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different countries. Leuk Res (2010), doi:10.1016/j.leukres.2009.12.017

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Leukemia Research xxx (2009) xxxxxx

Contents lists available atScienceDirect

Leukemia Research

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / l e u k r e s

Editorial

From FAB to 2008 WHO classification: 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 French-

American-British (FAB) group introduced a classification system

for MDS based on morphologic criteria. FAB-MDS classification 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 first WHO classification of MDS distinguished uni-

versus multilineage dysplasia among low grade MDS[5]. Refrac-

tory cytopenia with multilineage dysplasia (RCMD) was proposed

as a newMDS entitymatching with FAB-RA/refractory anemiawith

ringedsideroblasts (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 significance of this classification: 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 defining MDS, and the lack of morphologic criteria for defin-

ing 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 retrospec-

tive examination of 1600MDS patients. Furthermore, patients with

5qanomaly had a much better prognosis than other WHO sub-

types, 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 dyspla-

sia in low risk MDS were confirmed in a prospective validation[8].Biological and other clinical findings also support the strength of

uni- or multilineage dysplasia as a classification criteria of MDS:

i.e. CD3 clonality or RAS mutation in RCMD as compared to RA

patients or peculiar response to erythropoietinor immunosuppres-

sive agents in unilineage as compared to multilineage dysplasia

[9,10].

Several Eastern studies reported a lower incidence of RARS and

higherfrequency of RA accordingto FABclassification,as compared

to Western countries [1113]. In 2005, Matsuda et al. [14] reported

that Japanese patients with RA have lower median age, more pro-

found 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 classification of MDS confirmed

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 classification was the definition

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 lin-

eage. The new entity called refractory cytopenia with unilineage

dysplasia (RCUD), included three distinct subgroups of patients,

refractory anemia (RA) for those with anemia and dyserythro-

poiesis, refractoryneutropenia (RN) for thosewith neutropenia and

isolated dysgranulopoiesis and refractory thrombocytopenia (RT)

for those with thrombocytopenia and morphologic dysplasia lim-

ited 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

butwith pancytopeniawere classifiedas unclassifiable MDS (MDS-

U).

The article by Matsuda et al. [16], published in this issue of

Leukemia Research, reported the differences of MDS subtype dis-

tribution between Japanese and German patients who received

RA diagnosis according to FAB classification and who were re-

classified according to the 2008 WHO criteria. Starting from the

same database of the previous study [14], the new analysis showedthat the frequency of RCUD was higher in Japanese than in German

MDS patients,especiallythe comparisonamong RT category.More-

over, 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) andleukemic-free survival (LFS) than theother2008MDS sub-

types, 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

agewas observed in Japanese andGerman MDSpatients with RCUD

and MDS-U.

0145-2126/$ see front matter 2009 Elsevier Ltd. All rights reserved.

doi:10.1016/j.leukres.2009.12.017

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8/9/2019 anemie rfractaire

2/2

Please cite this article in press as: Breccia M. From FAB to 2008 WHO classification: The wide heterogeneity of refractory anemiasubtype among

different countries. Leuk Res (2010), doi:10.1016/j.leukres.2009.12.017

ARTICLE IN PRESSGModel

LR-3737; No.of Pages2

2 Editorial / Leukemia Researchxxx (2009) xxxxxx

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

speculation of genetic rather than environmental factors underly-

ingthe clinical features of MDSFAB-RA groupsin thetwo countries.

Conflict of interest

The author stated no conflict of interests.

Acknowledgement

No support for this work.

References

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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

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