Prognostic Significance of β-2 Microglobulin Levels in Acute Myeloid Leukemia: Analysis of 1293 Patients.

Introduction: β-2 Microglobulin (β₂M) is a single polypeptide chain that is linked non-covalently to the major histocompatibility complex class I cell surface antigen. Its specific function is unknown, but serum β₂M levels reflect membrane turnover (tumor mass and growth rate) and renal function. Elevated serum β₂M levels are associated with poor survival in several hematologic malignancies, but its prognostic significance in acute myeloid leukemia (AML) is unknown. The purpose of this study was to determine the association between β₂M levels and pretreatment characteristics and clinical outcomes in newly diagnosed AML.

Patients and Methods: From 1990 to 2005, β₂M levels were prospectively measured in 1293 patients with AML. Serum β₂M was quantified by radioimmunoassay (normal range, 0.7–2.0 mg/L).

Results: The median patient age was 61 yrs (range, 16–89 yrs); 54% were >60 yrs. Cytogenetics were favorable in 7% of patients, intermediate in 60%, poor-risk in 29%, and 4% of patients had insufficient metaphases. Zubrod performance status (PS) was 0–1 in 73% of patients, 2 in 20%, and 3–4 in 7%. Eighty-five percent had de novo AML, and 91% received Ara-C-based therapy. High β₂M levels were more common in patients who were older (cor=0.22); had high early risk of mortality (ERM) score (cor =0.33); high levels of creatinine (cor=0.63), and uric acid (cor=0.29), high white blood cell counts (cor=0.26), or circulating monocytes (cor = 0.23); prolonged prothrombin time (PT) (cor=0.26); worse PS (cor=0.27); and low albumin levels (cor=−0.22)(p<0.001 for all variables). High β₂M levels were correlated with worse-risk cytogenetics (p=0.03), RAS mutation (p=0.003), baseline infection (p=0.04), and secondary AML (p=0.01). The median follow-up of surviving patients was 3.8 yrs.

In multivariate analysis, independent factors predicting response were younger age (p<0.0001), better-risk cytogenetics (p<0.0001), Ara-C-based therapy (p<0.0001), lower levels of β₂M (p=0.0001), shorter PT (p=0.006), de novo AML (p=0.007), lower LDH levels (p=0.02), and lower bilirubin levels (p=0.03). Factors independently prognostic of longer survival were younger age (p<0.0001), better-risk cytogenetics (p<0.0001), better PS (p<0.0001), de novo AML (p<0.0001), lower serum uric acid levels (p=0.0001), lower LDH levels (p=0.0007), shorter PT (p=0.0009), lower β₂M levels (p=0.003), higher hemoglobin levels (p=0.005), Ara-C-based therapy (p=0.007), and lower bilirubin levels (p=0.02). Factors independently prognostic of longer event-free survival (EFS) were younger age (p<0.0001), better-risk cytogenetics (p<0.0001), Ara-C-based therapy (p<0.0001), de novo AML (p=0.0001), better PS (p=0.0003), lower uric acid levels (p=0.0004), lower LDH levels (p=0.001), lower β₂M levels (p=0.002), higher hemoglobin levels (p=0.003), shorter PT (p=0.02), and lower bilirubin levels (p=0.045).

Conclusions: Elevated serum β₂M levels are an independent adverse prognostic factor for response, survival, and EFS in the context of established prognostic factors for AML.