Grades are shown as the source states them. The WHO classification defines and classifies disease types; it does not grade evidence or make treatment recommendations, so no grades are shown.
Key recommendations
Myelodysplastic syndromes are renamed myelodysplastic neoplasms (still abbreviated MDS), to stress that they are neoplasms: clonal disorders of blood-forming cells defined by cytopenias and morphological dysplasia.
Myelodysplastic neoplasms: New terminology and grouping framework
Cytopenia thresholds, the same for MDS, clonal cytopenia and MDS/MPN: haemoglobin under 13 g/dL in men or under 12 g/dL in women; absolute neutrophil count under 1.8 × 10⁹/L; platelets under 150 × 10⁹/L.
Clonal haematopoiesis
Dysplasia counts as significant when it affects at least 10% of cells, in every lineage.
New terminology and grouping framework
MDS types fall into two groups: those with defining genetic abnormalities (MDS-5q, MDS-SF3B1 and MDS with biallelic TP53 inactivation) and those defined by morphology (MDS with low blasts, hypoplastic MDS, MDS with increased blasts and MDS with fibrosis).
New terminology and grouping framework; Table 3
A blast count of 20% or more in blood or marrow still defines AML rather than MDS. MDS with increased blasts 2 may nonetheless be treated as equivalent to AML for treatment decisions and clinical trials.
The boundary between MDS and AML is softened, but the 20% blast cutoff to define AML is retained
Risk is no longer built into the MDS types (blast count, ring sideroblasts, number of dysplastic lineages); prognosis is assessed with a dedicated scheme such as the Revised International Prognostic Scoring System (IPSS-R).
New terminology and grouping framework
Diagnosis
MDS with low blasts and isolated 5q deletion (MDS-5q): blasts under 5% in marrow and under 2% in blood, with a 5q deletion alone or with one other abnormality that is not monosomy 7 or a 7q deletion. Its criteria are unchanged, and an SF3B1 mutation or a single TP53 mutation does not override the diagnosis.
Table 3; MDS with defining genetic abnormalities
MDS with low blasts and SF3B1 mutation (MDS-SF3B1): no 5q deletion, monosomy 7 or complex karyotype. It includes over 90% of MDS with 5% or more ring sideroblasts; when SF3B1 is not mutated, 15% or more ring sideroblasts can substitute ("MDS with low blasts and ring sideroblasts").
Table 3; MDS with defining genetic abnormalities
MDS with biallelic TP53 inactivation (MDS-biTP53): under 20% blasts, with two or more TP53 mutations, or one with loss of the other allele. Over 90% have a complex karyotype, so they are very high risk on IPSS-R; this type takes precedence over MDS-5q and MDS-SF3B1 and may be regarded as equivalent to AML for treatment.
Table 3; MDS with defining genetic abnormalities
MDS with low blasts (MDS-LB): under 5% blasts in marrow and under 2% in blood. Recording whether one or several lineages are dysplastic is now optional, and the category "MDS, unclassifiable" has been removed.
Table 3; MDS, morphologically defined
MDS with increased blasts: MDS-IB1 has 5–9% blasts in marrow or 2–4% in blood; MDS-IB2 has 10–19% in marrow, 5–19% in blood, or Auer rods. MDS with fibrosis (MDS-f) has 5–19% blasts in marrow and 2–19% in blood.
Table 3
Hypoplastic MDS (MDS-h; marrow cellularity 25% or less, adjusted for age) is now a distinct type. It involves a T-cell attack on blood stem cells, overlaps with aplastic anaemia and paroxysmal nocturnal haemoglobinuria, and often responds to anti-thymocyte globulin. Diagnosis needs careful morphology, usually with a trephine biopsy, and testing for mutations or clonal chromosome abnormalities.
Table 3; MDS, morphologically defined
Clonal haematopoiesis of indeterminate potential (CHIP): a somatic mutation in a myeloid-cancer-associated gene at a variant allele fraction of 2% or more (4% for X-linked genes in men), in someone with no blood disorder and no unexplained cytopenia.
Clonal haematopoiesis
Clonal cytopenia of undetermined significance (CCUS): CHIP with one or more persistent cytopenias not explained by another condition, and not meeting the criteria for a myeloid neoplasm such as MDS.
Clonal haematopoiesis
Chronic myelomonocytic leukaemia (CMML), the commonest MDS/MPN overlap, needs persistent blood monocytosis of at least 0.5 × 10⁹/L and at least 10% of white cells, with under 20% blasts. When monocytes are between 0.5 and 1.0 × 10⁹/L, dysplasia and a clonal cytogenetic or molecular abnormality are both required.
Chronic myelomonocytic leukaemia; Table 6
CMML is myelodysplastic when the white count is under 13 × 10⁹/L and myeloproliferative at 13 × 10⁹/L or more; CMML-1 has under 5% blasts and promonocytes in blood and under 10% in marrow, and CMML-2 has 5–19% in blood and 10–19% in marrow.
Table 6
Investigations
Classification combines morphology (blood film, marrow aspirate and trephine), immunophenotyping, cytogenetics and molecular testing. Where detailed genetic testing is not available, the hierarchy allows classification at a broader family level.
Introduction
Finding biallelic TP53 inactivation needs sequencing that covers at least exons 4 to 11, usually with a copy-number test such as FISH for the TP53 locus (17p13.1) or an array.
MDS with defining genetic abnormalities
Treatment
Not covered in this summary — see the original guideline.
Important geriatric considerations
Clonal haematopoiesis becomes more common with age, and is associated with higher overall mortality, cardiovascular disease and myeloid cancers.
Clonal haematopoiesis
Myeloid neoplasms after chemotherapy or large-field radiotherapy for another condition ("post cytotoxic therapy") are becoming more common as cancer survival lengthens; most carry TP53 mutations. PARP inhibitors now count as a qualifying exposure, and methotrexate no longer does.
Secondary myeloid neoplasms; Myeloid neoplasms post cytotoxic therapy
Some MDS arises from an inherited predisposition (for example germline DDX41, RUNX1 or GATA2 variants). Genetic counselling and a family history are expected parts of the evaluation.
Myeloid neoplasms associated with germline predisposition; Table 10
Drug doses
Not covered in this summary — see the original guideline.
When to refer
Not covered in this summary — see the original guideline.
Red flags
Blasts reaching 20% or more mean transformation to AML, classified as AML, myelodysplasia-related.
AML, myelodysplasia-related
Recent updates
Changes in the 2022 edition: MDS with biallelic TP53 inactivation and hypoplastic MDS added as types; the terms "low blasts" and "increased blasts" introduced; CHIP and CCUS formally defined; "MDS, unclassifiable" removed; and the absolute monocyte threshold for CMML lowered from 1.0 to 0.5 × 10⁹/L.
Summary boxes; Chronic myelomonocytic leukaemia