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Leukemia Research xxx (2009) xxxxxx

Contents lists available at ScienceDirect

Leukemia Research
journal homepage: www.elsevier.com/locate/leukres

Editorial

From FAB to 2008 WHO classication: The wide heterogeneity of refractory

anemia subtype among different countries

Myelodysplastic syndromes (MDS) are a heterogeneous group

of clonal diseases of the hemopoietic stem cell characterized by
ineffective hematopoiesis, peripheral cytopenias and variable risk
of transformation to acute leukemia (AML) [1]. In 1982, the FrenchAmerican-British (FAB) group introduced a classication system
for MDS based on morphologic criteria. FAB-MDS classication has
been extensively applied for more than two decades showing a
prognostic value, even if different survivals and risks of leukemic
transformation could be observed in patients within the same FAB
subtype [2]. In fact, about 15% of patients with refractory anemia
(RA) were shown to die for leukemic evolution even if RA was
described as a subset with favourable outcome [3,4].
In 1999, the rst WHO classication of MDS distinguished universus multilineage dysplasia among low grade MDS [5]. Refractory cytopenia with multilineage dysplasia (RCMD) was proposed
as a new MDS entity matching with FAB-RA/refractory anemia with
ringed sideroblasts (RARS) subtypes with more than 10% dysplastic
bone marrow cells in two or three hematopoietic cell lineages [5].
Soon after publication of WHO proposals, several groups debated
about the signicance of this classication: Greenberg et al. [6]
in 2000, highlighted two important issues not addressed by the
WHO proposals, such as the lack of minimum essential criteria
for dening MDS, and the lack of morphologic criteria for dening dysplastic involvement as needed for the diagnosis of RCMD
and RA. However, Germing et al. [7] showed a different prognosis
of patients with RA versus multilineage dysplasia in a retrospective examination of 1600 MDS patients. Furthermore, patients with
5q anomaly had a much better prognosis than other WHO subtypes, but this was only true for patients with a bone marrow
blast count below 5%. The same group of patients was followed
up to 2005, indicated that the differences in survival and rates of
leukemic evolution did not change in time [8]. In particular, the
different outcomes between unilineage and multilineage dysplasia in low risk MDS were conrmed in a prospective validation [8].
Biological and other clinical ndings also support the strength of
uni- or multilineage dysplasia as a classication criteria of MDS:
i.e. CD3 clonality or RAS mutation in RCMD as compared to RA
patients or peculiar response to erythropoietin or immunosuppressive agents in unilineage as compared to multilineage dysplasia
[9,10].
Several Eastern studies reported a lower incidence of RARS and
higher frequency of RA according to FAB classication, as compared
to Western countries [1113]. In 2005, Matsuda et al. [14] reported
that Japanese patients with RA have lower median age, more profound cytopenia, lower frequency of cytogenetic aberrations and

more favourable prognosis than German patients (in a large cohort

of 129 patients). However, the prognosis of Japanese RA patients
was more favourable than RCMD patients, with a lower cumulative
risk of leukemic evolution similar to what reported from German
group [6]. Nowadays such a clinical differences between Asian and
German RA patients did not allow the use of Western guidelines
and suggested to elaborate different clinical guidelines for Eastern
patients.
In 2008, the revised 2008 WHO classication of MDS conrmed
minimal morphologic criteria of MDS diagnosis: thus, at least 10%
of bone marrow cells of at least one hematopoietic cell lineage
must show unequivocal dysplasia to be considered as dysplastic
[15]. The novelty of the revised classication was the denition
of a more precise analysis of patients with unilineage dysplasia:
this category included MDS patients with less than 1% blasts in
the peripheral blood and less than 5% in the bone marrow, but
10% or more dysplastic cells in a single hematopoietic cell lineage. The new entity called refractory cytopenia with unilineage
dysplasia (RCUD), included three distinct subgroups of patients,
refractory anemia (RA) for those with anemia and dyserythropoiesis, refractory neutropenia (RN) for those with neutropenia and
isolated dysgranulopoiesis and refractory thrombocytopenia (RT)
for those with thrombocytopenia and morphologic dysplasia limited to the megakaryocytic lineage. The WHO criteria included also
patients with unilineage marrow dysplasia but with occasionally
bi-cytopenia: all patients with unilineage morphologic dysplasia
but with pancytopenia were classied as unclassiable MDS (MDSU).
The article by Matsuda et al. [16], published in this issue of
Leukemia Research, reported the differences of MDS subtype distribution between Japanese and German patients who received
RA diagnosis according to FAB classication and who were reclassied according to the 2008 WHO criteria. Starting from the
same database of the previous study [14], the new analysis showed
that the frequency of RCUD was higher in Japanese than in German
MDS patients, especially the comparison among RT category. Moreover, Japanese MDS patients have higher incidence of MDS-U and
low rates of RCMD than German patients. In accordance with other
studies [8,17], all patients with RCMD had shorter overall survival
(OS) and leukemic-free survival (LFS) than the other 2008 MDS subtypes, independently from the country of origin. The frequency of
del(5q) syndromes was lower in Japanese than in German group
of MDS patients. Differently from the previous report [14], similar
age was observed in Japanese and German MDS patients with RCUD
and MDS-U.

0145-2126/$ see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.leukres.2009.12.017

Please cite this article in press as: Breccia M. From FAB to 2008 WHO classication: The wide heterogeneity of refractory anemia subtype among
different countries. Leuk Res (2010), doi:10.1016/j.leukres.2009.12.017

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ARTICLE IN PRESS

Editorial / Leukemia Research xxx (2009) xxxxxx

The WHO 2008 re-denition of RA criteria support the authors

speculation of genetic rather than environmental factors underlying the clinical features of MDS FAB-RA groups in the two countries.
Conict of interest
The author stated no conict of interests.
Acknowledgement
No support for this work.
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Massimo Breccia
Department of Biotechnologies and Hematology,
University La Sapienza, Via Benevento 6,
00161 Rome, Italy
Tel.:

+39 06 857951; fax: +39 06 44241984.

E-mail address: breccia@bce.uniroma1.it
14 December 2009
Available online xxx

Please cite this article in press as: Breccia M. From FAB to 2008 WHO classication: The wide heterogeneity of refractory anemia subtype among
different countries. Leuk Res (2010), doi:10.1016/j.leukres.2009.12.017