A new disease categorization of low-grade myelodysplastic syndromes based on the expression of cytopenia and dysplasia in one versus more than one lineage improves on the WHO classification

Abstract

Multilineage dysplasia was advanced by the World Health Organization to increase prognostic accuracy in myelodysplastic syndromes (MDS) classification. We performed a structured cytomorphological examination of bone marrow (BM) in 221 low-grade MDS patients, this in conjunction with strict guidelines for cytopenias. A dysplasia scoring system was developed utilizing dysplastic changes, which were associated with worse outcome on univariate and multivariate analysis corrected for the International Prognostic Scoring System (IPSS). Dysplasia X10% in one BM lineage and one cytopenia constituted the low-risk category UCUD or Unilineage Cytopenia and Unilineage Dysplasia. The high-risk category comprised patients with cytopenia in X2 lineages and dysplasia in X2 BM lineages, namely MCMD or Multilineage Cytopenia and Multilineage Dysplasia. Intermediate-risk patients had one cytopenia and multilineage dysplasia, or cytopenia in X2 lineages and unilineage BM dysplasia, designated UCMD/MCUD or Unilineage Cytopenia and Multilineage Dysplasia/Multilineage Cytopenia and Unilineage Dysplasia. This system utilizing cytopenia-dysplasia scoring at diagnosis enabled comprehensive categorization of low-grade MDS cases that predicted for overall as well as leukemia-free survival. Cytopenia-dysplasia categorization added additional prognostic values to the lower risk IPSS categories. This suggests that a standardized dysplasia scoring system, used in conjunction with cytopenia, could improve diagnostic and prognostic sub-categorization of MDS patients.

Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: A pilot study on a series of 56 patients

“…These included the overall number of CD34 þ cells, the presence of aberrant CD34 À /CD117 þ precursors, decreased numbers of CD34 À mature neutrophils and erythroid precursors, and increased numbers of CD36 À/lo NRBC. Thus, these variables could represent the prognostically most informative phenotypic parameters which would reflect accumulation of early altered hematopoietic precursors in association with an impaired production of both mature erythroid cells and neutrophils, which are well-established prognostic factors (42,43). In line with this, increasingly altered phenotypes (e.g., expression of lymphoid-associated markers) of immature myeloid precursors from RA and RCMD patients have also been associated with transfusion dependency and progression to advanced disease (20).…”

Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes

“…14 In addition, the effects of the validated IPSS variables (morphological bone marrow blast cell percentage, number of peripheral cytopenias and karyotype) within WHO categories have been shown to correlate with outcome in several studies. [15][16][17][18][19] A major limitation of the IPSS is that newly defined prognostic parameters have not been included, e.g. LDH, bone marrow fibrosis, circulating blasts (normal or aberrant), as well as data on transfusion requirements.…”

Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia

“…Our study included patients with NPM1 mutation and had a higher proportion of patients who underwent stem-cell transplant, which may explain our more restricted definition of morphologic dysplasia (micromegakaryocytes and hypogranulated myeloid cells) compared with the more broad definition encompassing all three lineages suggested in the study by Rozman et al 19 Our study also incorporated findings in bone marrow trephine biopsies, which are important in evaluating megakaryocytic dysplasia. 20 Mutational profiling has an increasing role in the risk stratification of acute myeloid leukemia, and specific mutations such as ASXL1 have been associated with morphologic dysplasia in acute myeloid leukemia. 26 Comprehensive mutational analysis may Morphologic dysplasia in acute myeloid leukemia define a biologically relevant group of myelodysplastic syndrome-related acute myeloid leukemia that is independent of morphologic dysplasia or myelodysplastic syndrome history.…”

“…19 Specific dysplastic features have shown strong correlation with a diagnosis of myelodysplastic syndrome compared with non-neoplastic processes, and certain specific dysplastic findings have also been associated with outcome in myelodysplastic syndrome patients. 20 In contrast, although the same dysplastic features are used to define both acute myeloid leukemia with myelodysplasia-related changes and myelodysplastic syndrome, the spectrum of dysplastic changes seen in acute myeloid leukemia is not well-documented. Neither the 50% dysplasia threshold nor the specific dysplastic features that should be counted have been validated with respect to association with clinical outcome in acute myeloid leukemia.…”