WHO, World Health Organization; MDS, myelodysplastic syndromes; PB, peripheral blood; BM, bone marrow; RS, ring sideroblasts
a Cytopenias MDS‐defining: Hb<100g/L, PLT<100×109/L, ANC<1.8×109/L; absolute monocytes count<1.0×109/L;
b with SF3B1 mutation;
c 1% PB blasts must be recorded on at least two separate observations;
d If with ≥15% ring sideroblasts and significant erythroid dysplasia, and are classified as MDS‐RS‐SLD.
Table 26.4 Differential diagnosis of clonal or idiopathic cytopenias and myelodysplastic syndromes.
Source: Adapted from Montalban‐Bravo et al.60
| Features | CHIP | ICUS | CCUS | MDS |
|---|---|---|---|---|
| Cytopenias | No | Yes (1 or more) | Yes (1 or more) | Yes (1 or more) |
| Dysplasia | No | None or minimal (non‐diagnostic for MDS) | None or minimal (non‐diagnostic for MDS) | Yes (>10% of elements per lineage in at least one |
| Somatic mutations | Yes, at a variant allele frequency ≥2%. Most commonly: DNMT3A, TET2, ASXL1, SRSF2, TP53 | No | Up to 36% overall with similar mutation VAF compared to MDS17% of ICUS without dysplasia45% of ICUS with some dysplasia | Up to 85% of patients |
| Risk of progression | Very low (0.5–1% per year) outside of therapy‐related setting | Up to 10% at five years | Up to 80% at five years but determined by mutational patterns |
CHIP, clonal hematopoiesis of indeterminate potential; ICUS, idiopathic cytopenia of undetermined significance; CCUS, clonal cytopenia of undetermined significance; MDS, myelodysplastic syndromes.
For MDS with ring sideroblasts, since the presence of the SF3B1 mutation is associated with the presence of RS, the updated WHO classification of MDS‐RS includes patients who have the SF3B1 mutation but lack excess blasts or an isolated del(5q) abnormality.
MDS with excess blasts is separated into patients with <10% marrow blasts (MDS‐EB‐1) and those with 10–19% marrow blasts (MDS‐EB‐2). It should also be noted that the denominator used for determining blast percentage in all myeloid neoplasms was redefined to include all nucleated bone marrow cells as opposed to only nonerythroid cells. This modification shifted a select group of patients previously categorized as AML to MDS‐EB.
MDS‐U (unclassifiable) is defined as the presence of 1% blasts in the peripheral blood, recorded on at least two separate occasions, with <5% BM blasts. MDS‐U also includes cases with single‐lineage dysplasia or isolated del(5q) and pancytopenia, or defining cytogenetic abnormality and one to three lineages cytopenia.
Uncertain conditions
Clonal somatic mutations involving MDS‐associated genes are detectable in individuals who otherwise do not meet the criteria for a definitive diagnosis of MDS or other myeloid neoplasms46 (Table 26.4). These mutations can be associated or not with cytopenias, and they can be associated with an increased risk of development of hematologic malignancies.45 The presence of such mutations without cytopenias or dysplasia has been called clonal hematopoiesis of indeterminate potential (CHIP) and is completely asymptomatic; cytopenia is associated with clonality in the absence of morphologic features of MDS is called clonal cytopenia of undetermined significance (CCUS).
Some patients may have persistent unexplained cytopenias with no or minimal dysplasia (non‐diagnostic for MSD), and this condition is called idiopathic cytopenia of undetermined significance (ICUS). In these conditions, regular monitoring is recommended at least every six months after the initial evaluation.59
Table 26.5 International Prognosis Scoring System (IPSS) for MDS.
Source: Adapted from Greenberg et al.6
| BM blasts (%) | Karyotypea | Cytopeniasb | Score |
|---|---|---|---|
| <5 | Good | 0 or 1 | 0 |
| 5–10 | Intermediate | 2 or3 | 0.5 |
| Poor | 1.0 | ||
| 11–20 | 1.5 | ||
| 21–30 | 2.0 |
a Karyotype definitions: good, –Y, –5q, –20q, normal; poor, chromosome 7 abnormalities or complex karyotypes (three or more abnormalities); intermediate, all others.
b Cytopenia definitions: haemoglobin, <10 g dl−1; absolute neutrophil count, <1800 μl−1; platelet count, <100,000 μl−1.
Prognosis
Several prognostic systems have been devised to better predict the outcome of individual patients. The IPSS6 has been in place since 1997. The prognostic score includes the percentage of blasts and number of cytopenias and cytogenetics6 (Tables 26.5 and 26.6). Favourable cytogenetics includes the loss of the Y, 5q, or 20q chromosomes or the presence of a normal karyotype. Adverse cytogenetic changes were those with three or more cytogenetic abnormalities or any abnormalities involving chromosome 7. Number scores are attributed