Volumen: 12 # Number : 3
Publication Date : Septiembre - Diciembre Year: 2008
Authors: Mario Cazzola
Abstract: Myelodysplastic syndromes are clonal disorders
of hematopoietic stem cells with a propensity to
evolve into acute myeloid leukemia. The World
Health Organization (WHO) classification of myeloid
neoplasms is a very useful tool for defining the different
subtypes of these disorders. The WHO variants
show impressive clinical heterogeneity, ranging from
conditions with a near-normal standardized mortality
ratio to entities that are very close to acute myeloid
leukemia. Retrospective [Malcovati et al, J Clin
Oncol. 2005 Oct 20; 23 (30): 7594-603] and prospective
[Germing et al, Haematologica. 2006 Dec; 91 (12):
1596-604] studies have shown that the WHO classification
is feasible, provides valuable prognostic information,
and is useful for clinical decision making.
One of the novel WHO variants, the myelodysplastic
syndrome with isolated del(5q), has been found to
have a peculiar molecular basis (haploinsufficiency
of genes located at 5q31-q32) and a remarkable response
to lenalidomide. After showing that dependency
on transfusions has an effect on the likelihood
of survival [Cazzola & Malcovati, N Engl J Med. 2005
Feb 10; 352 (6): 536-8], we studied the most significant
prognostic factors in myelodysplastic syndromes
taking into account both their values at clinical onset
and their changes in time, with the aim of developing
a dynamic model for predicting survival and
leukemic evolution that can be applied at any time
during the course of the disease [Malcovati et al, J
Clin Oncol. 2007 Aug 10; 25 (23): 3503-10]. The most
important variables for the prognostic model were
WHO subgroups, karyotype, and transfusion requirement,
and based on these parameters we defined
a WHO classification-based prognostic scoring
system (WPSS). In the learning Pavia cohort, WPSS
was able to classify patients into five risk groups showing different survivals (median survival from
12 to 103 months) and probabilities of leukemic evolution.
WPSS was shown to predict survival and
leukemia progression at any time during follow-up,
and its prognostic value was confirmed in the
Duesseldorf validation cohort. More recently we
found that bone marrow fibrosis represents an additional
independent prognostic factor, as this feature
identifies a distinct clinical entity characterized
by high transfusion need and poor prognosis. A
risk-adapted treatment strategy is mandatory for
disorders that range from indolent conditions lasting
years to forms approaching acute myeloid leukemia.
The approach to a patient with myelodysplastic
syndrome should begin with a period of observation
to assess the rate of progression, if any.
Patients at very low risk of leukemic evolution and
without any transfusion requirement can just be
followed. At present, the only treatment that can
definitely prolong survival is allogeneic hematopoietic
stem-cell transplantation, but only a minority of
patients with myelodysplastic syndrome are eligible
for such treatment and have a donor. According to
a decision analysis [Blood. 2004 Jul 15; 104 (2): 579-
85] transplantation should be delayed in low risk
patients, while it should be performed soon in individuals
at high risk of leukemic progression. The remaining
potentially effective treatments include
erythropoietin alone or in combination with granulocyte
colony-stimulating factor, lenalidomide, immunosuppression
with antithymocyte globulin and/or
cyclosporine, hypomethylating agents (azacitidine
and decitabine), and intensive chemotherapy. Despite
recent progress, red-cell transfusions and iron chelation
remain the mainstays of therapy in many patients
with myelodysplastic syndrome.
Key words:
Pages : 75
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