Myelodysplastic syndrome classification
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Classification
French-American-British (FAB) classification
In 1974 and 1975 a group of pathologists from France, the United States, and Britain met and deliberated and derived the first widely used classification of these diseases. This French-American-British (FAB) classification was published in 1976 and revised in 1982. Cases were classified into 5 categories: (ICD-O codes are provided where available)
- (Template:ICDO) Refractory anemia (RA) - characterized by less than 5% primitive blood cells (myeloblasts) in the bone marrow and pathological abnormalities primarily seen in red cell precursors;
- (Template:ICDO) Refractory anemia with ringed sideroblasts (RARS) - also characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called "ringed sideroblasts";
- (Template:ICDO) Refractory anemia with excess blasts (RAEB) - characterized by 5-19% myeloblasts in the marrow;
- (Template:ICDO) Refractory anemia with excess blasts in transformation (RAEB-T) - characterized by 20-29% myeloblasts in the marrow (30% blasts is defined as acute myeloid leukemia);
- (Template:ICDO) Chronic myelomonocytic leukemia (CMML) - not to be confused with chronic myelogenous leukemia or CML - characterized by less than 20% myeloblasts in the bone marrow and greater than 1000 * 109/uL monocytes (a type of white blood cell) circulating in the peripheral blood.
A table comparing these is available from the Cleveland Clinic.
The best prognosis is seen with refractory anemia with ringed sideroblasts and refractory anemia, where some non-transplant patients live more than a decade (the average is on the order of 3-5 years, although long term remission is possible if a bone marrow transplant is successful); the worst outlook is with RAEB-T, where the mean life expectancy is less than 1 year. Leukemic transformation occurs in about 10-17% of patients with RA/RARS; it is approximately 40-60% for patients with RAEB. The others die of complications of low blood count or unrelated disease.
The FAB classification was used by pathologists and clinicians for almost 20 years. By the early 21st century the WHO classification had replaced it.
WHO classification
In the late 1990s a group of pathologists and clinicians working under the World Health Organization (WHO) modified this classification, introducing several new disease categories and eliminating others.
One new category was refractory cytopenia with multilineage dysplasia (RCMD), which includes patients with pathological changes not restricted to red cells (i.e., prominent white cell precursor and platelet precursor (megakaryocyte) dysplasia. See below for morphologic definitions of dysplasia.
The list of dysplastic syndromes under the new WHO system includes:
- Refractory anemia (RA)
- Refractory anemia with ringed sideroblasts (RARS)
- Refractory cytopenia with multilineage dysplasia (RCMD)
- Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)
- Refractory anemia with excess blasts I and II
- 5q- syndrome
- Myelodysplasia unclassifiable (seen in those cases of megakaryocyte dysplasia with fibrosis and others)
RAEB was divided into *RAEB-I (5-10% blasts) and RAEB-II (11-19%) blasts, which has a poorer prognosis than RAEB-I. Auer rods may be seen in RAEB-II which may be difficult to distinguish from acute myeloid leukemia. The presence of 20% or more blasts denotes the diagnosis of AML. (In the new WHO classification RAEB-T no longer exists).
5q- syndrome, typically seen in older women was added to the classification. The diagnosis of 5q minus syndrome requires that 5q minus MUST be an isolated abnormality. Clinical manifestations include a tendency towards a hypercellular bone marrow, macrocytosis/RA, normal or high platelet counts and hypolobulated megakaryocytes. It carries a good prognosis, with a median survival > 5 years, a low risk of AML and a benign course. 14(RPS4) is the underlying genetic defect of 5q minus syndrome. Haploinsufficiency of the ribosomal gene 14(RPS4)occurs here; it is required for the maturation of the 40s ribosomal subunit and it maps to the deleted region on 5q minus. 67% of patients with 5q minus achieve transfusion independence with the administration of Lenalidomide. Lenalidomide in 5q minus causes a response by decreasing Cdc25c and PP2A mRNA expression. Lenalidomide has such high clinical activity for this type of MDS that it is almost comparable to teh track record of imatinib in CML.
CMML was removed from the myelodysplastic syndromes and put in a new category of myelodysplastic-myeloproliferative overlap syndromes. Not all physicians concur with this reclassification. This is because the underlying pathology of the diseases is not well understood. It is difficult to classify things that are not well understood.