Tao Zhou, Zengfeng Ni, Wenjing Fan, Jing Xu, Jing Qin, Kaiyue Wang, Rui Wang, Yaping Li
A baseline platelet count <50 × 109/L was not independently associated with induction severe bleeding after excluding patients with bleeding at diagnosis but was associated with lower 24-month OS in this retrospective AML cohort. The bleeding finding was sensitive to endpoint definition and should be interpreted cautiously. This study did not assess incremental predictive value beyond established AML risk systems; the findings should therefore be considered hypothesis-generating and require prospective external validation.
OBJECTIVE: To investigate the association between baseline platelet count at diagnosis and complete remission (CR) rate, severe bleeding during induction, and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML).
METHODS: This multi-center retrospective cohort study enrolled 356 non-acute promyelocytic leukemia (non-APL) AML patients treated with first-line therapy between January 2020 and December 2025. Patients were classified as having a low baseline platelet count (<50 × 109/L, n=218) or a normal/high count (≥50 × 109/L, n=138). The primary outcomes were severe bleeding (CTCAE grade ≥3) occurring during induction and OS administratively censored at 24 months. The primary severe-bleeding analysis excluded patients with bleeding already present at diagnosis (n=125) to avoid endpoint-covariate overlap; the full-cohort analysis served as a sensitivity check. Parsimonious Firth logistic and Cox models, Kaplan-Meier analysis, 1:1 propensity score matching (PSM), continuous platelet modeling, restricted cubic splines (RCS), common-outcome censoring scenario analyses, an intensive-induction subgroup analysis, and center- and calendar-period sensitivity analyses were used.
RESULTS: CR (53.7% vs. 50.7%, P=0.665) and CR/CRi rates (63.3% vs. 68.8%, P=0.339) did not differ significantly between groups. After excluding patients with bleeding at diagnosis, low baseline platelet count was not independently associated with severe bleeding in the primary Firth logistic analysis (OR=1.761, 95% CI 0.631-5.583, P=0.287; 20 events in 231 patients), although the association remained in the full-cohort sensitivity analysis (adjusted OR=2.753, 95% CI 1.318-5.749, P=0.007). Kaplan-Meier analysis showed lower 24-month OS in the low-platelet group (58.2% vs. 77.8%; log-rank P<0.001), and the adjusted 24-month Cox model yielded an HR of 1.811 (95% CI 1.145-2.864, P=0.011). The association persisted after additional adjustment for participating center (HR=1.896, 95% CI 1.192-3.017, P=0.007). Per 10 × 109/L higher baseline platelet count, the adjusted 24-month death hazard was 11.3% lower. The OS association was also directionally consistent in the intensive-induction subgroup (HR=2.402, P=0.007). Both common-outcome scenarios produced hazard ratios in the same direction as the primary analysis; however, these scenarios do not address differential informative censoring between platelet groups. Restricted cubic spline analyses showed a significant, approximately linear association between platelet count and 24-month OS and no significant overall association with severe bleeding in the primary analysis. In the PSM sensitivity analysis, which retained residual covariate imbalance, the 24-month OS estimate remained significant (HR=1.981, 95% CI 1.228-3.193, P=0.005). The matched severe-bleeding analysis was not informative because of insufficient events after excluding patients with bleeding at diagnosis. Per 10 × 109/L higher baseline platelet count, the adjusted odds of severe bleeding decreased by 16.8% (OR=0.832, 95% CI 0.701-0.988, P=0.036), but this continuous association was not confirmed by categorical or spline analyses.
CONCLUSION: A baseline platelet count <50 × 109/L was not independently associated with induction severe bleeding after excluding patients with bleeding at diagnosis but was associated with lower 24-month OS in this retrospective AML cohort. The bleeding finding was sensitive to endpoint definition and should be interpreted cautiously. This study did not assess incremental predictive value beyond established AML risk systems; the findings should therefore be considered hypothesis-generating and require prospective external validation.