A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

Abstract

We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n > 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models, and performance was validated using 100 times fivefold cross-validation. Model stability was assessed by repeating its fit using different randomly chosen groups of 502 EUMDS cases. AUC was 0.96 (95% confidence interval, 0.95-0.97). MDS is predicted/excluded accurately in 86% of patients with unexplained anemia. A GBM score (range, 0-1) of less than 0.68 (GBM < 0.68) resulted in a negative predictive value of 0.94, that is, MDS was excluded. GBM ≥ 0.82 provided a positive predictive value of 0.88, that is, MDS. The diagnosis of the remaining patients (0.68 ≤ GBM < 0.82) is indeterminate. The discriminating variables: age, sex, hemoglobin, white blood cells, platelets, mean corpuscular volume, neutrophils, monocytes, glucose, and creatinine. A Web-based app was developed; physicians could use it to exclude or predict MDS noninvasively in most patients without a BM examination. Future work will add peripheral blood cytogenetics/genetics, EUMDS-based prospective validation, and prognostication.

Lymphoid aggregates in the bone marrow biopsies of patients with myelodysplastic syndromes – A potential prognostic marker?

“…On average, MDS/LA+ patients had approximately twice the incidence of past cancer and diabetes as compared to MDS/LA- patients, but only diabetes mellitus achieved statistical significance. The importance of this association remains to be clarified ( 27 ). There was a similar incidence of cardiovascular disease in both groups.…”

“…In our series, MDS patients with LA tended to have more baseline poor prognostic features, albeit without statistical significance. Of special interest is the association with diabetes, which should be studied further ( 27 ). While there are still more questions than answers, we hypothesize that this finding may reflect the role of the immune system in the pathogenesis of MDS.…”

Comparative diagnostic accuracy between simplified and original flow cytometric gating strategies for peripheral blood neutrophil myeloperoxidase expression in ruling out myelodysplastic syndromes

“…In contrast to other assays based on peripheral blood samples [8,9,[37][38][39][40], intra-individual RCV of neutrophil MPO expression has sufficient sensitivity and negative predictive value to safely rule out MDS on its own. Yet, the rate and extent of adoption of flow cytometric analysis for quantifying peripheral blood neutrophil MPO expression in patients with suspected MDS will be determined by issues of cost-effectiveness.…”

“…Although infrequent, procedure-related complications (hemorrhage and infection) may be associated with significant morbidity or even be lifethreatening [7]. In this context, a valid and reliable assay based on peripheral blood sample that accurately discriminates MDS from other cytopenia etiologies might exclude MDS without requiring invasive bone marrow aspiration [8,9].…”

High concordance of clone detection between peripheral blood and bone marrow by targeted next‐generation sequencing—A pilot study in patients with MDS

“…To improve this model authors suggest that peripheral cytogenetics and molecular genetics be included. 12 Mutation analyses from PB can also be performed with pre-enrichment of CD34 + cells from PB or using PB-derived cell-free DNA (cfDNA). 13,14 However, in both methods several technical difficulties or variable sensitivities can occur.…”