Prognostic Value of Immunophenotype in Patients with Non-Promyelocytic Acute Myeloid Leukemia Treated with Intensive Chemotherapy. A Single Centre Study.

Abstract

Background: The prognostic significance of the expression pattern of certain cell surface markers in acute myeloid leukemia (AML) is controversial.Objectives: Analyze the impact of the expression of certain cell surface markers on complete remission rate (CR) and relapse free survival (RFS), in a large series of adult patients with non-promyelocytic AML treated with intensive chemotherapy.Methods: From 1989 to 2007, 451 adult patients (median age 57 years, range 15–80 years) diagnosed with non-promyelocytic AML, received first induction chemotherapy in our institution. Induction therapy consisted of the combination of cytarabine and anthracycline with or without a third agent in 95% of patients and other regimens in the remaining 5%. The post-remission treatment consisted of consolidation chemotherapy followed or not by stem cell transplantation. The inmunophenotypic analysis of bone marrow samples at diagnosis was evaluable in 395 patients (88%). Positivity was defined as more than 20% blasts expressing a specific antigen. It was possible to evaluate the percentage of positive blasts for the following antigens: CD33 (395 patients), CD13 (391), HLA-DR (382), CD14 (375), CD34 (364), CD7 (354), CD11b (350), CD4 (347), CD36 (343), CD15 (326), CD9 (321), CD2 (315), CD38 (250), CD71 (233), myeloperoxidase (MPX) (186), CD117 (178) and CD56 (173). We conducted a univariate and mutivariate analysis in order to define the impact of the expression of cell surface markers on CR rate and RFS.Results: Overall, 256 patients (58.3%) achieved a CR. The following characteristics were associated with a lower probability of CR: age >60 years, performance status by means of ECOG scale ≥2, peroxidase staining in <75% of blasts, and high-risk karyotype (in all, p<0.001). The positivity of CD34 and the negativity of CD15 and MPX, were associated with a lower CR rate (p=0.005, p=0.04 and p<0.001, respectively), due to a higher rate of resistance (p<0.001, p=0.004 and p<0.001, respectively). Multivariate analysis showed that WBC >50×109/l, high-risk karyotype, CD34 positivity and MPX negativity were independent unfavourable factors for CR. The median follow-up of the cohort was 81 months and the overall RFS at 5 years was 35%. The following factors are associated with a lower RFS: CR achievement with 2 cycles (15% vs 37%, p<0.001), age >60 years (16% vs 44%, p<0.001), peroxidase staining in <75% of blasts (26% vs 49%, p=0.001), high-risk karyotype (0% vs 39%, p=0.03), CD2 positivity (11% vs 40%, p=0.008) and MPX negativity (16% vs 40%, p=0.02). Multivariate analysis showed that age >60 years, CR achievement with 2 cycles and MPX negativity were independent unfavourable factors for RFS.Conclusion: The AML with an immature immunophenotype, like those with CD34 positivity or MPX negativity, shows a higher resistance to induction chemotherapy. We also have observed a shorter remission duration in those AML with CD2 positivity or MPX negativity.