lmo Laboratory Medicine Online Lab Med Online ∗∗ 2093-6338 The Korean Society for Laboratory Medicine 10.3343/lmo.2019.9.3.126 lmo-9-126 Original Article Large Unstained Cell, Blast Suspect and Delta Neutrophil Index ll Analyzed with Automated Hematology Analyzer as Parameters for the Prediction of Acute Leukemia Relapse HwangNaraeM.D. KimYu KyungM.D. SuhJang SooM.D. Department of Clinical Pathology, School of Medicine, Kyungpook National University, Daegu, Korea Corresponding author: Jang Soo Suh, M.D., Ph.D. https://orcid.org/0000-0002-9684-2020 Department of Clinical Pathology, School of Medicine, Kyungpook National University, 680 Gukchebosang-ro, Jung-gu, Daegu 41944, Korea Tel: +82-53-200-5293, Fax: +82-53-200-3367, E-mail: suhjs@knu.ac.kr 07 2019 20 07 2019 9 3 126 132 29062018 10112018 25112018 Copyright © 2019 The Korean Society for Laboratory Medicine 2019 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background

Here we investigated the clinical utilities of blast suspect, large unstained cell (LUC), delta neutrophil index ll (DN ll), and delta neutrophil index l (DN l), analyzed in peripheral blood samples with automated hematology analyzers to predict the relapse of acute leukemia.

 Methods

We retrospectively reviewed the medical records of 112 patients, including 56 patients with acute leukemia relapse and 56 controls. Blast suspect, LUC, DN ll, and DN l were compared between the control and leukemia relapse groups.

 Results

Significant differences in blast suspect (P<0.001), LUC (P<0.001), DN ll (P<0.001), and DN l (P=0.002) were observed between the leukemia relapse and control groups. The areas under the curve (AUC) value was 0.927 for blast suspect (95% confidence interval [ CI]: 0.8750.978, P<0.001), 0.868 for LUC (95% CI: 0.794–0.941, P<0.001), and 0.900 for DN ll (95% CI: 0.841–0.960, P<0.001). Logistic regression analysis for the prediction of leukemia relapse revealed odds ratio values of 1.52 (95% CI: 1.26–1.96, P=0.0002) for blast suspect, 1.66 (95% CI: 1.27–2.42, P=0.0019) for LUC, 1.16 (95% CI: 1.08–1.29, P=0.0014) for DN ll, and 1.05 (95% CI: 1.01–1.13, P=0.0845) for DN l.

 Conclusions

Multiple parameters provided by automated blood cell analyzers may serve as powerful ancillary tools for the prediction and diagnosis of leukemia relapse.

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Box plot of blast suspect (A), LUC (B), DN II (C), DN I (D) in control and leukemia relapse groups.

Kaplan–Meier overall survival analysis of patients with leukemia relapse with blast suspect (A), LUC (B), DN II (C) and DN I (D). Dotted line represents patients with leukemia relapse in the third quartile (blast suspect >15.43%, LUC >11.65%, DN II >25.7%, DN I >4.25%) and solid line represents patients with leukemia relapse in the first to third quartile.

