Prognostic Impact of High Hematogones in Acute Myeloid Leukemia
Authors: Pereira Dulcineia , Chacim Sergio Pereira , Mesquita Edgar , Espirito-Santo Ana , Moreira Ilidia , Domingues Nelson , Oliveira Isabel , Viterbo Luísa , Marques Margarida , Palmeira Carlos , Sousa Maria Emília , Godinho Inês , Pires Ana Marta , Cerveira Nuno , Bizarro Susana , Teixeira Manuel R. , Martins Ângelo , Martins Gabriela , Mariz Jose Mario 
Published: October 2019

Abstract
Abstract 1435

Introduction:
The response to AML treatment is very heterogeneous and relapse risk is high. Hematogones (HG) are B lymphoid cell precursors present in all individuals. HG absolute count grows after chemotherapy, during medullar recovery and it seems to be related to prognosis.

Objectives:
Determination of HG number in AML patients with intermediate-risk karyotype, with complete response (CR). Determine prognostic value for HG number in these patients.

Methods:
Retrospective analysis of 148 patients with non promyelocytic AML, treated with “7+3” chemotherapy induction, followed in our centre, from 1998 to 2011. HG quantification was executed after induction chemotherapy, with flow cytometry pannel (4 colours - CD34, CD10, CD19, CD20 e CD45) in blood marrow samples in patients with CR, according to Cheson et al. (JCO 2003). The patients characteristics were compared with a X2test for binary variables and a Mann-Whitney test for continuous variables. Survival was plotted with Kaplan-Meier curves and the data for the various groups were compared with a log-rank test. Multivariate analysis was performed with a Cox model after the proportional hazard assumption was checked. A p value less than 0.1 was considered to be statistically significant.

Results:
There were 124 patients achieving CR after induction chemotherapy “7+3”, with a median follow up of 32 months ([0–141]), 46,8% (n=58) were male, median age of 50 years ([17–66]). There were 91,1% (n=113) patients with de novo AML and 63,9% (n=76) with intermediate-risk karyotype. In this study 16,3% (n=20) went on transplantation. Relapse occurred in 53,2% (n=66), with a disease free survival (DFS) of 15 months ([0–140]). HG quantification was possible in 33,1% (n=41) of the patients. Applying a cutoff of 0.01% (Chantepie S et al. Blood 2011) we can find 31,7% (n=13) with HG>0.01%. These patients had better DFS, when comparing to patients with HG≤0.01% (median 16 vs 9 months, p=0,05), to equal overall survival.
According to multivariate Cox model, the HG>0,01% is a independent predictive value for DFS (IC 95% [0,8533-54.259], p<0,07), when comparing to HG≤0,01%, age, leucocytosys (>20000/μL), karyotype-risk groups and WHO classification of AML. We established a good prognosis associated to HG>0,01% group: patients with HG≤0,01% have a 6.8 hazard ratio (HR) or relapse comparing with HG>0,01% group. Considering this information and applying it to karyotype-intermediate risk patients, it was possible to obtain two different groups with prognostic impact on the DFS: low intermediate risk (HG>0,01%) and high intermediate risk (HG<0,01%).The 3 year-DFS is 83,3% for low intermediate risk group and 50% for high intermediate risk patients (p<0,094).

Conclusion:
Using flow cytometry is a simple and reproductively method for detecting HG. This quantification in AML patients with CR has clinically relevance, with prognostic impact in DFS (16 vs 9 months, p=0,05). For HG levels superior to 0,01% after induction chemotherapy the risk of relapse is decreased. The HR associated to HG value allowed the stratification of the intermediate-risk group in two subgroups of patients (low intermediate risk group and high intermediate risk patients) with different DFS (83.3% vs 50% 3-y EFS, p<0,094). This subdivision can have implications on clinical decision for therapeutic strategy, in the heterogeneous intermediate-risk karyotype group. This cohort needs to be enhanced in order to validate this approach.

Disclosures:
No relevant conflicts of interest to declare.