HAEM4Backup:Myelodysplastic Syndrome (MDS) with Excess Blasts

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Primary Author(s)

Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

Cancer Category/Type

Myelodysplastic Syndrome

Cancer Sub-Classification / Subtype

Myelodysplastic Syndrome with excess blasts (MDS-EB)

Definition / Description of Disease

Myelodysplastic syndrome (MDS) with excess blasts (EB) is a category of MDS characterized by <20% blasts in both peripheral blood and bone marrow. MDS-EB type 1 (MDS-EB-1) is classified as <5% blasts in the blood and <10% blasts in the bone marrow. MDS-EB type 2 (MDS-EB-2) is classified as 5-19% blasts in the blood and 10-19% blasts in the bone marrow with the presence of Auer rods[1][2]. The category of erythroid/myeloid-type acute erythroid leukemia in the 2008 WHO classification is now categorized as MDS-EB[3]. In addition, the majority of myelodysplastic syndrome with marrow fibrosis (MDS-F) belongs to myelodysplastic syndrome with excess blasts and fibrosis (MDS-EB-F)[4][5][6].

Synonyms / Terminology

Refractory anemia with excess blasts, erythroid/myeloid-type acute erythroid leukemia

Epidemiology / Prevalence

MDS-EB accounts for 40% of all cases of MDS (Arber DA, et al., (2016).)

  • Occurs mainly in patients aged greater than 50 years old

Clinical Features

The clinical features are often nonspecific and are generally related to the corresponding cytopenias such as anemia, thrombocytopenia and neutropenia. The recommended thresholds for cytopenia suggested by International Prognostic Scoring System (IPSS) (PMID: 22740453) include:

  • Hemoglobin concentration: <10 g/dL
  • Absolute neutrophil count: <1.8 x109/L AND
  • Platelet count: <100 x109/L

Sites of Involvement

Peripheral blood and bone marrow

Morphologic Features

The morphologic features of the peripheral blood and bone marrow are currently the gold standard for the diagnosis of MDS[3].

Categories Morphologic Features
Blood Abnormalities in all three myeloid cell lines; blasts commonly present
Bone marrow
  • Often hypercellular
  • Blasts aggregated
 Erythropoiesis: erythropoiesis increased, dyserythropoiesis: abnormally lobated nuclei, internuclear bridging
Granulopoiesis: dysplasia, nuclear hyposegmentation or hypersegmented nuclei or cytoplasmic hypogranularity
Dysmegakaryopoiesis: micromegakaryocytes often seen; multiple widely separated nuclei also can occur

Immunophenotype

Put your text here and/or fill in the table

Finding Marker
Positive (universal) CD34 and/or KIT (CD117), CD38, HLA-DR and CD13 and/or CD33
Positive (subset) CD7 (20%), CD56 (10%)

Chromosomal Rearrangements (Gene Fusions)

None

Characteristic Chromosomal Aberrations / Patterns

Gain of chromosome 8, del(5q) or t(5q), monosomy 7, del(7q), del(20q), complex karyotype

Genomic Gain/Loss/LOH

  • Nonspecific cytogenetic abnormalities have been observed in 30-50% of MDS-EB cases.
  • Gain of chromosome 8, del(5q) or t(5q), monosomy 7, del(7q), del(20q), complex karyotype[7].

Gene Mutations (SNV/INDEL)

Most frequent mutations: SRSF2, IDH1, IDH2, ASXL1, CBL, RUNX1, RAS

Other Mutations

None

Epigenomics (Methylation)

No

Genes and Main Pathways Involved

  • SRSF2: involved in pre-mRNA splicing
  • IDH1/IDH2: involved in hypoxia pathways
  • ASXL1: involved in chromatin remodeling
  • CBL: involved in targeting substrates for degradation by the proteasome
  • RUNX1: transcription factor for hematopoiesis cells
  • RAS: involved in RAS/MAPK pathway

Diagnostic Testing Methods

  • Quantification of dysplasia: Microscopy
  • Pathology: Immunophenotyping by flow cytometry
  • Genetics: Conventional karyotyping. Fluorescence in situ hybridization (FISH) analysis, microarray and sequencing

