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Eur J Haematol ; 100(5): 436-443, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29384595


OBJECTIVE: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML). METHODS: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed. RESULTS: MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT. CONCLUSION: We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.

Regiões 3' não Traduzidas , Biomarcadores Tumorais , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , RNA Mensageiro , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Hibridização in Situ Fluorescente , Lactente , Estimativa de Kaplan-Meier , Cariótipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Proteína do Locus do Complexo MDS1 e EVI1/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Prognóstico , Modelos de Riscos Proporcionais , Translocação Genética , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genética
Ann Hematol ; 97(3): 533-535, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29151134
Br J Haematol ; 172(3): 428-38, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26567765


The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing (NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P = 0·038), shorter progression-free survival (PFS; P = 0·007) and overall survival (OS; P = 0·009). The integrative analysis of array-CGH and NGS showed that 26·3% (5/19) and 36·8% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P = 0·011) while TCF3 alterations were associated with shorter OS (P = 0·032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/genética , Aberrações Cromossômicas , Adolescente , Adulto , Idoso , Hibridização Genômica Comparativa/métodos , Feminino , Genoma , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Rituximab/administração & dosagem , Resultado do Tratamento , Adulto Jovem
Transfusion ; 55(4): 875-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25354577


BACKGROUND: High-dose chemotherapy supported by autologous stem cell transplantation (ASCT) is an effective treatment for patients with lymphomas. However, failure to reach the minimum threshold of hematopoietic stem cells to proceed to ASCT may occur, even with the most effective strategies currently available. STUDY DESIGN AND METHODS: We report on 33 patients diagnosed with lymphoma who had at least one prior mobilization failure and received cytarabine at a dose of 400 mg/m(2) /day intravenously × 3 days plus granulocyte-colony-stimulating factor (G-CSF) 10 to 12 µg/kg/day as mobilization regimen. The median number of previous lines of chemotherapy was three. RESULTS: Thirty-two of 33 patients (96.8%) reached the target CD34+ cell dose (>2 × 10(6) /kg). The mean (range) number of apheresis procedures was 1.8 (1-3) with 4.69 × 10(6) (1.5 × 10(6) -6.8 × 10(6) )/kg CD34+ cells obtained. All but one patient received chemomobilization in the outpatient department. Severe infections or treatment-related mortality were not observed. All patients that received ASCT (31/33) engrafted without requiring G-CSF during the posttransplant period. CONCLUSION: This study shows that cytarabine at intermediate doses plus G-CSF in patients diagnosed with lymphoma who had a prior mobilization failure is a feasible and effective mobilization regimen.

Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Células , Terapia Combinada , Citarabina/farmacologia , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
Eur J Haematol ; 91(5): 448-55, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23710624


BACKGROUND: The standard practice in allogeneic stem cell transplant (alloSCT) is to infuse peripheral blood stem cells (PBSC) the same day or the day after collection once the patient has received conditioning regimen. To obtain and freeze PBSC prior to SCT would be desirable to get a better logistic and to confirm the quality of the product. Unfortunately, studies comparing both approaches are lacking. AIM: In this retrospective study, we analyze the impact of using fresh (N: 107) or previously frozen PBSC (N: 224) on overall outcomes among patients consecutively undergoing alloPBSCT from a matched related donor. RESULTS: Granulocyte engraftment (>500/mcl × 3 days) was faster in the frozen group (14 vs. 16 days, respectively; P = 0.001), while no significant differences on platelet recovery were observed. Patients receiving frozen PBSC had a higher incidence of global acute graft-versus-host disease (aGVHD) (63 vs. 44%, P < 0.001) mostly involving skin and had an earlier onset (13 vs. 30 days, P < 0.001). Response to first-line treatment with corticoids was similar in both groups. No statistically significant differences were found regarding overall chronic GVHD (58 vs. 66%) nor global survival (44 vs 48%), disease-free survival (39 vs. 33%), non-relapse mortality (24 vs. 16% at 1 year), and relapse rates in the frozen vs. fresh group, respectively. CONCLUSIONS: Infusion of previously frozen stem cells may achieve similar overall outcomes compared to fresh infusion, allowing to program donor apheresis and transplantation. However, cryopreservation might influence on the different pattern of aGVHD, issue that deserves further studies.

Criopreservação , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Antígenos HLA/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
Clin Lymphoma Myeloma Leuk ; 13(2): 144-52, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23137720


UNLABELLED: Prognosis of myelodysplastic syndromes (MDS) is an area of ongoing interest. Identification of patients with poor outcome in the categories of lower risk disease is critical. In this study, we classify a cohort of 332 lower risk MDS into 3 groups with differences in survival and risk for leukemic progression that could drive treatment approaches to improve prognosis in a fraction of these patients. BACKGROUND: Prognosis of MDS and particularly in patients categorized as lower risk (< 10% blasts or low and intermediate-1 International Prognostic Scoring System [IPSS]) is very heterogeneous and includes patients with very different outcomes with current scoring systems. Recently, a new cytogenetic classification has been proposed for the revised IPSS in predicting the outcome for MDS. PATIENTS AND METHODS: To evaluate the prognostic significance of multiple variables for survival and risk of progression to acute myeloid leukemia, we analyzed baseline characteristics of 332 lower risk MDS patients within the lower risk cytogenetic categories by IPSS and the recent proposal for the new cytogenetic classification. RESULTS: In multivariate analysis, severity of cytopenias, age > 60 years, bone marrow blasts (5%-9%) and transfusion dependency significantly influenced outcome. The combination of these variables allowed development of a model which categorizes patients in 3 different groups with median survival of 95, 44, and 13 months for groups 1, 2, and 3, respectively (P < .001). In addition, this score also stratified patients for their risk for leukemic progression, estimated at 2 years in 3.1%, 7.6%, and 21.3% for each group (P = .024). CONCLUSION: Although karyotype remains the main prognostic factor in MDS, the current study identifies clinical parameters predicting outcome among patients with the better cytogenetic profile. Degree of cytopenias, blasts 5%-9% and transfusion dependence might identify a subset of patients within the nonadverse karyotype, in which early or more aggressive approaches could possibly be required to improve survival or prevent disease progression.

Células da Medula Óssea/patologia , Aberrações Cromossômicas , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/mortalidade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem