Clinicopathological Features and Exploratory Outcome Associations of Bone Marrow Fibrosis in Newly Diagnosed Acute Lymphoblastic Leukemia: A Single-Center Retrospective Cohort Study.

Abstract

Bone marrow fibrosis (MF) reflects stromal remodeling and has been associated with treatment resistance and adverse outcomes in hematologic malignancies; however, its clinical significance in acute lymphoblastic leukemia (ALL) remains uncertain. We retrospectively analyzed 103 patients with newly diagnosed ALL and documented MF grades between 2018 and 2023, comparing patients with MF grades 0-1 and those with MF grades 2-3. Higher-grade MF was present in 50 patients (48.5%). B-ALL accounted for a greater proportion of cases in the MF 2-3 group than in the MF 0-1 group (94.0% vs. 69.8%; nominal p = 0.002), and this difference remained statistically significant after false discovery rate correction. No mutation-level difference between the MF groups remained significant after correction for multiple comparisons. In Cox regression, MF 2-3 was associated with a lower observed hazard of death compared with MF 0-1 (adjusted HR, 0.26; 95% CI, 0.12-0.55; p < 0.001). A similar association was observed in a sensitivity analysis restricted to patients with B-ALL (adjusted HR, 0.30; 95% CI, 0.13-0.70; p = 0.005). Given the retrospective design, limited number of deaths, and potential residual confounding, this unexpected inverse association should be considered exploratory and should not be interpreted as evidence of a biologically protective effect of MF. In conclusion, higher-grade MF was common in newly diagnosed ALL and was associated with B-lineage disease. An unexpected inverse association between MF grade and observed mortality was identified in this cohort and persisted in the B-ALL-restricted sensitivity analysis. External validation is required before MF can be considered for prognostic stratification or treatment decision-making.