Between January 2006 to August 2010, a retrospective analysis was on 140 patients with newly diagnosed AML (age 15 years or older) treated at the division of hematology, the Yonsei university college of medicine. The diagnosis and classification of AML was determined according to the FAB classification.9 Patient with clinical de novo AML and secondary AML were eligible for this trial; however, patients with FAB AML types M0, M7 [always MPO-negative (MPO-)], or M3 [always 100% MPO-positive (MPO+)] were excluded.

The induction regimen for remission was comprised of idarubicin (12 mg/m²/day I.V. over 30 min on days 1-3) in combination with cytosine arabinoside (ara-C) (100 mg/m²/day I.V. continuous infusion on days 1-7). After achievement of a CR, the options for post-remission treatment were broad and choice of therapy was determined by the prognostic factors at diagnosis and beyond, patient and physician biases. Fifty-five (39%) patients were treated with 2-4 course of post-remission chemotherapy that included high-dose ara-C (3 g/m² I.V. every 12 hr on day 1, 3, and 5) as consolidation. Thirty-seven (26%) patients who had an available donor, went through alloHCT after several course of post-remission chemotherapy. Nine (16%) were assigned to autologous HCT (autoHCT).

Flow cytometric analysis of bone marrow and/or the peripheral blood cells was performed with an extensive panel of monoclonal antibodies according to (national) protocols currently in use in the different center. The reactivity with anti MPO, CD11c, CD13, CD14, CD15, CD33, CD65s and CD117, referred to as myeloid markers was analyzed. A case was considered to be positive for a marker if ≥20% of the blasts were positive according to EGIL guideline.10 In this analysis, we scored leukemias positive for anti-MPO if >50% of the blasts showed expression.

Chromosome analysis was performed on metaphases from preparations of bone marrow samples. The cytogenetic preparation and G-banding were carried out according to routine laboratory procedure.11 Chromosome was interpreted based on the International System for Human Cytogenetic Non-menclature. Patients were classified into a favorable, intermediate, or adverse risk group based on their karyotypes according to the MRC AML 10 study published.2 Diagnostic samples were also analyzed for mutations in the fms-related tyrosine kinase 3 gene (FLT3) [i.e., the internal tandom duplications (ITDs) and tyrosine kinase domain mutations at codons D835 and I836].

Patient characteristics in cases with or without MPO expression by risk factors were compared using the χ² test in case of discrete variables or using the t-test in case of continuous variables. OS was measures from diagnosis until death from any cause. Patients still alive at the date of last contact were censored at the last follow-up date. Disease-free survival (DFS) was measured from achieving CR until relapse, death from any cause or last follow-up. If patients who were not in remission at the time of transplantation, DFS were measured from the time of transplantation. OS and DFS were estimated using the Kaplan-Meier method, and were compared by the log-rank test according to the MPO expression. Furthermore, the simultaneous effect of risk factors on OS and DFS were analyzed using Cox's proportional-hazard model. Statistical significance is represented by two-tailed p values.

In approximately 60% of patients with AML, pre-treatment cytogenetic analysis reveals an abnormal karyotype. Intermediate cytogenetics were relatively common occurring in 62% of cases, and 28 patients were classified in the adverse risk group. MPO expression was associated with favorable cytogenetic risk group (p=0.015). Cytogenetically normal AML was identified in 80 patients (57%), FLT3-ITD was founded in 3 patients (7%) with MPO+ and 3 patients (11%) with MPO- group (p=0.676).

In this analysis, the median follow-up for the both groups was 12.2 months (range, 0.1-54.1). By the univariate analysis, the age was significant factors associated with OS and DFS (Table 4). The OS at 1 year were 48% in younger age (<60 years) while elderly (≥60 years) was dead within 1 year after diagnosis (p<0.001). The OS was not related with MPO expression (p=0.208) (Fig. 1A). The DFS at 1 year between two age group (<60 vs. ≥60 years) were 34% and 3%, respectively (p=0.019). Patients with MPO- group had an inferior DFS than in MPO+ group (1-year DFS; 26% vs. 50%, p=0.027) (Fig. 1B). In the multivariate analysis, all factors were not significant for OS, but the MPO was associated with better DFS (Table 5). Patients of MPO+ groups had a better DFS than MPO- groups [p=0.049; HR, 0.076; 95% confidence interval (CI), 0.06 to 0.997]. Fig. 2A presents OS and DFS in patients received transplant according to MPO expression. Within 46 patients performed transplant, the median DFS in 28 patients with MPO+ was not significantly different from in 18 MPO- patients (17.5 months vs. 6.8 months; p=0.289). The median OS in the MPO- group was relatively less than in the MPO+ group, but not statistically significant (28.6 months vs. 18.2 months; p=0.375). Also, in patients received an alloHCT (except autoHCT), DFS and OS in the MPO+ group were not statistically different from those in the MPO- group (Fig. 2B).