Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial

Abstract

Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients р65 years and with initial WBC counts below 5000/mm 3 were randomized between ATRA until CR achievement followed by CT (ATRA → CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA → CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA → CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome.

Retinoid-induced activation of NF-κB in APL cells is not essential for granulocytic differentiation, but prolongs the life span of mature cells

“…ATRA-induced differentiation on APL cells results in the activation of several leukocyte functions, including expression of adhesion molecules and secretion of cytokines. These events allow myeloid precursors and mature granulocytes to infiltrate several organs, and are believed to be involved in generation of the retinoic acid syndrome (RAS), which remains the major side effect of ATRA and can lead to fatal outcome (De Botton et al, 1998;Tallman et al, 2000;Larson and Tallman, 2003). Until now, the best approach to treat patients with RAS is early identification of the symptoms and administration of dexamethasone (Larson and Tallman, 2003).…”

Características hematológicas e perfil de expressão de antígenos mielóides de pacientes com leucemia promielocítica aguda: análise de fatores prognósticos para o desenvolvimento da síndrome do ácido retinóico

“…A incidência da SAR na literatura variou entre 6% a 27% [15][16][17]19,29 , refletindo as diferenças quanto à associação ou não de antracíclicos e quanto ao momento de sua introdução. No presente estudo, a incidên-cia da SAR foi de 11,26%, semelhante à descrita por De Botton et al 17,30 usando o mesmo protocolo de tratamento. A importância da introdução do antracíclico nos primeiros dias do tratamento com ATRA na prevenção da SAR foi estudada pelo Grupo Europeu para o Estudo da LPA, o qual encontrou uma incidência da SAR de 18% no grupo de pacientes que recebeu quimioterapia após o uso prolongado de ATRA (até a obtenção de remissão), em contraste com uma incidência de apenas 9,2% no grupo que recebeu a mesma a partir do 3 o dia do tratamento 30 .…”

“…Ademais, a mortalidade por SAR foi menor no segundo grupo (0,5% versus 2,5%). Em relação à mortalidade, esta variou entre 0,5% e 29%, embora estudos mais recentes tenham observado índices inferiores a 10% 16,19,30,31 . Assim, a mortalidade observada no presente estudo (25%) foi elevada, o que não parece decorrer do tratamento usado, uma vez que o mesmo (administração de dexametasona em altas doses) foi semelhante àquele adotado por Frankel et al 15 e por Vahdat et al 19 que descreveram percentagens de óbito em pacientes com SAR de 4,5% e de 5,25%, respectivamente.…”

Retrospective analysis of 119 cases of pediatric acute promyelocytic leukemia: Comparisons of four treatment regimes

“…It develops rapidly and is potentially fatal. Upon observation of the earliest signs of retinoic acid syndrome, treatment with high-dose steroids was initiated immediately by administering dexamethasone at 0.3 mg/kg/dose twice daily intravenously for at least 4 days to the children (22). In addition, hydroxyurea was administered to control leukocytosis when required.…”