Acute Promyelocytic Leukemia: An Experience on 95 Greek Patients Treated in the All-Trans-Retinoic Acid Era

Abstract

Acute promyelocytic leukemia (APL) is highly curable with the combination of all-transretinoic acid (ATRA) and anthracycline based chemotherapy, but the percentage of early deaths remains high. In the present study, we report the clinical, immunophenotypic, cytogenetic and molecular characteristics and outcome of APL patients diagnosed and treated in various Hospitals of Greece and Cyprus.We describe the data of ninety-five APL patients who were diagnosed during the last 15 years. Seven (7.4%) newly diagnosed APL patients died due to intracranial hemorrhage within 72 hours of presentation. All but two patients were induced with ATRA alone or ATRA plus chemotherapy. The early death rate was 14.9%. After induction all 80 evaluable patients achieved complete hematologic remission. The cumulative incidence of relapse was 18.3%. Eight of the ten relapsed patients were successfully salvaged, while both patients with molecularly resistant disease died during salvage treatment. Overall survival (OS) at 5 years was 78.4% and disease free survival (DFS) 73.6%. In multivariate analysis of OS age over 60 years, DIC at diagnosis and marginally major hemorrhage at presentation were identified as adverse prognostic factors. In the subgroup of patients with available data on FLT3 mutation status (49 out of 94), ITD positivity also remained as an independent prognostic factor in the final model of OS, together with major hemorrhage and marginally high Sanz score. We found a close correlation between the CD2 expression and the development of the differentiation syndrome (DS). In conclusion, the main problem in managing patients with APL is still the high early death rate.

Clinical characteristics, outcome and early induction deaths in patients with acute promyelocytic leukaemia: a five-year experience at a tertiary care centre

“…While a Turkish study reported a high incidence of early induction death at 40%, (20) a high early death rate of 32% was reported in a Brazilian study, (29) and a Greek study found early death rate to be 14.9%. (34) In another series, the early death rate among patients with APL was 21.5%. (35) These population-based studies suggest that the early death rates depicted in clinical trials do not correspond to real-life circumstances and have not changed much in the ATRA era, as seen in our study.…”

Characteristics and predictors of early hospital deaths in newly diagnosed APL: a 13-year population-wide study

“…ED rates ranging from 9.6% to 61.5%, depending on the population studied. [14][15][16][17][18][19][20][21][22][23][24][25][26][27] Efforts to develop international recommendations have led to a gradual improvement in ED rates over the past 3 decades, from 28% in the 1990s to $15% over the past 2 decades. [27][28][29] Major risk factors for ED include advanced age, high-risk disease, poor performance status, and coexisting infection.…”

Real-life outcomes of unselected acute promyelocytic leukemia patients: a single-center 14-year experience

“…Also, some trials have excluded patients from analyses if they die before receiving treatment [6]. On the other hand, in population-based analyses and single-center experiences from different countries, the rate of induction mortality rate is up to 61.5%, which is higher than expected [11][12][13][14]. Especially populationbased reports from the developed countries emphasize neither ED nor OS improved in the past two decades despite modern therapy methods [15][16][17].…”