TY - JOUR

T1 - ProGraME

T2 - A novel flow cytometry algorithm for the diagnosis of low-risk myelodysplastic syndromes in patients with cytopenia

AU - Therkelsen, Jesper

AU - Træden, Dicte Wilhjelm

AU - Schjødt, Ida

AU - Andersen, Mette Klarskov

AU - Sjö, Lene Dissing

AU - Hansen, Jakob Werner

AU - Grønbæk, Kirsten

AU - Dimopoulos, Konstantinos

N1 - Publisher Copyright: © 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - Objectives: Flow cytometry (FC) is, together with morphology, genetics, and cytogenetics, used in the diagnostic assessment of cytopenia, as its value in evaluating bone marrow dysplasia been highlighted by several studies. However, despite the development of algorithms and guidelines, there is still a lack of standardization of the FC assessment of bone marrow dysplasia. Methods: By combining FC, together with morphological analysis and cytogenetic/molecular assessment in a training cohort of 209 patients, we created a novel score, ProGraME, which includes four parameters, each from a different cell lineage (Progenitor cells, Granulocytes, Monocytes, Erythroid precursors), solely based on relevant population gating. Points for ProGraME were attained for: lymphoid precursors ≤5% of all CD34+ cells (1.5 point); a granulocyte-to-lymphocyte side-scatter ratio ≤6 (1 point); a monocyte CD33-CV% ≥ 63 (2 points), and an erythroid precursor CD36-CV% ≥ 65 (2 points). Results: Using a cutoff of ≥2 as suggestive of dysplasia, ProGraME showed a sensitivity of 91% and a specificity of 81% in the training cohort and 95% and 75%, respectively, in an independent validation cohort of 159 patients. In addition, ProGraME had a very high negative predictive value of 97.1% and 97.8% in the training and validation cohorts, respectively, offering a useful tool for excluding bone marrow dysplasia. Finally, among the 23 CCUS patients that scored positive for dysplasia with ProGraME in the training cohort, 16 of them (69%) carried high-risk mutations, suggesting that FC might help identify early changes of dysplasia. Conclusions: ProGraME can potentially optimize the FC diagnosis of low-risk myelodysplasia without minimal requirements of flow analysis other than accurate population gating.

AB - Objectives: Flow cytometry (FC) is, together with morphology, genetics, and cytogenetics, used in the diagnostic assessment of cytopenia, as its value in evaluating bone marrow dysplasia been highlighted by several studies. However, despite the development of algorithms and guidelines, there is still a lack of standardization of the FC assessment of bone marrow dysplasia. Methods: By combining FC, together with morphological analysis and cytogenetic/molecular assessment in a training cohort of 209 patients, we created a novel score, ProGraME, which includes four parameters, each from a different cell lineage (Progenitor cells, Granulocytes, Monocytes, Erythroid precursors), solely based on relevant population gating. Points for ProGraME were attained for: lymphoid precursors ≤5% of all CD34+ cells (1.5 point); a granulocyte-to-lymphocyte side-scatter ratio ≤6 (1 point); a monocyte CD33-CV% ≥ 63 (2 points), and an erythroid precursor CD36-CV% ≥ 65 (2 points). Results: Using a cutoff of ≥2 as suggestive of dysplasia, ProGraME showed a sensitivity of 91% and a specificity of 81% in the training cohort and 95% and 75%, respectively, in an independent validation cohort of 159 patients. In addition, ProGraME had a very high negative predictive value of 97.1% and 97.8% in the training and validation cohorts, respectively, offering a useful tool for excluding bone marrow dysplasia. Finally, among the 23 CCUS patients that scored positive for dysplasia with ProGraME in the training cohort, 16 of them (69%) carried high-risk mutations, suggesting that FC might help identify early changes of dysplasia. Conclusions: ProGraME can potentially optimize the FC diagnosis of low-risk myelodysplasia without minimal requirements of flow analysis other than accurate population gating.

KW - algorithm

KW - CCUS

KW - cytopenia

KW - diagnosis

KW - flow cytometry

KW - myelodysplasia

U2 - 10.1111/ejh.14086

DO - 10.1111/ejh.14086

M3 - Journal article

C2 - 37611916

AN - SCOPUS:85168689550

VL - 111

JO - Scandinavian Journal of Haematology

JF - Scandinavian Journal of Haematology

SN - 0902-4441

IS - 6

ER -