Clinical Characteristics of 112 patients

  Control (N=56) Relapse (N=56) P
Age (yr) 49.7±15.6 53.1±14.0 0.226
Sex
F (%) 23 (41.1) 25 (44.6)  
M (%) 33 (58.9) 31 (55.4)  
BM blast (%) [IQR] 1.0 [0.6–1.4] 61.7 [44.0–85.8] <0.001
PB blast (%) [IQR] 0.0 [0.0–0.0] 22.0 [6.5–60.0] <0.001
Hb (g/dL) 12.3±2.2 10.5±2.1 <0.001
WBC (×109/L) [IQR] 5.8 [4.6–7.4] 6.3 [2.4–17.0] 0.509
ANC (×109/L) [IQR] 3.3 [2.3–4.6] 1.8 [0.6–4.6] 0.017
PLT (×109/L) [IQR] 183.0 [146.0–232.0 0] 45.0 [25.0–83.0] <0.001
Subtype (%)
N 27 (48.2) 0 (0.0)  
ALL 12 (21.4) 14 (25.0)  
ALL L1 3 (5.4) 1 (1.8)  
ALL L2 7 (12.5) 13 (23.2)  
ALL L3 2 (3.6) 0 (0.0)  
AML 14 (25.0) 40 (71.4)  
AML M0 0 (0.0) 2 (3.6)  
AML M1 1 (1.8) 0 (0.0)  
AML M2 3 (5.4) 18 (32.2)  
AML M3 1 (1.8) 2 (3.6)  
AML M4 6 (10.7) 4 (7.1)  
AML M4Eo 1 (1.8) 4 (7.1)  
AML M5a 0 (0.0) 2 (3.6)  
AML M5b 2 (3.6) 6 (10.7)  
AML M6 0 (0.0) 1 (1.8)  
AML M7 0 (0.0) 1 (1.8)  
MPAL 2 (3.6) 2 (3.6)  
T 1 (1.8) 0 (0.0)  

Data are presented as mean±standard deviation or median [IQR]. Abbreviations: IQR, interquartile range; F, female; M, male; BM, bone marrow; PB peripheral blood; DN I, delta neutrophil index I; DN II, delta neutrophil index ll; LUC, large unstained cell; WBC, white blood cell; PLT, platelet; N, normal; T, T lymphoblastic leukemia; MPAL, mixed phenotype acute leukemia; Hb, hemoglobin.

AUC of blast suspect, LUC, DN II, and DN I

Parameter AUC (95% CI) Cutoff (%) Sensitivity (%) Specificity (%) P
Blast suspect 0.927 (0.875–0.978) 5.5 82.1 96.4 <0.001
LUC 0.868 (0.794–0.941) 3.9 83.9 89.3 <0.001
DN II 0.900 (0.841–0.960) 6.8 83.9 85.7 <0.001
DN I 0.670 (0.570–0.771) 2.2 57.1 76.8 0.639

Abbreviations: DN I, delta neutrophil index I; DN II, delta neutrophil index ll; LUC, large unstained cell; AUC, area under the curve; CI, confidence interval.

Results of univariate logistic regression analysis

Parameter OR 95% CI P
Blast suspect 1.52 1.26–1.96 0.0002
LUC 1.66 1.27–2.42 0.0019
DN II 1.16 1.08–1.29 0.0014
DN I 1.05 1.01–1.13 0.0845

Abbreviations: DN I, delta neutrophil index I; DN II, delta neutrophil index ll; LUC, large unstained cell; CI, confidence interval; OR, odds ratio.

Comparison of parameters between control and relapse groups with less than 5% blasts in the peripheral blood

Parameter Control (N=9) Relapse (N=9) P
BM blast (%) 1.0 (0.6–1.3) 47.9 (45.0–60.2) <0.001
PB blast (%) 0.0 (0.0–0.0) 1.0 (1.0–2.0) 0.002
Hb (g/dL) 11.5±2.6 10.7±1.5 0.440
WBC (×109/L) 5.5 (4.5–5.9) 2.1 (2.0–3.9) 0.038
ANC (×109/L) 3.6 (3.2–4.5) 1.3 (0.7–2.4) 0.050
PLT (×109/L) 172.6±53.5 68.4±71.0 0.003
Blast suspect (%) 0.5 (0.4–1.1) 2.0 (1.5–5.8) 0.019
LUC (%) 1.9 (0.9–3.5) 4.8 (2.6–5.6) 0.085
DN II (%) 0.9 (0.5–2.6) 11.1 (5.9–13.3) 0.024
DN I (%) −0.9 (−1.6–0.3) 4.5 (−1.1–6.3) 0.102

Abbreviations: BM, bone marrow; PB, peripheral blood; WBC, white blood cell; ANC, absolute neutrophil count; PLT, platelet; LUC, large unstained cell; DN II, delta neutrophil index ll; DN I, delta neutrophil index I; Hb, hemoglobin.