The results of the International Consortium on Acute Promyelocytic Leukemia: a 'proof of concept' of networking as a strategy to improve the outcome of treatment of hematological malignancies in developing countries

DOI: 10.5581/1516-8484.20130001 On January 14th 2013, the results of the International Consortium on Acute Promyelocytic Leukemia (IC-APL)(1) were published online in the journal Blood. Eight Brazilian institutions participated in the IC-APL: the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP) as coordinator, the Hematology Divisions of the Universidades Federal do Rio Grande do Sul (UFRGS), do Paraná (UFPR) and de Minas Gerais (UFMG), the Hematology and Transfusion Medicine Division of the Universidade Federal de São Paulo (UNIFESP), Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (UNICAMP), the Hematology Division of Santa Casa de São Paulo (SCSP) and Fundação Hemocentro de Pernambuco (HEMOPE). The IC-APL was developed under the auspices of the American Society of Hematology and gathered specialists from Latin America, the United States and Europe with the aim of improving the cure rates of patients with acute promyelocytic leukemia (APL) in developing countries through the establishment of an international clinical network. Four developing countries were selected to participate in the IC-APL: Brazil, Chile, Mexico and Uruguay; 183 adult patients with suspected diagnosis of APL were enrolled in this registered trial between June 2006 and September 2010. In order to participate in the IC-APL, countries had to fulfill minimum requirements, which included availability of drugs, pre-existing transfusion medicine services, a hematology lab capable of performing basic fluorescence microscopy and ability to report data and participate in meetings using web tools. APL was selected as a model disease to test the hypothesis that networking is an effective strategy to improve the outcome of patients with hematological malignancies in developing countries. The main reasons that guided this choice were: a) APL has become a highly curable disease since the introduction of combination therapy with alltrans retinoic acid (ATRA) and anthracycline-based chemotherapy, b) ATRA is of relatively low cost and available in the four developing countries, and c) the prompt diagnosis and immediate introduction of therapy can revert the coagulation abnormalities common in the disease and associated with high mortality rates due to bleeding. In order to perform a prompt diagnosis and the immediate introduction of ATRA, the ICAPL adopted the anti-PML immunofluorescence staining test which was developed by Falini et al.(2) and requires minimal infrastructure. This test is based on the molecular pathogenesis of APL, which is characterized by its association with chromosomal translocations involving the loci of the Promyelocytic Leukemia (PML) and Retinoic Acid Receptor Alpha (RARa) genes on chromosomes 15 and 17, respectively. The PML-RARA fusion protein retains most of the functional domains of the parental proteins and interacts with several proteins in the nucleus, in particular with the native PML causing its delocalization from the nuclear body(3). As a consequence, in APL cells, the PML protein is dispersed throughout the nucleus and generates a microspeckled pattern identifiable by the immunofluorescence staining test using the anti-PML (PG-M3) antibody (Figure 1).