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Background <p>Leukoerythroblastosis (LEB), defined as the concurrent detection of immature granulocytes (IG) and nucleated red blood cells (NRBC) in peripheral blood, may reflect profound bone marrow stress in sepsis. Although IG or NRBC positivity has been associated with poor outcomes, it remains uncertain whether LEB itself confers an increased risk of mortality in patients with sepsis and how its prognostic significance compares with other smear-based patterns, including isolated IG or NRBC positivity and Double-negative findings.</p> Methods <p>This single-center retrospective cohort study comprised adult intensive care unit (ICU) patients with sepsis between April 2011 and March 2023. If the automated hematology analyzer generated an abnormal flag, smear microscopy was performed, and the patients were classified accordingly. The LEB group was defined as concurrent IG and NRBC on the same smear; the single-positive group included IG-only, NRBC-only, and non-concurrent both-positive findings; and the Double-negative group was defined as undetectable IG and NRBC on smear review or no smear review due to the absence of analyzer flags. To minimize immortal-time bias, we performed a day-7 landmark analysis including only patients who survived for at least 7 days after ICU admission. Associations with 90-day mortality were evaluated using Cox proportional hazards models adjusted for prespecified covariates.</p> Results <p>Among 569 eligible patients, 110 (19.3%) were classified into the LEB group, 163 (28.6%) into the single-positive group, and 296 (52.0%) into the Double-negative group. The 90-day survival differed significantly among groups (log-rank <i>p</i> &lt; 0.001), driven by worse survival in the LEB group. In the multivariable Cox model (complete-case analysis; <i>n</i> = 553; 112 events), the LEB group had higher 90-day hazard of death than the Double-negative group (adjusted hazard ratio 1.917; 95% confidence interval 1.178–3.120; <i>P</i> = 0.009), whereas the single-positive group did not differ significantly (adjusted hazard ratio 1.025; 95% confidence interval 0.629–1.672; <i>P</i> = 0.921).</p> Conclusions <p>Among ICU patients with sepsis who survived for 7 days after ICU admission, LEB identified within 7 days after ICU admission was independently associated with increased 90-day mortality. Thus, LEB may reflect severe systemic stress and sepsis-associated hematopoietic dysfunction.</p>

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Leukoerythroblastosis was associated with 90-day mortality in adult ICU patients with sepsis: a retrospective cohort study

  • 期刊论文

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  • 发表日期：

    2026年7月18日

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  • Emi Fujii,
  • Tomoki Tanaka,
  • Naoto Mizumura,
  • Yuka Segoe,
  • Yugo Matsumoto,
  • Mitsuhiro Fujino,
  • Hidemitsu Miyatake,
  • Junji Shimizu,
  • Takuma Kishimoto,
  • Kazunori Fujino,
  • Yasuyuki Tsujita,
  • Hirotoshi Kitagawa,
  • Naoto Shiomi

摘要

Background

Leukoerythroblastosis (LEB), defined as the concurrent detection of immature granulocytes (IG) and nucleated red blood cells (NRBC) in peripheral blood, may reflect profound bone marrow stress in sepsis. Although IG or NRBC positivity has been associated with poor outcomes, it remains uncertain whether LEB itself confers an increased risk of mortality in patients with sepsis and how its prognostic significance compares with other smear-based patterns, including isolated IG or NRBC positivity and Double-negative findings.

Methods

This single-center retrospective cohort study comprised adult intensive care unit (ICU) patients with sepsis between April 2011 and March 2023. If the automated hematology analyzer generated an abnormal flag, smear microscopy was performed, and the patients were classified accordingly. The LEB group was defined as concurrent IG and NRBC on the same smear; the single-positive group included IG-only, NRBC-only, and non-concurrent both-positive findings; and the Double-negative group was defined as undetectable IG and NRBC on smear review or no smear review due to the absence of analyzer flags. To minimize immortal-time bias, we performed a day-7 landmark analysis including only patients who survived for at least 7 days after ICU admission. Associations with 90-day mortality were evaluated using Cox proportional hazards models adjusted for prespecified covariates.

Results

Among 569 eligible patients, 110 (19.3%) were classified into the LEB group, 163 (28.6%) into the single-positive group, and 296 (52.0%) into the Double-negative group. The 90-day survival differed significantly among groups (log-rank p < 0.001), driven by worse survival in the LEB group. In the multivariable Cox model (complete-case analysis; n = 553; 112 events), the LEB group had higher 90-day hazard of death than the Double-negative group (adjusted hazard ratio 1.917; 95% confidence interval 1.178–3.120; P = 0.009), whereas the single-positive group did not differ significantly (adjusted hazard ratio 1.025; 95% confidence interval 0.629–1.672; P = 0.921).

Conclusions

Among ICU patients with sepsis who survived for 7 days after ICU admission, LEB identified within 7 days after ICU admission was independently associated with increased 90-day mortality. Thus, LEB may reflect severe systemic stress and sepsis-associated hematopoietic dysfunction.