in lower risk disease
can vary significantly and that a significant
fraction of patients have dismal prognosis
without intervention.(6) Furthermore, we
identified the cause of death in these
patients as primarily related to the disease
and not to disease progression to acute
myelogenous leukemia (AML) or due to
other comorbidities. 18 These two facts are
fundamental for our conceptualization of the
disease: they imply the potential need for
early therapeutic intervention in patients
with lower risk disease but anticipated poor
prognosis. This will have to be tested in
prospective clinical trials.
At the present time, a number of therapies
are widely used in patients with lower risk
MDS. Probably the most commonly used
front line therapy in lower risk MDS are
growth factors. Erythroid growth factors,
alone or in combination with myeloid
growth factors, are commonly used for
patients with anemia. 19 A number of predictive
models for response have been devel-
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 227 |