Leucemia promielocítica aguda: avaliação retrospectiva dos casos diagnosticados e tratados pelo serviço de hematologia do hospital universitário da Universidade Federal de Santa Catarina entre 2001 a 2013

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2014.A leucemia promielocítica aguda (LPA) é um subtipo distinto de leucemia mieloide aguda (LMA), caracterizado pela presença de um acúmulo de promielócitos anormais na medula óssea e/ou sangue periférico, com risco de coagulopatia e a presença da translocação recíproca e balanceada entre os cromossomas 15 e 17 t(15;17)(q22;q12) e variantes. Nos últimos anos, o curso clínico da LPA tem sido modificado de uma leucemia aguda rapidamente fatal para um dos subtipos de LMA mais curáveis. A introdução de agentes terapêuticos que atuam diretamente na alteração molecular, como o ácido all-trans-retinóico (ATRA) e o trióxido de arsênico (ATO), tiveram um grande impacto na sobrevida dos pacientes com LPA. O diagnóstico presuntivo de LPA deve ser rápido, pois os pacientes correm risco de morte precoce. A incidência da LPA no Brasil é maior (20%) que nos Estados Unidos e Europa Ocidental (5 a 15%). As elevadas taxas de mortalidade, especialmente a mortalidade precoce, fazem com que estudos sejam feitos para o melhor entendimento dessa doença no nosso contexto. Alguns fatores de prognóstico adverso conhecidos têm sido usados como guia de intensificação de tratamento, tais como, o critério de Sanz (2000), o qual se baseia na plaquetopenia (10x109/L). Porém, ainda se estudam fatores prognósticos adicionais que podem interferir negativamente no curso da doença, a citar: a expressão do CD34 por imunofenotipagem, alto valor da desidrogenase láctica (LDH), mutações no gene do FLT3, hemorragia grave, alto score de coagulação intravascular disseminada (CIVD), anemia (hemoglobina Abstract : Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) characterized by the accumulation of abnormal promyelocytes in bone marrow and/or peripheral blood, with risk of coagulopathy and chromosomal alterations involving the gene locus for the retinoic acid receptor alpha (RARa) associated in most of cases with reciprocal and balanced translocation between chromosomes 15 and 17 t(15,17)(q22;q12) and their variants. The clinical course of APL has been modified in recent years, from rapidly fatal acute leukemia to one of the curable subtypes of AML. The introduction of therapeutic agents that act directly on the molecular changes, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) had a major impact on APL patient survival, which is around 70-90%. The presumptive diagnosis of APL should be quick, because these patients are at risk for early death. The incidence of ALP in Brazil is higher (20%) than in the United States and Western Europe (5-15%). The slightly high mortality rates, especially early mortality, motivate studies to understand this pathology in the Brazilian context. Some known adverse prognostic factors have been used as a guide for intensifying the treatment, such as the criterion by Sanz (2000), which is based on thrombocytopenia (10x109/L). Nevertheless, additional prognostic factors are still being studied that can negatively impact the course of the disease, namely: CD34 expression, high value of lactate dehydrogenase (LDH), mutations in the gene FLT3, severe bleeding, high disseminated intravascular coagulation (DIC) score, anemia (hemoglobin<10g/dL), hipogranular APL, additional chromosomal abnormalities (ACAs), PML-RARa transcript bcr3. For this, it was analyzed retrospectively the laboratory and clinical findings of 44 patients with APL diagnosed and treated at the hematology service of the University Hospital of the Federal University of Santa Catarina (HU-UFSC) between 2001 and 2013. The according with results, the patients were classified following: risk group (PETHEMA system), performance status, coagulation disturbance, DIC score, and prognostic factors such, expression of CD34, FLT3 mutations, APL hipogranular, ACAs, value of hemoglobin,42LDH. The response of treatment was evaluated during induction, consolidation and maintenance, and the occurrence of relapse and death. APL corresponded to 25% of all AML cases in this study. Of the 44 patients studied, 37 (87.8%) had complete remission. Over two years, overall survival (OS), disease-free survival (DFS), event-free survival (EFS) and risk of hematologic relapse (RR) were 77.2%, 67.4%, 67.4% and 8.3%, respectively. Early mortality occurred in 15.9%, representing 78.9% of total APL deaths. The greatest cause of death was severe bleeding, especially in the central nervous system (CNS). In multivariate analysis with logistic regression, the prognostic factor influencing response to therapy were the absence of sepsis (p=0.007). The prognostic factor that most influenced death was severe bleeding (p