CD71 as an independent prognostic factor in pediatric B-ALL: a regional multicenter retrospective study in Southern China (SCCLG-ALL-2016)

Background: Despite high cure rates in pediatric B-cell acute lymphoblastic leukemia (B-ALL), relapse remains a major challenge. Current risk stratification systems fail to identify a subset of occult high-risk (HR) patients. Transferrin receptor 1 (CD71), a key regulator of iron uptake, is often overexpressed in aggressive tumors; however, its independent prognostic value in pediatric B-ALL has not been fully elucidated. Objectives: To evaluate the independent prognostic significance of CD71 expression in a large cohort of pediatric B-ALL patients and to determine its utility in identifying HR subgroups. Design: A retrospective, multicenter cohort study. Methods: We analyzed 1207 pediatric B-ALL patients treated under the South China Children’s Leukemia Group-ALL-2016 protocol between January 2016 and June 2023 across 20 centers in Southern China. CD71 expression was assessed by flow cytometry at diagnosis, with positivity defined as ⩾20% expression on blast cells. We analyzed associations between CD71 status, clinical characteristics, and survival outcomes using Kaplan–Meier methods and multivariate Cox regression models. Results: CD71 positivity was rare in B-ALL (1.0%) compared to T-ALL (15.6%). Clinically, CD71-positive B-ALL patients presented with significantly lower initial white blood cell (WBC) counts (median 4.0 vs 10.0 × 10 9 /L, p = 0.015). Despite this lower peripheral tumor burden, CD71 positivity was associated with extremely poor outcomes. The 5-year cumulative incidence of relapse (CIR) was significantly higher in the CD71-positive group compared to the negative group (39.4% vs 10.1%, p = 0.004). Multivariate analysis confirmed that CD71 positivity is an independent risk factor for relapse (hazard ratio (HR) = 5.94, p = 0.003) and adverse events (HR = 4.868, 95% confidence interval: 1.512–15.671, p = 0.008), irrespective of age, WBC, genetic subtype, or minimal residual disease status. Conclusion: CD71 expression identifies a rare but biologically distinct B-ALL subgroup characterized by aggressive behavior despite low initial WBC counts. These findings indicate that the inclusion of CD71 in diagnostic panels may help to optimize current risk stratification systems, serving as a critical tool to recognize occult HR patients who might otherwise be under-stratified by conventional prognostic markers. Clinical trial registration: The trial is registered with the Chinese Clinical Trial Registry (Chi-CTR; https://www.chictr.org.cn/ ; number ChiCTR2000030357; Registration date: February 29, 2020).