RESUMO
The introduction of targeted therapies has revolutionized treatment and improved outcomes in patients with leukemias and lymphomas. However, many patients experience relapse caused by the persistence of residual malignant cells. Cytogenetic and molecular techniques are increasingly being used to assess and quantify minimal residual disease (MRD). The emergence of advanced technologies has led to the discovery of multiple novel molecular markers that can be used to detect MRD and predict outcome in patients with leukemias and lymphomas. Gene expression signatures that predict clinical outcomes in patients with non-Hodgkin's lymphoma have been identified. In chronic myelogenous leukemia, molecular monitoring has become more important in assessing response and detecting resistance to therapy. In acute leukemias, several new markers have shown potential in prognostication and monitoring treatment. In leukemias and lymphomas, microRNAs have been identified that may be useful in diagnostics and prognostication. To address these issues, the National Comprehensive Cancer Network (NCCN) organized a task force consisting of a panel of experts in leukemia and lymphoma to discuss recent advances in the field of molecular markers and monitoring MRD.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , Linfoma não Hodgkin/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Biomarcadores Tumorais , Perfilação da Expressão Gênica , Fusão Gênica , Humanos , Imunofenotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , MicroRNAs/análise , Mutação , Neoplasia Residual , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , PrognósticoRESUMO
This report describes our experience with reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using matched sibling and unrelated donors (MUDs) for treatment of myelofibrosis (MF). Nine patients with MF (median age, 54 years) were treated with RIC allogeneic HCT using MUDs for 7 of the 9 patients and sibling donors for 2 patients. By the Lille classification, 4 patients were characterized as having high risk, 4 as having intermediate risk, and 1 as having low risk. The RIC regimen consisted of fludarabine and a single dose of total body irradiation for the first patient and fludarabine/melphalan for the remaining 8 patients. Granulocyte colony-stimulating factor-primed peripheral blood stem cells (PBSCs) were used for all but 1 patient who received a total of 3 products because of graft failure, of which 2 were bone marrow cells and the third was PBSCs. Prophylaxis against graft-versus-host disease consisted of cyclosporin/mycophenolate with or without methotrexate. Seven patients were successfully engrafted with white blood cells, with an absolute neutrophil count > or =500 by a median of day +15 (range, 10-21 days). At the time of final fluorescence in situ hybridization and/or short tandem repeat analysis, 8 of 9 patients were chimeric, with 96%-100% donor cells and/or DNA. Five of the 9 patients were alive at the time of final contact, with a median follow-up of 32.2 months for the living patients. Overall survival probability at 1 year was 55.6% (95% confidence interval, 31.3%-77.4%). These results suggest that RIC MUD HCT using PBSCs can be an effective treatment for older patients with MF.