Abstract

Translocation (8;21)(q22;q22) and inversion of chromosome 16 [inv(16) (p13q22)] are considered good-risk cytogenetic abnormalities in acute myeloid leukemia (AML) accounting for 15% of primary AML cases (Blood. 2002 Dec 15;100(13):4325–36) and are characterized at the molecular level by disruption of genes encoding subunits of core binding factor (CBF). Increasing age, increasing peripheral blast percentage and complex cytogenetics are associated with poor overall survival in these patients (Br J Haematol. 2006 Oct;135(2):165–73). Here we assess differences in patient characteristics and outcomes between the primary and secondary core binding factor AML. One hundred eighty nine CBF AML patients treated at our institution were studied; 18 (9.5%) had secondary AML. Patients with secondary CBF AML were older (p= 0.02, median ages 57 vs. 44 years) and had lower WBC counts (p=0.03) (Table1). Overall survival (OS) was worse in the secondary AML patients (94 weeks versus 621 weeks, p=0.0016) (Figure 1). Age, hemoglobin, platelet count, and bilirubin were significantly associated with OS in the univariate analysis. In the multivariate analysis, after adjusting for age, hemoglobin, WBC, and bilirubin, secondary CBF AML was marginally significantly associated with worse OS (hazard ratio 1.884, CI95% 0.979–3.625, p=0.058) but not worse PFS (p= 0.15) (Table 2). These data suggest that the secondary CBF AML has much poorer prognosis than the primary CBF AML, further indicating that “CBF AML” is not a homogeneous entity with a uniformly good prognosis.

Table 1:

Summary statistics of patients’ continuous characteristics by abnormality status

Patient characteristicsTotal patientsPrimary AML (n=171, male=96)Secondary AML (n=18, male=8)p-value (primary vs secondary AML)
Median (range)Median (range)Median (range)
Age (years) 44 (16–88) 44 (16–88) 57 (31–75) 0.02 
WBC (103/mm314.7 (0.6–387) 16.4 (0.6–387) 6.6 (0.8–103.8) 0.03 
Hemoglobin (g/dl) 8.1 (2.5–14.3) 8.2 (2.5–14.3) 7.8 (4.8–10.8) 0.33 
Platelet count (103/mm338 (5–350) 38 (5–350) 39 (9–139) 0.88 
Bilirubin (mg/dl) 0.6 (0.0–15.3) 0.6 (0.0–5.0) 0.6 (0.1–15.3) 0.94 
Creatinine (mg/dl) 0.9 (0.5–2.9) 0.9 (0.5–2.9) 0.9 (0.5–1.8) 0.66 
Patient characteristicsTotal patientsPrimary AML (n=171, male=96)Secondary AML (n=18, male=8)p-value (primary vs secondary AML)
Median (range)Median (range)Median (range)
Age (years) 44 (16–88) 44 (16–88) 57 (31–75) 0.02 
WBC (103/mm314.7 (0.6–387) 16.4 (0.6–387) 6.6 (0.8–103.8) 0.03 
Hemoglobin (g/dl) 8.1 (2.5–14.3) 8.2 (2.5–14.3) 7.8 (4.8–10.8) 0.33 
Platelet count (103/mm338 (5–350) 38 (5–350) 39 (9–139) 0.88 
Bilirubin (mg/dl) 0.6 (0.0–15.3) 0.6 (0.0–5.0) 0.6 (0.1–15.3) 0.94 
Creatinine (mg/dl) 0.9 (0.5–2.9) 0.9 (0.5–2.9) 0.9 (0.5–1.8) 0.66 
Table 2:

Multivariate Cox proportional hazards model in estimating the association between covariates and patients’ survival

VariableHazard ratio (95% CI)p-value
Abnormality (secondary vs primary) 1.884 (0.979–3.625) 0.058 
Age (1 year increase) 1.028 (1.012–1.044) 0.0004 
Hemoglobin (1gm/dl increase) 0.864 (0.769–0.970) 0.014 
WBC (103/mm3 increase) 1.003 (1.000–1.007) 0.061 
Bilirubin (1 mg/dl increase) 1.179 (1.044–1.332) 0.008 
VariableHazard ratio (95% CI)p-value
Abnormality (secondary vs primary) 1.884 (0.979–3.625) 0.058 
Age (1 year increase) 1.028 (1.012–1.044) 0.0004 
Hemoglobin (1gm/dl increase) 0.864 (0.769–0.970) 0.014 
WBC (103/mm3 increase) 1.003 (1.000–1.007) 0.061 
Bilirubin (1 mg/dl increase) 1.179 (1.044–1.332) 0.008 

Author notes

Disclosure: No relevant conflicts of interest to declare.