Summary
The estimation of survival of myelodysplastic syndromes (MDS) and risk of progression into acute myeloid leukaemia is challenging due to the heterogeneous clinical course. The most widely ...used prognostic scoring system (International Prognostic Scoring System IPSS) was recently revised (IPSS‐R). The aim of this study was to investigate the prognostic relevance of flow cytometry (FC) in the context of the IPSS‐R. Bone marrow aspirates were analysed by FC in 159 patients with MDS. A flow score was calculated by applying the flow cytometric scoring system (FCSS). Patients were assigned to IPSS and IPSS‐R risk groups. The FCSS correlated with the World Health Organization classification, IPSS and IPSS‐R risk groups. Mild flow cytometric abnormalities were associated with significantly better overall survival (OS) and lower risk of disease evolution. The presence of aberrant myeloid progenitors was associated with transfusion dependency and disease progression. Most importantly, the FCSS identified prognostic subgroups within the IPSS‐R cytogenetic good risk and low risk group. Flow cytometric analysis in patients with MDS provides additional prognostic information and is complementary to the IPSS‐R. The addition of a flow cytometric score next to the clinical parameters within the IPSS‐R is a further refinement of prognostication of patients with MDS.
Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the ...evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117
erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84-94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86-97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage.
Abstract Mandatory for the diagnosis of myelodysplastic syndromes (MDS) is the presence of dysplasia in >10% of cells within one or more cell lineages or presence of >15% ring sideroblasts or ...presence of MDS-associated cytogenetic (CG) abnormalities. Discrimination between neo-plastic and non-neoplastic causes of cytopenias can be challenging when dysplastic features by cytomorphology (CM) are minimal and CG abnormalities are absent or non-discriminating from other myeloid neoplastic disorders. This study evaluated a standard diagnostic approach in 379 patients with unexplained cytopenias and highlights the additional value of flow cytometry (FC) in patients with indeterminate CM and CG. CM reached no clear-cut diagnosis in 44% of the patients. Here, CG was able to identify two additional patients with MDS; other CG results did not reveal abnormalities or were not contributory. Based on the FC results, patients without a diagnosis by CM and CG were categorized ‘no MDS-related features’ (65%), ‘limited number of MDS-related changes’ (24%), and ‘consistent with MDS’ (11%). Patients were followed over time in an attempt to establish or confirm a diagnosis (median follow-up 391 d, range 20–1764). The specificity (true negative) of MDS-FC analysis calculated after follow-up was 95%. FC can aid as a valuable tool to exclude MDS when CM and additional CG are not conclusive in patients with cytopenia.
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•The Ki-67 proliferation index can be of help to diagnose (low-grade) MDS.•Integrating Ki-67 into the Ogata score increased its sensitivity for low-grade MDS.•The Ogata/Ki-67 scoring ...system includes assessment of the erythroid cell lineage.
Although flow cytometric detection of myelodysplastic syndrome (MDS) with the Ogata score has a high specificity, its sensitivity for low-grade MDS is low. Additional markers are needed to improve its diagnostic reliability. Therefore, we investigated the diagnostic performance of the Ki-67 proliferation index in bone marrow (BM) cell populations for detection of MDS.
BM aspirates from 50 MDS patients and 20 non-clonal cytopenic controls were analyzed with flow cytometry to determine the Ogata score and the Ki-67 proliferation indices in different cell populations.
Ki-67 proliferation indices alone could be used to detect MDS with a sensitivity of up to 80 % and specificity of up to 70 %. Combining the Ogata score with the Ki-67 proliferation index of erythroid cells significantly improved its sensitivity for detection of MDS from 66 % to 90 %, while maintaining a specificity of 100 %. Particularly, the sensitivity for detection of low-grade MDS improved from 56 % to 91 %.
This is the first study using Ki-67 proliferation indices to detect MDS and shows their particularly high diagnostic sensitivity for detection of low-grade MDS. Integration of the Ki-67 proliferation index of erythroid cells into the Ogata score significantly improved its sensitivity without loss of the high specificity.
Summary
Splicing factor 3B subunit 1 (SF3B1) mutations define a distinct myelodysplastic syndromes (MDS) patient group with a relatively favourable disease course and high response rates to ...luspatercept. Few data are available on bone marrow phenotype beyond ring sideroblasts in this subgroup of patients with MDS. In the present study, we identified immunophenotypic erythroid, myelomonocyte and progenitor features associated with SF3B1 mutations. In addition, we illustrate that SF3B1‐mutation type is associated with distinct immunophenotypic features, and show the impact of co‐occurrence of a SF3B1 mutation and a deletion of chromosome 5q on bone marrow immunophenotype. These genotype–phenotype associations and phenotypic subtypes within SF3B1‐MDS provide leads that may further refine prognostication and therapeutic strategies for this particular MDS subgroup.
Purpose The aim of the study is to report on the feasibility, reliability, validity, and the norm-references of the Dutch version of the PedsQL ™ Multidimensional Fatigue Scale. Methods The study ...participants are four hundred and ninetyseven parents of children aged 2-18 years and 366 children aged 5-18 years from various day care facilities, elementary schools, and a high school who completed the Dutch version of the PedsQL ™ Multidimensional Fatigue Scale. Results The number of missing items was minimal. All scales showed satisfactory internal consistency reliability, with Cronbach's coefficient alpha exceeding 0.70. Testretest reliability was good to excellent (ICCs 0.68-0.84) and inter-observer reliability varied from moderate to excellent (ICCs 0.56-0.93) for total scores. Parent/child concordance for total scores was poor to good (ICCs 0.25-0.68). The PedsQL ™ Multidimensional Fatigue Scale was able to distinguish between healthy children and children with an impaired health condition. Conclusions The Dutch version of the PedsQL ™ Multidimensional Fatigue Scale demonstrates an adequate feasibility, reliability, and validity in another sociocultural context. With the obtained norm-references, it can be utilized as a tool in the evaluation of fatigue in healthy and chronically ill children aged 2-18 years.
Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP‐based genomic array profiling is a high‐resolution tool that also enables ...genome wide analysis. We compared karyotyping with oligo/SNP‐based array profiling in 104 MDS patients from the HOVON‐89 study. Oligo/SNP‐array identified all cytogenetically defined genomic lesions, except for subclones in two cases and balanced translocations in three cases. Conversely, oligo/SNP‐based genomic array profiling had a higher success rate, showing 55 abnormal cases, while an abnormal karyotype was found in only 35 patients. In nine patients whose karyotyping was unsuccessful because of insufficient metaphases or failure, oligo/SNP‐based array analysis was successful. Based on cytogenetic visible abnormalities as identified by oligo/SNP‐based genomic array prognostic scores based on IPSS/‐R were assigned. These prognostic scores were identical to the IPSS/‐R scores as obtained with karyotyping in 95%‐96% of the patients. In addition to the detection of cytogenetically defined lesions, oligo/SNP‐based genomic profiling identified focal copy number abnormalities or regions of copy neutral loss of heterozygosity that were out of the scope of karyotyping and fluorescence in situ hybridization. Of interest, in 26 patients we demonstrated such cytogenetic invisible abnormalities. These abnormalities often involved regions that are recurrently affected in hematological malignancies, and may therefore be of clinical relevance. Our findings indicate that oligo/SNP‐based genomic array can be used to identify the vast majority of recurrent cytogenetic abnormalities in MDS. Furthermore, oligo/SNP‐based array profiling yields additional genetic abnormalities that may be of clinical importance.