RESUMO
We prospectively studied the efficacy and adverse effects of chlorpromazine (30 mg/m2 given intravenously) plus lorazepam (0.04 mg/kg given intravenously) versus chlorpromazine alone in a controlled, double-blind, randomized, parallel-design investigation in 25 children (1.5 to 17.3 years of age) with acute lymphoblastic leukemia. Response to other antiemetics in eight children refusing random assignment to treatment was also evaluated. All children were receiving intravenous infusions of teniposide plus cytarabine, the pharmacokinetics of which were characterized for each of the one to four courses. There were no differences between the 11 patients randomly assigned to receive chlorpromazine alone and the 14 randomly assigned to receive lorazepam plus chlorpromazine in the number of emesis episodes (6.0 vs 5.9; p = 0.53), frequency of dystonic reactions (3% vs 5%), or akathisia (13 vs 10%). The only serious adverse event, symptomatic hypotension, occurred in a boy receiving chlorpromazine plus lorazepam. An exploratory pharmacodynamic analysis revealed that the only variable that correlated with vomiting was cytarabine 1 1/2-hour plasma concentration (p = 0.007). Children who received either chlorpromazine plus lorazepam or chlorpromazine alone had fewer episodes of vomiting than those who received "conventional" antiemetic therapy (6.0 vs 8.6; p = 0.01). We conclude that the severity of emesis is related to the plasma concentration of cytarabine; that intravenously administered chlorpromazine is as effective as chlorpromazine plus lorazepam in preventing chemotherapy-induced vomiting; and that the potential for adverse effects with the addition of lorazepam may be a disadvantage.
Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Clorpromazina/uso terapêutico , Lorazepam/uso terapêutico , Vômito/prevenção & controle , Adolescente , Antieméticos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Clorpromazina/administração & dosagem , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Citarabina/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Lactente , Lorazepam/administração & dosagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão , Teniposídeo/administração & dosagem , Teniposídeo/efeitos adversos , Vômito/etiologiaRESUMO
In order to characterize the clinical, cytogenetic, and outcome features of childhood acute megakaryoblastic leukemia (AMKL), we reviewed 24 cases; 14 were identified among 150 consecutive newly diagnosed acute myelogenous leukemia (AML) patients at St. Jude Children's Research Hospital, and 10 were cases referred to the National Institute of Cancer in Rio de Janeiro, Brazil. There were 5 Down syndrome patients and one patient with chronic myeloid leukemia (Ph+) in blastic crisis. Twelve patients had significant hepatosplenomegaly. Leukemic cell morphology and cytochemistry were consistent with the M7 classification in 17 cases, and all cases tested expressed megakaryocytic surface antigens. AMKL patients were significantly younger than other AML patients (P = 0.0001) and had poorer responses to therapy (P = 0.03, univariate analysis only). Ten of 24 failed induction, and only 5 are disease-free at 6 months to 4.5+ years. We conclude that AMKL usually affects young children, frequently producing marked organomegaly. It comprises approximately 10% of pediatric AML cases, and responds poorly to intensive AML therapies.