Risk Adapted Therapeutic Strategy of Acute Myeloid Leukemia
Authors: Mohty Razan , Massoud Radwan , Chakhachiro Zaher , Mahfouz Rami , Nassif Samer , Elcheikh Jean , Bazarbachi Ali 
Published: November 2019

In this "real-life" retrospective study, we assessed outcome after a "personalized" treatment strategy for patients with acute myeloid leukemia (AML) in a tertiary care center. Our strategy consisted of induction therapy adjusted to age, comorbidities and molecular abnormalities, as well as allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1), whenever possible, for patients with European Leukemia Net 2017 (ELN) intermediate or high-risk patients. Allo-SCT was followed by post-transplant maintenance consisting of 5-azacytidine (AZA) for most patients, or sorafenib for patients with FLT-3 ITD. We included 99 consecutive patients (65% male). The median age at diagnosis was 49 years (range, 18-88) with 28 patients older than 60. Karyotype was normal in 59 patients. Molecular analysis revealed core binding factor (CBF) mutation in 13 patients (13%), NPM1 mutation in 26 patients (26%), FLT3-ITD and FLT3-TKD mutation in 15 (15%) and 1 (1%) patient, respectively. According to the ELN 2017 classification, 24, 48 and 27 patients belonged to the low, intermediate and high-risk groups, respectively.
Patients aged <60 received mainly Idarubicin/Cytarabine induction regimen (sorafenib was added in 2 patients). Patients with CBF AML received Fludarabine/Cytarabine/ Idarubicine (FLAG-Ida) regimen (Gemtuzumab Ozogamicin GO was only added in 1 patient). The majority of the remaining older patients (age ³60) received AZA. Death during induction occurred in 7% of cases, being 6% for patients <60 and 11% for patients above 60. The overall CR rate was 76%, with 6 patients requiring a second induction to achieve CR1. In patients aged <60 and ³60 year-old, the CR1 rates were 82% and 61%, respectively. Allo-SCT was performed in CR1 in 26 patients belonging to the ELN 2017 intermediate and adverse risk groups, 5 of them were aged > 60. Of those 26 transplanted patients, 24 received post-allo-SCT maintenance consisting of AZA in 18 patients (69%) or sorafenib in 6 patients (23%). Allo-SCT was performed in 20 additional patients at time of relapsed and/or refractory disease, with 14 of them receiving post-transplant maintenance.
The median follow-up for alive patients was 35 months. For the whole cohort, the 3-year overall survival (OS) was 54%. In patients aged <60 and ³60, the 3-year OS was 63% and 31% respectively (p=0.002). The 3-year OS were 68%, 60% and 27% in ELN favorable, intermediate and adverse risk groups respectively (p=0.02). In patients who achieved CR after induction, the 3-year leukemia free survival (LFS) was 54% for the whole cohort (57% for patients <60 and 45% for patients ³60, p=0.71), with a 3-year LFS of 58%, 69% and 21% in ELN favorable, intermediate and adverse risk groups respectively (p=0.009). For 41 patients aged less than 60 with ELN intermediate or adverse risk group, the 3 year OS and LFS were 89% and 68% for the 21 patients who underwent allo-SCT in CR1 compared to 37% and 34% for 20 patients who were not transplanted in CR1 (p=0.003 and 0.011, respectively).
These results indicate an improved outcome for AML patients who receive a treatment strategy tailored to age, comorbidities, and disease risk with an overall 76% CR rate and a relatively low rate of mortality during induction (7%). The use of allo-SCT in CR1 followed by post-transplant maintenance significantly improved outcome of young patients (<60) with ELN intermediate or high-risk groups with a 3-year LFS for the ELN intermediate group (69%) likely exceeding that of the ELN favorable group (58%). Results of patients with the ELN favorable group could have been improved with a more systematic use of low dose GO for patients with CBF as well as a more frequent use of allo-SCT in CR1 for patients who remain MRD positive.

Disclosures
No relevant conflicts of interest to declare.