Myelodysplastic Syndromes Staging 

Updated: Dec 31, 2015
  • Author: Matthew C Foster, MD; Chief Editor: Emmanuel C Besa, MD  more...
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WHO Classification and IPSS of Myelodysplastic Syndromes

The 2008 World Health Organization (WHO) classification of myelodysplastic syndromes (MDS), [1] as well as the International Prognostic Scoring System (IPSS), are provided below. [2]

Myelodysplastic syndromes are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis that present clinically as cytopenia(s), dysplasia in one or more hematopoietic cell lines in the bone marrow, and risk of transformation to acute myeloid leukemia (AML). [3]

See Myelodysplastic Syndromes: Classification, Features, Diagnosis, and Treatment Options, a Critical Images slideshow, to help identify, classify, work up, and treat these disorders.

Evidence of clonality may support the diagnosis of MDS and may manifest as an increase in bone marrow myeloblasts or recurrent cytogenetic abnormalities, although these findings are not necessary to fulfill the diagnostic criteria.

Myelodysplastic syndromes appear to represent several molecularly unique entities whose variation makes constructing a concise and practical framework difficult.

2008 WHO classification of MDS

The WHO classification system of MDS relies on incorporating clinical features, peripheral blood and bone marrow findings, and cytogenetic analysis. [1] This classification also includes a collection of heterogeneous neoplasms that share features of MDS and myeloproliferative neoplasms.

These "overlap syndromes" fall under the classification "myelodysplastic/myeloproliferative neoplasms" (MDS/MPN) and include the following:

  • Chronic myelomonocytic leukemia (CMML-1 and CMML-2)
  • Atypical chronic myeloid leukemia (CML), Bcr-Abl1 negative
  • Juvenile myelomonocytic leukemia (JMML)
  • MDS/MPN, unclassifiable

Although a detailed discussion of the overlap disorders is beyond the scope of this review, they share clinical, pathologic, and therapeutic features with MDS and can be treated similarly when they present with more features of MDS than MPN.

Refractory cytopenia with unilineage dysplasia (RCUD):

  • Blood: single cytopenia or bicytopenia
  • Bone marrow: dysplasia in ≥10% of one cell line, <5% blasts

Refractory anemia with ring sideroblasts (RARS):

  • Blood: anemia, no blasts
  • Bone marrow: ≥15% of erythroid precursors with ring sideroblasts, erythroid dysplasia only, <5% blasts

Refractory cytopenia with multilineage dysplasia (RCMD):

  • Blood: cytopenia(s), <1 × 10 9/L monocytes
  • Bone marrow: dysplasia in ≥10% of cells in ≥2 hematopoietic lineages, ±15% ring sideroblasts, <5% blasts

Refractory anemia with excess blasts-1 (RAEB-1):

  • Blood: cytopenia(s) ≥2-4% blasts, <1 × 10 9/L monocytes
  • Bone marrow: unilineage or multilineage dysplasia, no Auer rods, 5-9% blasts

Refractory anemia with excess blasts-2 (RAEB-2):

  • Blood: cytopenia(s), 5-19% blasts, <1 × 10 9/L monocytes
  • Bone marrow: unilineage or multilineage dysplasia, Auer rods, ±10-19% blasts

Myelodysplastic syndrome – unclassified (MDS-U):

  • Blood: cytopenias
  • Bone marrow: unilineage dysplasia or no dysplasia but characteristic MDS cytogenetics, <5% blasts

MDS associated with isolated del(5q):

  • Blood: anemia, platelet levels normal or increased
  • Bone marrow: unilineage erythroid dysplasia, isolated del(5q), <5% blasts

Therapy-related MDS (t-MDS):

  • Blood and bone marrow findings of one of the above diagnostic categories (frequently with multilineage dysplasia)
  • Previous history of exposure to cytotoxic chemotherapy and/or radiation therapy administered for treatment of cancer or nonneoplastic disease
  • 2008 WHO terminology: therapy-related myeloid neoplasm

IPSS and Revised IPSS (IPSS-R)

Although several prognostic scoring systems have been developed, [4, 5] the most widely used has been the IPSS. [2] The IPSS-R is a recdent revision of the IPSS that refines cytogenetic prognostic categorization and weights the prognostic score according to the severity of cytopenias in addition to the bone marrow blast percentage. The sum of the assigned points yields a prognostic score, which defines survival and risk of progression to AML. In addition to the clinical and pathologic variables included in the IPSS-R, point mutations in genes such as TP53, EZH2, ETV6, RUNX1, and ASXL1 have been shown to identify patients at risk for shortened survival or transformation to acute leukemia. [6] See the tables below.

Table 1. IPSS-R assignment of score (Open Table in a new window)

  Score Value
Prognostic variable 0 0.5 1 1.5 2 3 4
Marrow blasts (%) <2 - 2 - < 5 - 5-10 >10 -
Karyotype Very Good - Good Intermediate Poor Very Poor
Hemoglobin (g/dL) ≥10 - 8 - < 10 < 8 - - -
Absolute Neutrophil Count (x 109/L) ≥0.8 <0.8 - - - - -
Platelet Count (x 109/L) ≥100 50 - <100 <50 - - - -
Very Good Karyotype: del(11q), -Y; Good karyotype: 46XX, 46XY, del(5q), del(20q); poor karyotype: complex (≥3 unrelated abnormalities) or chromosome 7 abnormalities; intermediate karyotype: karyotypes not defined as good or poor.    

 

Table 2. IPSS-R risk groups, by sum of score [7] (Open Table in a new window)

Risk Category



(% IPSS-R population)



Overall Score Median Survival (years) Time for 25% of patients to progress to AML
Very Low (19) ≤1.5 8.8 Not reached
Low (38) 2-3 5.3 10.8
Intermediate (20) 3.5-4.5 3.0 3.2
High (13) 5-6 1.6 1.4
Very High (10) >6 0.8 0.73
AML = acute myeloid leukemia; IPSS-R = Revised International Prognostic Scoring System.