RESUMO
Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m(2) daily on days 1-5, followed after 3 hr by cytarabine at 1 g/m(2) daily on days 1-5. Ten patients received a further consolidation cycle with clofarabine at 22.5 mg/m(2) and cytarabine at 1 g/m(2) day 1-4. Among the 47 patients, 24/47 (51%) achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a resistant disease, and 6/47 (13%) died of complications during the aplastic phase. The most frequent nonhematologic adverse events were vomiting, diarrhea, transient liver toxicity, febrile neutropenia, and infections microbiologically documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone marrow transplantation. In 14 patients, complete remission duration was shorter than 12 months, whereas 10 patients experienced longer complete remission duration. These very preliminary results suggest that clofarabine-cytarabine regimen is effective in this particularly poor prognosis category of patients, representing a potential "bridge" toward bone marrow transplant procedures. Safety data were consistent with previously reported salvage therapies. Further studies and a longer follow up are warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Nucleotídeos de Adenina/administração & dosagem , Nucleotídeos de Adenina/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arabinonucleosídeos/administração & dosagem , Arabinonucleosídeos/efeitos adversos , Clofarabina , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
Background. In acute myeloid leukemia (AML), CXCR4 expression has been correlated with leukocytosis and prognosis. Methods. We quantified CXCR4 expression by flow cytometry on leukemic cells in 142 AML patients. Results. We confirm a correlation between high CXCR4 expression and leukemic burden. Furthermore, we documented a correlation with platelet count, dysplastic megakaryopoiesis, hepato-splenomegaly and extra-hematological disease. NPM1-mutated AML displayed a significantly higher intensity of CXCR4 compared to NPM1-wt cases: it is conceivable its clinical phenotype to be driven by high CXCR4 expression. Conclusions. CXCR4 expression resulted an independent prognostic factor. Our data support CXCR4 targeting as a potential therapeutic strategy. © 2014 Clinical Cytometry Society.
RESUMO
BACKGROUND: In acute myeloid leukemia (AML), CXCR4 expression has been correlated with leukocytosis and prognosis. METHODS: We quantified CXCR4 expression by flow cytometry on leukemic cells in 142 AML patients. RESULTS: We confirm a correlation between high CXCR4 expression and leukemic burden. Furthermore, we documented a correlation with platelet count, dysplastic megakaryopoiesis, hepato-splenomegaly and extra-hematological disease. NPM1-mutated AML displayed a significantly higher intensity of CXCR4 compared to NPM1-wt cases: it is conceivable its clinical phenotype to be driven by high CXCR4 expression. CONCLUSIONS: CXCR4 expression resulted in an independent prognostic factor. Our data support CXCR4 targeting as a potential therapeutic strategy.