Page 96 - Haematologica - Vol. 105 n. 6 - June 2020

F. Stölzel et al.
Prevalence and sites
Total body 18FDG-PET/CT imaging detected highly metabolic manifestations suggestive of EM AML in 23% of the enrolled patients (n=21). Of these 18FDG-PET posi- tive patients, 11 (52%) had de novo AML, while 7 (33%) had tAML and 3 (14%) secondary AML with preceding MDS/MPN. In total, 65 EM AML manifestations were identified with 18FDG-PET/CT in these 21 patients. The median SUVmax was 6.1 (range, 2-51.4). Patients with EM AML as per 18FDG-PET/CT had a median of two EM AML manifestations (range, 1-12) with only six patients having only one EM AML manifestation; exemplary 18FDG- PET/CT imaging is depicted in Figures 2A and B and 3A and 3B. Sites of EM AML as detected per 18FDG-PET/CT were connective tissue (n=4, one patient paravertebral, one paraaortic, one next to the jaw angle, and one at the base of the tongue), parenchymal tissues (n=8, with man- ifestations in adrenal glands, kidneys, liver, and spleen), and lymph nodes (n=15). A total of 9% of patients pre- sented with clinically overt EM AML (n=8). Applying 18FDG-PET/CT, additional EM manifestations were detected in 62% (n=5) of these patients. In 12 of the 21 patients who were diagnosed with EM AML as per 18FDG- PET/CT, biopsies from EM sites were obtained in order to assess the provenance of the diagnosed tumor and to assess the sensitivity of 18FDG-PET/CT. In ten patients, histology review confirmed the occurrence of EM AML in these sites, indicating a sensitivity of 77% for 18FDG- PET/CT. Interestingly, in the two remaining patients in whom histology could not confirm EM AML, concomi- tant tumors were found (one patient with Castleman’s disease and one patient with a solid fibrous tumor). Extrapolating these results onto the entire cohort, and applying the positive predictive value of 83.3%, the preva-
lence of EM AML in our AML patient cohort was 17% (95%CI: 11-29%). When only analyzing patients with newly diagnosed AML, 16 (19%) patients were identified with EM AML as per 18FDG-PET/CT. Characteristics of patients with or without EM AML as per 18FDG-PET/CT and histological confirmation are shown in Online Supplementary Table S1. In comparison with PET-negative patients, those with PET-positive EM AML as per 18FDG- PET/CT had a higher percentage of bone marrow infiltrat- ing blasts, higher white blood cell (WBC) count in the peripheral blood, and higher C-reactive protein serum lev- els. Furthermore, in the cohort of AML patients with EM disease, there were no patients with favorable cytogenetic risk and a higher fraction of patients with relapsed AML.
In addition, in three patients of the 18FDG-PET/CT neg- ative group (n=72), EM AML was identified on examina- tion and diagnosed through histological confirmation after biopsy. Two of these patients had a skin manifestation (chloroma) while one patient developed cervical lym- phadenopathy during induction chemotherapy and then underwent biopsy and an additional, unscheduled 18FDG- PET/CT, both confirming the diagnosis of EM AML. When these patients were added to our extrapolated prevalence of EM AML, the combined prevalence of EM AML in this study was 22%. Thus, the specificity for 18FDG-PET/CT to detect EM AML is 97%. An overview of patients undergoing biopsy for diagnosis in both cohorts is available in the Online Supplementary Table S2. When we analyzed only the largest subgroup of our study cohort of patients with newly diagnosed AML, the combined preva- lence of EM AML was 17%.
A total of 18 patients (19%) in this study were treated with hydroxyurea prior to 18FDG-PET/CT and thus prior to initiation of chemotherapy. Four of the 21 patients
Figure 1. Modified CONSORT diagram demon- strating screening, patient selection and analysis for the complete patient cohort. PETAML: PET-CT in AML for Detection of Extramedullary AML Manifestations study; n: number; 18FDG-PET/CT: 18Fluorodesoxy-glucose positron emission tomogra- phy/computed tomography; EM: extramedullary; AML: acute myeloid leukemia.
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