PF290 INCIDENCE AND PROGNOSTIC IMPACT OF A BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM‐LIKE PHENOTYPE IN AML PATIENTS
Authors: Guolo F. , Minetto P. , Clavio M. , Ballerini F. , Kunkl A. , Tedone E. , Contini P. , Mangerini R. , Cagnetta A. , Cea M. , Gobbi M. , Miglino M. , Lemoli R.M. 
Published: June 2019

Background:Blastic plasmacytoid dendritic cell neoplasms (BPDCN) are rare disorders included by WHO 2016 classification among the myeloid neoplasms and characterized by aggressive clinical course and dismal outcome. BPDCN display a recurrent phenotype (CD45low/CD34‐/CD56+/CD4+/CD123+), in the absence of lineage differentiation. Our group recently reported a negative prognostic impact of CD123, CD56 and CD4 co‐expression (“BPDCN‐like” phenotype) in AML patients with NPM1‐mutation.Aims:The aim of the present study was to evaluate the incidence and the prognostic impact of BPDCN‐like phenotype in a wider cohort of cytogenetically normal AML patients, irrespectively of NPM1‐mutational status.Methods:We retrospectively evaluated a cohort of 83 younger (age <60 yrs), consecutive AMLpatientswith normal karyotype, who have been intensively treated in our institution between 2006 and 2016. All patients were treated with the same fludarabine‐idarubicin‐Ara‐C containing induction. In all patients, four (until 2012) or eight color immunophenotypic analysis has been performed at diagnosis. We defined a BPDCN‐like signature as the combination of at least two among CD56+/CD4+/CD123+ and evaluated its prognostic impact as well as the correlation with biological, molecular and cytogenetic features.Results:Fifteen patients (18%) showed a BPDCN‐like signature. Neither the presence of NPM1‐mutation nor FLT3‐ITD or biallelic CEBPA mutation had a significant correlation with BPDCN‐like signature. BPDCN‐like patients had significantly higher WBC count at diagnosis (p < 0.05). No clear correlation with sex or age at diagnosis was observed. In the whole cohort of patients, only the presence of NPM1‐mutation correlated with the achievement of complete response (CR).Median follow‐up was 63 months, 3‐year Overall Survival (OS) was 52% in the whole cohort (median 38 months). Patient with NPM1 mutation or biallelic CEBPA mutation had a better outcome (p < 0.03). OS was not significantly influenced by the FLT3‐ITD mutation or by the presence of BPDCN‐like signature.However, as we previously reported, in the subgroup of 30 patients with NPM‐1 mut AML, the presence of BPDCN‐like features conferred a dismal prognosis (3‐year OS 25% vs 77% for BPDCN positive and negative patients, respectively, p < 0.001), irrespectively of mutational status for FLT3‐ITD or other clinical features. Even if CR rate was not affected, all NPM1‐mut patient with BPDCN‐like phenotype failed to achieve minimal residual disease (MRD)‐negative CR (p < 0.05).On the contrary the negative prognostic influence of BPDCN‐like phenotype was not observed in the 53 NPM‐1 wt patients (3‐year OS 71% vs 35% for BPDCN‐like positive and negative NPM‐wt patients, respectively, p = 0.156). No difference in MRD clearance probability was observed in this subgroup.Summary/Conclusion:Our extended analysis confirms that a peculiar BPDCN‐like immunophenotype among NPM‐1 mut AML patients is associated with significantly worse outcome in this otherwise favorable subset of AML. Patient with BPDCN‐like features, even if achieving morphological CR showed high level of minimal residual disease after induction, suggesting an intrinsic chemo‐resistance. Interestingly, this observation was strictly restricted to NPM‐1 mutated AML, suggesting that peculiar alterations in this distinct entity contribute to the prognostic impact of BPDCN‐like features in this setting.imageThe biological explanation of this finding is not clear; further gene‐expression profiling studies are ongoing in order to explain our findings.