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • Diagnosis: 2-19% blasts in peripheral blood or 5-19% myeloblasts in bone marrow
  • Prognosis: Patients with MDS-EB-1 have a median survival of 16 months with 25% cases progressing to AML. While patients with MDS-EB-2 have a median survival of 9 months with 33% cases progressing to AML[8][9][10]. TP53, RUNX1 or ASXL1 mutations are associated with poor prognosis in MDS-EB with erythroid predominance[11][12].
  • Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the therapy of choice for MDS-EB in childhood with the best available donor[13]. Azacitidine, a DNA methyltransferase-inhibitor, has been reported to increase the overall survival for adult patients with high-risk MDS (MDS-REB) in comparison with conventional care[14].

Familial Forms

No

Other Information

No

Links

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References

  1. ↑ Greenberg, P.; et al. (1997-03-15). "International scoring system for evaluating prognosis in myelodysplastic syndromes". Blood. 89 (6): 2079–2088. ISSN 0006-4971. PMID 9058730.
  2. ↑ Germing, Ulrich; et al. (2006-01). "Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals". British Journal of Haematology. 132 (2): 162–167. doi:10.1111/j.1365-2141.2005.05853.x. ISSN 0007-1048. PMID 16398650. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.
  4. ↑ Lambertenghi-Deliliers, G.; et al. (1991-06). "Myelodysplastic syndrome with increased marrow fibrosis: a distinct clinico-pathological entity". British Journal of Haematology. 78 (2): 161–166. doi:10.1111/j.1365-2141.1991.tb04411.x. ISSN 0007-1048. PMID 1712222. Check date values in: |date= (help)
  5. ↑ Bae, E.; et al. (2013-12). "Differential diagnosis of myelofibrosis based on WHO 2008 criteria: acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis". International Journal of Laboratory Hematology. 35 (6): 629–636. doi:10.1111/ijlh.12101. ISSN 1751-553X. PMID 23693053. Check date values in: |date= (help)
  6. ↑ Orazi, Attilio (2007). "Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases". Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology. 74 (2): 97–114. doi:10.1159/000101709. ISSN 1015-2008. PMID 17587881.
  7. ↑ Germing, Ulrich; et al. (2006-12). "Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes". Haematologica. 91 (12): 1596–1604. ISSN 1592-8721. PMID 17145595. Check date values in: |date= (help)
  8. ↑ Germing, Ulrich; et al. (2006-12). "Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes". Haematologica. 91 (12): 1596–1604. ISSN 1592-8721. PMID 17145595. Check date values in: |date= (help)
  9. ↑ Strupp, Corinna; et al. (2003-05). "Refractory anemia with excess of blasts in transformation: analysis of reclassification according to the WHO proposals". Leukemia Research. 27 (5): 397–404. doi:10.1016/s0145-2126(02)00220-5. ISSN 0145-2126. PMID 12620291. Check date values in: |date= (help)
  10. ↑ Amin, H. M.; et al. (2005-09). "Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias". Leukemia. 19 (9): 1567–1572. doi:10.1038/sj.leu.2403876. ISSN 0887-6924. PMID 16049515. Check date values in: |date= (help)
  11. ↑ Grossmann, V.; et al. (2013-09). "Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics". Leukemia. 27 (9): 1940–1943. doi:10.1038/leu.2013.144. ISSN 1476-5551. PMID 23648669. Check date values in: |date= (help)
  12. ↑ Hasserjian, Robert P.; et al. (2010-03-11). "Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification". Blood. 115 (10): 1985–1992. doi:10.1182/blood-2009-09-243964. ISSN 1528-0020. PMC 2942006. PMID 20040759.
  13. ↑ Hasle, Henrik (2016-12-02). "Myelodysplastic and myeloproliferative disorders of childhood". Hematology. American Society of Hematology. Education Program. 2016 (1): 598–604. doi:10.1182/asheducation-2016.1.598. ISSN 1520-4383. PMC 6142519. PMID 27913534.
  14. ↑ Gore, Steven D.; et al. (2013-07). "A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial". Haematologica. 98 (7): 1067–1072. doi:10.3324/haematol.2012.074831. ISSN 1592-8721. PMC 3696610. PMID 23585522. Check date values in: |date= (help)

Notes

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