The challenging task of enumerating blasts in the bone marrow

TY - JOUR

T1 - The challenging task of enumerating blasts in the bone marrow

AU - Hodes, Aaron

AU - Calvo, Katherine R.

AU - Dulau, Alina

AU - Maric, Irina

AU - Sun, Junfeng

AU - Braylan, Raul

N1 - Publisher Copyright: © 2018 Elsevier Inc.

PY - 2019/1

Y1 - 2019/1

N2 - Enumeration of blasts in the bone marrow is critical for diagnostic, prognostic, and therapeutic response evaluation in myelodysplastic syndromes, myeloproliferative neoplasms and acute leukemias. However, few studies have examined the accuracy and precision of marrow blast counting using standard microscopic procedures. In our study, 4 experienced hematopathologists evaluated blast percentages in marrow using either differential counts on aspirate smears or visual estimates on CD34-stained trephine biopsies. Results of an independent observer's manual counts of individual labeled and unlabeled cells performed on high resolution digital images of CD34-stained trephine biopsies were designated as the “Digital Reference.” Hematopathologists’ blast counts showed excellent interobserver reproducibility, but the counts in smears and trephine biopsies correlated poorly with each other. Compared to the Digital Reference, both smear and trephine evaluations showed positive bias and high variability. The biopsy showed less variability but higher positive bias relative to the smears, indicating that counts were overestimated more in the hematopathologists’ biopsy evaluation. Flow cytometric counts correlated well with the Digital Reference, and cases with high blast count generally showed worse cytogenetic findings. Our results demonstrate the need for better counting methods if significant decisions are made based on microscopic enumeration of blasts. Further efforts should be made to develop markers to better define blast cells and perhaps incorporate automated digital imaging technologies to enumerate them. Also, consideration should be given to quantifying blasts per marrow area in biopsies instead of per nucleated cells.

AB - Enumeration of blasts in the bone marrow is critical for diagnostic, prognostic, and therapeutic response evaluation in myelodysplastic syndromes, myeloproliferative neoplasms and acute leukemias. However, few studies have examined the accuracy and precision of marrow blast counting using standard microscopic procedures. In our study, 4 experienced hematopathologists evaluated blast percentages in marrow using either differential counts on aspirate smears or visual estimates on CD34-stained trephine biopsies. Results of an independent observer's manual counts of individual labeled and unlabeled cells performed on high resolution digital images of CD34-stained trephine biopsies were designated as the “Digital Reference.” Hematopathologists’ blast counts showed excellent interobserver reproducibility, but the counts in smears and trephine biopsies correlated poorly with each other. Compared to the Digital Reference, both smear and trephine evaluations showed positive bias and high variability. The biopsy showed less variability but higher positive bias relative to the smears, indicating that counts were overestimated more in the hematopathologists’ biopsy evaluation. Flow cytometric counts correlated well with the Digital Reference, and cases with high blast count generally showed worse cytogenetic findings. Our results demonstrate the need for better counting methods if significant decisions are made based on microscopic enumeration of blasts. Further efforts should be made to develop markers to better define blast cells and perhaps incorporate automated digital imaging technologies to enumerate them. Also, consideration should be given to quantifying blasts per marrow area in biopsies instead of per nucleated cells.

KW - Acute leukemia

KW - Blast count

KW - Bone marrow

KW - Myelodysplastic syndrome

UR - https://www.scopus.com/pages/publications/85051533513

U2 - 10.1053/j.seminhematol.2018.07.001

DO - 10.1053/j.seminhematol.2018.07.001

M3 - Article

C2 - 30573046

SN - 0037-1963

VL - 56

SP - 58

EP - 64

JO - Seminars in Hematology

JF - Seminars in Hematology

IS - 1

ER -