Acute Erythroleukemia Morphology Does Not Confer an Unfavourable Prognosis in Itself. Results of a Subgroup Analysis of the Prospective Randomized AML96-, AML2003 and AML60+ Studies of the Study Alliance Leukemia (SAL)

Acute erythroleukemia (AEL) represents a rare type of acute myeloid leukemia accounting for less than 5% of all cases. So far, according to WHO classification this AML entity is thought to have a poor prognosis in itself.

3267 patients with newly diagnosed AML were treated according to the protocols of the AML96, AML2003 or AML60+ studies of the Study Alliance Leukemia (SAL). 116 of these patients had acute erythroleukemia (AEL). The median age both for patients with AEL and non-AEL was 57 years.

We assessed the influence of relevant clinical and demographic parameters, FLT3-ITD, NPM1 status and cytogenetics on complete remission rates (CR), overall survival (OS) and event free survival (EFS) separately in AEL and non-AEL patients.

Compared to non-AEL AML, significantly more AEL were due to secondary causes than non-AEL AML (31% versus 20.4%; p=0.024). NPM1 mutations were found in 11.1% (out of 99) of the patients with AEL and in 32.8% (out of 2693) of the patients with non-AEL AML (p<0.001). Surprisingly, both the FLT3-ITD mutation and high FLT3-ITD ratios > 0.8 were found less frequently in AEL (FLT3-ITD mutation in 4.9% vs 23.3%; p=0.001; FLT3-ITD ratio >0.8 in 0% vs. 33.4%; p<0.001).

The cytogenetic aberrations +8, −7 and complex aberrant karyotype (>/= 3 independent aberrations) were found more often in the AEL cohort (14.8%, 10.3% and 26.7%) than in the non-AEL AML cohort (8.9%, 5% and 13.2%) (p=0.036, p= 0.01 and p <0.001, respectively).

Despite these differences, no significant differences in CR rates, OS and EFS were found between both groups. This finding was confirmed in a multivariate analysis including cytogenetics, molecular markers and clinical parameters (LDH, WBC, blast count, platelet count and ECOG). According to the analysis, ALE morphology was not an independent prognostic factor for OS and EFS.

With the AEL group, patients with monosomy 7 (n=12) had a higher median blast count (NEC) of 62% and shorter median OS with 5.7 months compared to patients with AEL and no monosomy 7 (n=104) with a median blast count (NEC) of 43% (p=0.013) and an median OS with 15.7 months (p=0.016).

A complex aberrant karyotype was found more often in patients with secondary AEL than in patients with de novo AEL (p=0.037). Significant differences were also seen in patients with AEL and complex aberrant karyotype compared to AEL without complex aberrant karyotype with respect to CR rates (54.8% versus 77.6%; p=0.016), OS (6.2 versus 17.4 months; p<0.000) and EFS (2.9 versus 6.2 months; p=0.007).

In patients with AEL and abn17p/-17 (n=15), lower median platelet counts (31 versus 48 ×10⁶/μl; p=0.017), a worse OS (6.4 vs 15.7 months; p=0.011) and EFS were observed (1.7 vs 5.7 months; p=0.046).

According to our data, the characteristic morphological features of acute erythroleukemia do not confer an unfavorable prognosis in itself. Furthermore, we can confirm the relevant influence of established prognostic factors such as cytogenetics and disease status within the AEL subgroup.

Off Label Use: sorafenib for the treatment of acute myeloid leukemia.