Blood, 15 April 2002, Vol. 99, No. 8, pp. 3074-3075
CORRESPONDENCE
To the editor:
Myelodysplastic syndromes: from French-American-British to
World Health Organization: a commentary
Nösslinger and coworkers1 are to be
complimented on a carefully conducted retrospective survival study of
431 patients with primary myelodysplastic syndromes (MDSs) comparing
the original French-American-British (FAB) proposals2 and
the recently published World Health Organization (WHO) proposal
classifications of MDS.3 However, we are concerned about
the authors' interpretation of the WHO criteria and the resulting
impact on their survival studies. The critical changes in the WHO
classification from the FAB include the following: (1) lowering the
blast percentage for the diagnosis of acute myeloid leukemia (AML) to
20% from 30%, thus eliminating refractory anemia with excess blasts
in transformation (RAEB-T); (2) moving dysplastic chronic
myelomonocytic leukemia (CMML) into a proposed new category of myeloid
disease with features overlapping myelodysplastic syndromes and
myeloproliferative disorders; (3) subdividing RAEB into 2 types: RAEB-1
(5%-9% marrow blasts) and RAEB-2 (10%-19% marrow blasts); and (4)
separating refractory anemia (RA) and refractory anemia with ringed
sideroblasts (RARS) into 2 broad categories based on the presence of
multilineage (2 or 3 myeloid cell lines) or unilineage (mainly
affecting the erythroid series) dysplasia.
Unfortunately the reference quoted3 for the WHO
classification did not provide sufficient information on the precise
criteria described in detail in the recently published WHO
manual,4 and, in addition, the authors do not
reference the Germing et al paper,5 which confirms these
new proposals. An additional review of the new WHO classification was
published before the final criteria of the precise percent of
dysplastic cells and the consideration of merging the dysplastic and
proliferative forms of CMML were agreed upon.6
The major difficulty we have with the Nösslinger et al study is
the adoption of the "50%" criteria for dysplasia in 2 or more cell
lines for refractory cytopenia with multilineage dysplasia (RCMD). In
the WHO proposals the threshold of 50% dysplasia has been utilized
only in identifying AML with multilineage dysplasia7 but
not for the MDS category of RCMD. In fact, in the WHO proposals RCMD is
defined as an MDS subgroup with fewer than 5% blasts in the bone
marrow, and dysplasia in 10% or more of the cells of 2 or more myeloid
lineages (erythroid, granulocytic, and/or megakaryocytic). These
criteria were adapted in the study of 1600 patients with MDS by Germing
et al,5 although they did elect to use a 40% threshold
for megakaryocytes. Germing et al and others8,9 have
confirmed the worse prognosis of RCMD compared to RA or RARS. To
accurately evaluate the WHO proposals it will be necessary to reassess
the "unclassified" group in the Nösslinger et al study
utilizing these criteria. It is very likely that the "unclassified" category (MDS-U) would diminish considerably, impacting the survival results.
In addition others have demonstrated that the survival of CMML is
dependent on the bone marrow blast percentage10 and that CMML is much more heterogeneous than other subtypes of MDS. In order to
emphasize the prognostic importance of the blast percentage in CMML the
WHO classification divides CMML into 2 categories, CMML-1 and CMML-2,
depending on the blast count in the peripheral blood and the bone
marrow. It does not subdivide CMML according to the white blood cell
count. In Table 1 of the Nösslinger et al
article,1 CMML resembles RAEB in the
International Prognostic Scoring System11 (IPSS)
distribution. The separation of RAEB into 2 types (5%-9% blasts and
10%-19% blasts) is of importance as the authors demonstrate with a
significant difference in IPPS distribution. A similar analysis of
their patients with CMML should be performed. Confirmation of the
similarities in outcome for RAEB-T and AML in the Nösslinger et
al study provides further evidence in support of allowing such patients
(20%-30% marrow blasts) to enter AML trials where appropriate.
In summary it is our hope that Nösslinger and colleagues will
consider reviewing their data using the recently published WHO
criteria. Such an effort would be important, because, although the
Nösslinger et al study is interesting, it does not justify any
statement about the validity of the WHO classification. We anticipate
that a new look at the data of Germing et al would confirm the
conclusion that the WHO system does provide improved and
relevant guidelines for the classification of patients with MDS.
John M. Bennett, Richard D. Brunning, and James W. Vardiman
Correspondence: John M. Bennett, James P. Wilmot Cancer Center,
University of Rochester Medical Center, 601 Elmwood Ave, Box 704, Rochester, NY 14642
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