Prognostic Significance of Beta-2 Microglobulin (B2M) in Adult Acute Lymphoblastic Leukemia (ALL).

Abstract 4679

Beta-2 microglobulin (B2M) is 12-kDa light chain protein that binds to the alpha chain of class 1 MHC molecules, dissociated into extracellular fluids after degradation of HLA. Elevated levels of serum B2M have historically been associated with a poor prognosis in several lymphoproliferative disorders. The prognostic relevance of B2M in myeloid disorders such as acute myelogenous leukemia and myelodysplastic syndrome has also been noted, in some cases providing further refinement of existing prognostic models. The significance of pretreatment serum B2M levels has not been extensively studied in adult ALL. In our historical experience with the conventional VAD (vincristine, doxorubicin, dexamethasone) regimen, elevated levels of B2M were associated with a lower complete remission (CR) rate, worse survival (OS), and higher propensity for development of CNS leukemia, after adjusting for renal dysfunction and older age [Kantarjian, Am J Med 93:599, 1992]. The analysis was somewhat limited by the strong negative impact of the mature B-cell ALL subset were the significantly high levels of B2M were associated with poor prognosis in the era prior to intensive multi-agent chemotherapy regimens. We assessed the associations of pretreatment B2M levels with outcome in 320 adolescents and adults with de novo ALL (Burkitt leukemia/lymphoma, Philadelphia chromosome positive ALL, and lymphoblastic lymphoma subtypes were excluded from the analysis) treated with the more intensive hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) and its variants (modified hyper-CVAD with or without anthracycline intensification and with or without rituximab). Median serum B2M level was 3 mg/L (range 0-14.7). As observed previously, the CR rate was lower for patients (pts) with elevated levels of B2M, an effect which persisted after excluding the elderly subset and accounting for renal dysfunction (93% versus 98%, p=.02). The 3-yr rates for CRD and OS were also worse if B2M was elevated above the median, 55% vs 70% (p=0.09) and 60% vs 70% (p=.01), respectively. These findings confirm the prior observations in a larger more homogenous population of de novo ALL treated with intensive chemotherapy. A limited multivariate analysis identified the independent prognostic influence of B2M on survival. Additional analyses will be conducted to determine how these observations can be best incorporated into clinical practice.