RESUMO
Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19-3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease.
Assuntos
Injúria Renal Aguda , Arsenicais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Leucemia Promielocítica Aguda , Humanos , Trióxido de Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Obesidade/complicações , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Arsenicais/efeitos adversos , Óxidos/efeitos adversosRESUMO
Patients with acute myeloid leukemia (AML) and internal tandem duplication of FMS-like tyrosine kinase receptor-3 gene (FLT3-ITD) mutation have poor prognoses and are often treated with allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. We treated 16 patients with FLT3-ITD-positive AML who relapsed after HSCT with sorafenib alone (n = 8) or in combination with cytotoxic chemotherapy (n = 8). The number of circulating blasts decreased in 80% of cases, but none of the patients achieved complete remission (CR); 3 achieved partial remission. Two patients were bridged to a second transplantation but both relapsed within 3 months of the transplantation. Median overall survival (OS) was 83 days, with none surviving more than a year. Sorafenib is not effective in the treatment of FLT3-ITD-positive AML relapsing after HSCT. Preventive strategies after HSCT may be more suitable for these high-risk patients.