Incidence and Characteristics of Acute Promyelocytic Leukemia in Adult Patients. A Single Centre Registry Study.
Authors: Montesinos Pau , Martin Guillermo , Martinez Jesus , Perez-Sirvent Mariluz , Sanz Jaime , Lorenzo Ignacio , Mendoza Ninotchka , Algarra Lorenzo , Sempere Amparo , Cervera Jose , Sanz Guillermo , Jarque Isidro , de la Rubia Javier , Cantero Susana , Palau Javier , Senent Leonor , Martinez David , Moscardo Federico , Sanz Miguel 
Published: October 2019

Abstract
Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by specific morphological and clinical features. However, its relative incidence among patients with AML is not yet established.
Objectives:
To define the relative incidence of APL in a large series of patients diagnosed with AML in a single institution and to identify the clinical-biological features characterizing the APL patients within the target population of AML.
Methods: From 1976 to 2007, 1205 patients (median age 56 years, range 15–98) were consecutively diagnosed with AML in our institution. One hundred patients (8%) were considered AML secondary to solid neoplasia or chemotherapy, while 143 (12%) were secondary to myelodysplastic or myeloprolypherative syndromes (MDS/MPCS). The APL diagnosis was achieved through cytological studies supported by cytogenetics, and since 1995 by molecular techniques. Inmunophenotype analysis, using flow cytometry or inmunohistochemistry, was available in 808 (67%) patients. Positivity was defined as more than 20% blasts expressing a specific antigen.
Results: Overall, 170 patients (14%) were diagnosed of APL. Of them, 43 (25%) were classified as M3 variant. The relative incidence of APL within AML secondary to solid neoplasia or chemotherapy and de novo AML was 13% y 16%, respectively (p=ns). In contrast, the relative incidence of APL within AML secondary to MDS/MPCS was 0.7% (p<0.0001) (only 1 case of APL secondary to MDS/MPCS was registered). The median age of APL patients was 44 years, and its relative incidence decreased with older age: 26% between 15 and 50 years, 12% between 51 and 60, 8% between 61 and 70, and 5% in older than 70 (p<0,0001). The percentage of APL patients receiving induction was higher compared with the rest of AML (93% vs 79%, p<0,0001). The complete remission rate was higher in APL (72% vs 53%), due to a lower resistance (3% vs 22%, p<0,0001), whereas the induction mortality was similar (25% vs 25%). The frequency of causes of death were different in APL compared with the rest of AML: hemorrhage (59% vs 22%), infection (27% vs 56%), hemorrhage and infection (8% vs 6%) and other (6% vs 16%). APL was associated with the following clinical-biological features: presence of Auer rods (80% vs 27%, p<0,0001), peroxidase positive blasts >75% (94% vs 27%, p<0,0001), bone marrow blasts >70% (92% vs 49%, p<0,0001), WBC <10x109/L (70% vs 48%, p<0,0001), LDH <600 U/L (68% vs 58%, p=0,003), uric acid <7,5 mg/dL (96% vs 87%, p=0,002), fibrinogen <170 mg/dL (53% vs 3%, p<0,0001), hemorrhagic syndrome at diagnosis (84% vs 32%, p<0,0001), lack of hepatosplenomegaly (12% vs 24%, p=0,001). APL was significantly associated with the following surface or cytoplasmatic antigens: CD34 negative (−), CD36(−), HLA-DR(−), CD14(−), CD4(−), CD56(−), TdT(−), CD11b(−), CD7(−), CD2 positive (+), CD9(+), CD33(+), CD71(+), CD117(+) and myeloperoxidase(+).
Conclusion: In this large series of patients diagnosed with de novo or secondary AML, the relative incidence of APL was 14%, being exceptional the APL secondary to MDS/MPCS. To our knowledge, this is the larger hospital registry establishing the relative incidence of APL in a target AML population.