A Simple Clinical Prognostic Scoring System for Newly Diagnosed Cytogenetically Normal Acute Myeloid Leukemia: a Retrospective Analysis on 530 Patients
Authors: Malagola Michele , Skert Crisitina , Vignetti Marco , Piciocchi Alfonso , Martinelli Giovanni , Mecucci Cristina , Testoni Nicoletta , Iacobucci Ilaria , Clavio Marino , Gobbi Marco , Anna Candoni , Damiani Daniela , Bocchia Monica , Lauria Francesco , Zaccaria Alfonso , Mazza Patrizio , Visani Giuseppe , Annalisa Peli , Mancini Marco , Foà Robin , Martelli Massimo , Cantore Nicola , Raimondo Francesco Di , Petrini Mario , de Fabritiis Paolo , Fioritoni Giuseppe , Nobile Francesco , Fabbiano Francesco , Specchia Giorgina , Baccarani Michele , Coco Francesco Lo , Amadori Sergio , Mandelli Franco , Russo Domenico 
Published: October 2019

Abstract
Abstract 4848

Objectives:
the prognosis of patients with cytogenetically normal acute myeloid leukemia (CN-AML) is highly variable and can be influenced by several clinical and biological variables. Nevertheless, some biological data may be conflicting and difficult to combine with the clinical ones.

Methods:
in order to propose a simple scoring system, we retrospectively analysed the clinical data of 337 patients newly diagnosed with CN-AMLs, aged less than 65 years, consecutively treated in eleven hematological Italian Centres from 1990 to 2005. Two hundred nineteen patients (65%) received a fludarabine-based induction regimen. All the other patients received a conventional induction regimen, including cytarabine, one anthracycline with or without etoposide. Univariate and multivariate analysis on event free survival and overall survival (EFS and OS) were performed. Patients addressed to allogeneic stem cell transplantation were censored at the time of transplant. Factors found to be significant in univariate analysis were tested in multivariate analysis. A numerical score was derived from the regression coefficients of each independent prognostic variable. The Prognostic Index Score (PIS) for each patient was then calculated by totalling up the score of each independent variable. Patients could thus be stratified into low-risk (score = 0–1), intermediate-risk (score = 2) and high-risk group (score grater than 3). The score obtained in this group of patients (training set) was then tested on 193 patients with newly diagnosed with CN-AMLs, aged less than 65 years, enrolled in the GIMEMA LAM99p clinical trial (validation set).

Results:
the clinical variables that were independent prognostic factors on EFS in the training set of patients were: age > 50 yrs (regression coefficient: 0.39, HR 1.5, score = 1), secondary AML (regression coefficient: 0.90, HR 2.5, score = 2) and WBC > 20 × 10^9/L (regression coefficient: 0.83, HR 2.3, score = 2). For what concerns the OS, the same variables showed the followings statistical data: age > 50 yrs (regression coefficient: 0.48, HR 1.6, score = 1), secondary AML (regression coefficient: 0.99, HR 2.7, score = 2) and WBC > 20 × 10^ 9/L (regression coefficient: 0.87, HR 2.4, score = 2). In the training set of patients, the median EFS was 22, 12 and 8 months in the low, intermediate and high-risk group (p<0.0001). The median OS was not reached in the low-risk group and was 20 and 10 months in the intermediate and high-risk group (p<0.0001). In the validation set of patients, the median EFS was 66, 16 and 3 months in the low, intermediate and high-risk group (p<0.0001). The median OS was 66, 16 and 4 months in the low, intermediate and high-risk group (p<0.0001).

Conclusions:
this simple and reproducible prognostic score may be useful for clinical-decision making in newly diagnosed patients with CN-AMLs, aged less than 65 yrs. Moreover, it can be clinically useful when the molecular prognostic markers are lacking (e.g. in emerging laboratories of some developing countries) or give contradictory results.

Disclosures:
No relevant conflicts of interest to declare.