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This study of 1,826 pediatric acute lymphoblastic leukemia patients found that hyperleukocytosis (white blood cell count above 100,000/µL) at diagnosis strongly predicts worse outcomes in B-cell ALL patients, even after accounting for other risk factors. Children with B-ALL and hyperleukocytosis had significantly lower 5-year event-free survival (65% vs 89%) and overall survival (78% vs 93%) compared to those without hyperleukocytosis, and were more than twice as likely to have detectable disease after initial treatment. The effect was dose-dependent, with higher white blood cell counts associated with progressively worse outcomes across all risk categories.
Why it matters
Despite modern risk-adapted treatment protocols that intensify therapy for high-risk patients, hyperleukocytosis continues to identify an aggressive subtype of pediatric B-ALL with persistently poor outcomes. This suggests that current treatment intensification strategies may be insufficient for these patients, who may require novel therapeutic approaches or alternative treatment strategies to improve survival rates.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Hyperleukocytosis (white blood cell [WBC] count >100 000/uL) at diagnosis is an important prognostic risk factor in pediatric acute lymphoblastic leukemia (ALL), though its significance with contemporary therapy is unclear. We analyzed 1 826 pediatric ALL patients from a multi-institution cohort to determine whether hyperleukocytosis independently predicts outcomes using multivariable Cox proportional hazard modeling. Hyperleukocytosis occurred in 211 patients (12%), with 121 having B-ALL, and showed no prognostic significance in T-ALL patients. In B-ALL, 5-year event-free survival (EFS) was 65% versus 89% for non-hyperleukocytosis patients, and overall survival (OS) was 78% versus 93%. After adjustment for age, cytogenetic risk, central nervous system disease status, and treatment site, hyperleukocytosis remained an independent predictor of end-of-induction minimal residual disease (MRD) positivity (odds ratio 2.53 [95% confidence interval [CI]: 1.71-3.94; p<0.001]), inferior EFS (hazard ratio [HR] 2.44; 95% CI: 1.77-3.38; p<0.001) and inferior OS (HR 2.00; 95% CI: 1.29-3.12; p=0.002). A continuous dose-response relationship was observed between WBC count and these outcomes. Survival associations persisted across all cytogenetic risk categories and MRD strata. Despite risk-adapted therapy with treatment intensification for high-risk features, hyperleukocytosis identifies an aggressive B-ALL phenotype with persistently inferior outcomes, suggesting these patients may benefit from novel therapeutic approaches.