Identification of Prognostic Immunophenotypes at First Diagnosis in Patients with Acute Myeloid Leukemia (AML) By a Standardized Multicolor Flow Cytometry (MFC) Panel Originally Designed to Detect Measurable Residual Disease (MRD) at Follow-up

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.35-35
• Main Authors: Rohnert, Maximilian Alexander A, von Bonin, Malte, Kramer, Michael, Ensel, Philipp, Holtschke, Nadja, Rollig, Christoph, Bornhäuser, Martin, Buecklein, Veit, Subklewe, Marion, Krause, Stefan W, Voelkl, Simon, Berg, Tobias, Rieger, Michael A, Brendel, Cornelia, Hoffmann, Jörg, Hofmeister-Mielke, Nicole, Schlenk, Richard F., Freeman, Sylvie D, Oelschlägel, Uta
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-138683

Aims In AML, several risk factors obtained at first diagnosis (FD) have been reported to be associated with shorter RFS and OS. The primary prognostic relevance of multicolour flow cytometry (MFC) has been a matter of debate for years. During follow-up (FU), the prognostic relevance of MRD as detected by MFC is less controversial and MFC is recommended in particular (but not exclusive) for those patients (pts) with no reliable genetic marker. We thought to evaluate the prognostic value at FD of a recently established antigen panel and a corresponding analysis strategy, which had been originally developed for MRD-detection. Methods Based on an 8-colour antibody panel (CD45, CD34, CD117, HLA-DR, CD13, CD33, CD7, CD56), we have developed a hierarchical gating strategy with mainly fixed gates. That allows to detect MRD with a high level of standardization and inter-observer reliability (Röhnert M., et al. 25th EHA 2020). Four distinct categories of aberrations (deficiency of CD13 or CD33, cross-lineage expression of CD7 or CD56) detectable on at least 10% of the myeloid blast population were used to define aberrant phenotypes termed leukemia associated immunophenotypes (LAIP) at FD. These categories were also chosen to define MRD during FU. MRDpos by LAIP was defined as the (re-)occurrence of an aberrant category already detectable at FD, while MRDpos by DfN (different from normal) was defined by the de-novo detection of an aberrant category at FU. The prognostic value of the aberrant phenotypes at FD was examined in a cohort of 528 pts. In 122 pts, we further analysed MRD (LAIP/DfN) after completion of intensive induction chemotherapy (IT). Consolidation therapy consisted of allogeneic hematopoietic stem cell transplantation (n=77) or chemotherapy (n=45). The bone marrow samples were measured centrally and analysed independently by three different investigators. Results The probability to achieve a complete remission (CR) varied between the different aberrant phenotypes (LAIP) at FD. Compared to pts without aberrant phenotype (CR rate=68%, n/N=100/148), pts with CD56only (the sole aberrant category was a cross-lineage expression of CD56=only) had a significantly lower CR rate (46%, n/N=15/33, p=0.019). The other exclusive aberrant categories did not significantly influence CR rates compared to pts without LAIP: CD13only (75%, n/N=53/71, p=0.286), CD33only (64%, n/N=59/97, p=0.28) and CD7only (62%, n/N=31/50, p=0.472). In pts with possibly co-occurring aberran