Prognostic Impact of the Amount of CD34+ CD38- CD123+ Cells at Diagnosis In Acute Myeloid Leukemia: a Study From the GOELAMS
Authors: Vergez François , Green Alexa , Tamburini Jérôme , Gallay Nathalie , Roussel Murielle , Gaillard Baptiste , Neyret Aymeric , Pannetier Melanie , Chapuis Nicolas , Ifrah Norbert , Dreyfus Francois , Demur Cécile , Lacombe Catherine , Mayeux Patrick , Bouscary Didier , Manenti Stéphane , Récher Christian , Bardet Valérie 
Published: October 2019

Abstract
Abstract 951
AML cells with CD34+CD38-CD123+ phenotype represent a subset enriched in leukemic stem cells. Moreover, this subpopulation has been described to be resistant to genotoxic agents as compared with leukemic bulk. However, the clinical impact of the amount of CD34+CD38-CD123+ remains poorly described. In this study we evaluated the prognostic impact of the amount of CD34+CD38-CD123+ cells detected at diagnosis in a series of AML patients treated by intensive chemotherapy according to trials from the French GOELAMS group.
Quantification of blast cells with the CD34+CD38-CD123+ phenotype was achieved by flow cytometry in 111 patients less than 66 years old with de novo AML treated by 3+7-like chemotherapy.
The characteristics of the patients are shown in table 1.
Age, WBC count, NPM1 mutation and FLT3-ITD had no impact on achievement of complete response (CR) whereas, CD34+CD38-CD123+ (>15%) and unfavourable karyotype were significantly correlated with lack of CR. By logistic regression, CD34+CD38-CD123+ (>15%) retains significance for CR achievement with an OR of 0.3 (0.11-0.84) (p=0.02). For the 91 complete responders, age, WBC count, karyotype, NPM1 mutation had no impact on disease-free survival (DFS).Interestingly, patients with <1%, 1–15%, >15% CD34+CD38-CD123+ had a median DFS of 57.6 (SE 6.6), 11.2 (SE 7.5) and 9.2 (SE 13.4) months, respectively (p<0.0001, figure 1). FTL3-ITD was also significantly associated with a shorter DFS. In multivariate analysis, CD34+CD38-CD123+<1% was significantly associated with a longer DFS (p=0.00025). Age, %CD34+CD38-CD123+, karyotype, NPM mutation and FLT3-ITD significantly influenced overall survival (OS) whereas WBC count had no impact. Median OS was particularly impressive for patients with CD34+CD38-CD123+<1%. Indeed, median OS was 78.2 (SE 10.7), and 15.3 (SE 5.8) months for CD34+CD38-CD123+<1% vs others, respectively (p<0.0001, figure 1). Multivariate analysis for OS retains two significant factors: adverse karyotype (95%CI, 1.19–4.02, p=0.012) and CD34+CD38-CD123+<1% (95%CI, 0.12–0.52, p=0.00018). Moreover, although the number of patients was low in favourable karyotype (CBF), CD34+CD38-CD123+<1% had a major impact on both DFS, median 57.6 vs 10.2 months for >1% (HR, 0.19, 0.06–0.59, p=0.0038) and OS, median not reached vs 18.5 months (p=0.0025).
This study emphasizes the prognosis impact of the CD34+CD38-CD123+ cell burden in AML patients, which is predictive for shorter OS and DFS when representing more than 1% of the leukemic cells, regardless of the usual prognosis categories. We provide here a new prognosis marker that may be easily translated to the clinical practice in AML although it remains to be validated on a large prospective cohort of patients. Moreover, new therapies targeting this subpopulation could help to improve outcome in AML patients.TableCharacteristics of patients.All patients N=111CD34+CD38-CD123+< 1 % N=40CD34+CD38-CD123+ 1-15% N=20CD34+CD38-CD123+> 15% N=20Gender, M/F50/6219/2124/276/14Age, median48 (20–65)47 (20–65)51 (20–64)50 (21–65)WBC,median (G/L)33.2 (1–254)13.8 (1–237.7)41 (1.3–254)32.9 (2.3–193.2)Favourable caryotype231184Intermediate caryotype6924378Unfavourable caryotype19568NPM1 mutation28/957/3116/455/19FLT3-ITD33/1007/3421/475/19Complete Response91 (82%)36 (90%)42 (81.4%)13 (65%)Relapse53 (58.2%)13 (36.1%)30 (71.4%)10 (76.9%)Allogeneic-SCT33 (36.3%)11 (30.6%)15 (35.7%)7 (53.8%)

Disclosures:
No relevant conflicts of interest to declare.