Independent Prognostic Impact of CD15 for Achievement of Complete Remission in Patients with Acute Myeloid Leukemia
Authors: Ceglie Teresa , Chisini Marta , Vozella Federico , Colafigli Gioia , Stefanizzi Caterina , Salaroli Adriano , D'Angiò Mariella , Mancini Marco , Diverio Daniela , Breccia Massimo , Mancini Francesca , Raponi Sara , Minotti Clara , Trisolini Silvia , Capria Saveria , Testi Anna Maria , Guarini Anna , Latagliata Roberto , De Propris Maria Stefania , Foa Robin 
Published: October 2019

Abstract
The CD15 antigen is an adhesion molecule normally expressed on neutrophils that mediates phagocytosis and chemiotaxis: it is also expressed on blasts of patients with acute myeloid leukemia (AML). Its prognostic role has been tested in different studies, including or not acute promyelocytic leukemia (APL), with conflicting results and its significance still remains unclear. To address this issue, a cohort of 460 AML patients of all ages with, the exclusion of APL, [M/F 243/217, median age 50.6 years (range 0.9 – 81.2)] intensively treated at our Institute between 1/1999 and 12/2010 was retrospectively evaluated. Overall, 61 patients (13.3%) evolved from a documented myelodysplastic phase (MDS): AML-ETO, CBFβ-MYH11, FLT3-ITD and NPM were positive in 35/438 (8.2%), 30/427 (7.0%), 55/409 (13.4%) and 67/200 (14.6%) evaluable patients, respectively. A favorable karyotype was found in 90/436 patients (20.6%) while an unfavorable profile was documented in 60/436 cases (13.8%). CD15 positivity was found in 171/406 evaluable patients (42.1%): in particular, CD15 was positive in 13/42 evaluable patients evolved from MDS (31.0%) compared with 158/364 evaluable patients without previous MDS (43.4%) (p=0.123). Induction treatments consisted of anthracycline (ACY) + cytarabine (Ara-C) +/- etoposide in 448 patients and of a fludarabine-based regimen in 12 patients. A complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6 – 176.0), with a 2-year disease-free survival (DFS) rate of 45.1% (95% CI 39.6 – 50.6). The median overall survival (OS) was 14.4 months (range 0.3 – 177.0), with a 2-year OS rate of 42.2% (95% CI 37.5 – 46.9). Among the several variables tested at univariate analysis for CR achievement, age <60 years (p<0.001), WHO classification (p=0.045), low-risk karyotype (p<0.001), no high-risk karyotype (p=0.006), positivity for AML-ETO (p=0.004)/CBFβ-MYH11 (p=0.003)/CD15 (p=0.006)/CD11b (p=0.013), negativity for FLT3-ITD (p=0.001), Hb >8 g/dl (p=0.020) and WBC <50 x 109/l (p=0.034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (p=0.002 – OR 2.96,95%CI 1.51 – 5.89), age <60 years (p=0.008 – OR 2.28, 95%CI 1.23 – 4.21), WBC <50 x 109/l (p=0.017 – OR 2.34, 95%CI 1.16 – 4.73) retained an independent prognostic role on CR achievement. In conclusion, the baseline assessment of CD15 positivity could have a role in the risk evaluation for CR achievement in non-APL AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biological features already reported.

Disclosures
Breccia: novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Latagliata:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Shire: Consultancy.