Prognostic impact of extramedullary disease in acute myeloid leukemia: A meta-analysis

Extramedullary disease (EMD) occurs in 1%-30% of acute myeloid leukemia (AML) patients and has been associated with adverse outcomes. However, the magnitude of its prognostic impact varies considerably across studies, possibly due to inconsistent terminology and diagnostic approaches. The definition of EMD in AML varies, typically employing three descriptors: EMD (comprehensive), extramedullary infiltration (EMI), and myeloid sarcoma/granulocytic sarcoma (MS/GS). This first comprehensive meta-analysis precisely quantifies EMD's prognostic impact, revealing a significant effect on overall survival (OS) (HR = 1.49, 95% CI, 1.34-1.67, p < .001) and event-free survival (EFS) (HR = 1.38, 95% CI, 1.03-1.84, p = .030). Importantly, our subgroup analyses demonstrate that prognostic impact varies significantly by EMD classification. The HR for EMI was 1.88 (95% CI, 1.52-2.31, p = .000); for EMD, it was 1.41 (95% CI, 1.20-1.66, p = .000); and for MS/GS, it stood at 1.18 (95% CI, 0.92-1.52, p = .188). Additionally, we analyzed the influence of EMD on the OS of AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and found that allo-HSCT may mitigate EMD's negative prognostic impact (HR = 1.19, 95% CI, 0.97-1.46, p = .092; Heterogeneity: I² = 0.0%, p = .860), confirming and quantifying this therapeutic benefit through meta-analysis for the first time. These findings highlight the need for standardized EMD definitions and suggest differential therapeutic approaches based on EMD subtype.