Clinical Features and Outcome of 148 Patients with Acute Promyelocytic Leukemia in Brazil.
Authors: Jácomo Rafael H. , Melo Raul , Souto Fernanda , Mattos Éderson , Oliveira Claudia , Fagundes Evandro , Bittencourt Rosane , Bortolheiro Teresa , Paton Eduardo , Bendlin Rodrigo , Ismael Sebastião , de Lourdes Chauffaille Maria , Silva Dirceu , Ribeiro Raul , Rego Eduardo M. 
Published: October 2019

Abstract
Acute Promyelocytic Leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) which has a high prevalence in Latinos as well as a different distribution of PML breakpoints with a higher incidence of bcr1 isoform. We describe here the characteristics and outcome of 148 consecutive patients, from 11 centers in Brazil. Induction consisted of ATRA and anthracyclines (ida or daunorubicin). All centers used anthracyclines in consolidation but association with AraC was variable. Maintenance was based on low dose chemotherapy, except in 2 centers, which were excluded from survival analysis. The incidence of APL among AML was 28.2%. According to the risk stratification from PETHEMA/GIMEMA groups, 58 (39.2%) patients were classified as high risk (HR), 63(42.6%) as intermediate (IR) and 27 (18.2%) as low risk (LR), a higher frequency of HR patients than the reported by Sanz et al analyzing 217 APL patients (p=0.003). A relatively high frequency of early complications was observed, with 26 (17.6%) and 68 (45,9%) patients presenting with life threatening hemorrhage and disseminated intravascular coagulation (DIC), respectively. Early mortality (death in the first 14 days of diagnosis) was higher than the described in developed countries - 42 (28.4%) patients; bleeding (37 patients) was the leading cause. Both early mortality and bleeding were more frequent in the HR group (p=0.002 and <0.001 respectively). From 106 patients alive at D+15, 88 patients survived induction and 73 were alive and in remission after consolidation. One patient relapsed before finishing consolidation and six were still in induction. There was no difference among risk groups in mortality after day 14 of induction. Mean overall survival (OS) for the 133 patients available for analysis was 614 days (CI95% 515–712). Excluding early mortality, mean OS was 844 days (CI95% 741–948). Mean OS was different among the risk groups - 928(785–1071), 748(598–898) and 313(187–439) days for LR, IR AND HR, respectively (p<0.001). Our data suggest that risk classification, besides identification of relapse probability, can identify patients with higher incidence of bleeding, laboratorial DIC and also those that are predisposed to death secondary to hemorrhage and this may alert to the necessity of a more intensive supportive care in induction for this group. Despite the fact that ATRA and anthracyclines are available in Brazil hospitals, these results show that Brazilian patients have a worse outcome than the reported by the latest trials. It is possible that late referral partially accounts for an increased number of high-risk APL among these Brazilian patients. Hence, in addition of specific drugs availability, prompt access to care and initiation of specific therapy is necessary to improve outcome. In this regard, the International Consortium in APL (IC APL), created in 2005 by the International Committee of the American Society of Hematology, aims to implement a network to allow the exchange of experiences among hematologists in developing countries and international specialists as well as to offer real time discussion of newly-diagnosed patients with APL and ongoing complications.