Haema 2017; 8(2): 212-227
by Maria N. Pagoni, Ioannis Tsonis, Chara Giatra
Haematology – Lymphomas Department and BMT Unit, Evangelismos Hospital, Athens, Greece
Abstract
The story of Acute Promyelocytic Leukemia (APL) is one of the most exciting in modern Haematology. It was first described as a distinct entity in 1957 and it was thought to be one of the most fatal forms of Acute Myeloblastic Leukemia, mainly due to serious bleeding events accompanying the diagnosis. Nowadays, APL is a paradigm for incorporating targeted therapies into clinical practice and it is considered a curable disease. APL diagnosis is initially based on patient’s history, physical examination, peripheral blood and bone marrow morphology, as well as haemostasis screening tests. Flow cytometry assays, cytogenetic studies (conventional karyotype or FISH) for reciprocal translocation t(15;17) and identification of the chimeric gene PML/RARA by molecular studies, confirm the diagnosis. In depth understanding of the pathogenetic mechanism of this disease in 1980s, resulted in a real revolution in therapeutic approach. It was then when a non-chemotherapeutic agent, all-trans retinoic acid (ATRA), was first used to treat such an aggressive malignant condition. ATRA as monotherapy demonstrated extraordinary remission rates, but unacceptable relapse rates. Studies on the efficacy of addition of chemotherapeutic molecules to ATRA showed that concomitant administration of ATRA+anthracycline±aracytin resulted in fewer relapses and a lower incidence of differentiation syndrome. Incorporation of arsenic trioxide (ATO) into the therapeutic armamentarium of APL followed in 1990s. A few years later synergistic action between ATRA and ATO was proven, through differentiation and apoptosis enhancement, and treatment with targeted and non-chemotherapeutic regimens was established. In addition, patient risk stratification provides rational approach and omission of chemotherapeutic agents, at least within the low risk group, as well as intensification of treatment in high risk patients, which is expected to eliminate long term complications, such as secondary malignancies, and relapse rates, respectively. In the near future, by means of further therapeutic advances, high risk patients are expected to be treated without chemotherapy, as well. Currently, cases of primary resistance are rare and overall survival rates are about 80% in high risk group and even better among low risk patients. Despite progress made on therapeutic approach for APL, there is emerge need to further reduce early death rate, which is still problematic. For this reason, ATRA initiation even with APL suspicion is of crucial importance, as this disease is still considered to be a medical emergency.