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1.
Biol Blood Marrow Transplant ; 25(5): 941-948, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30503388

RESUMO

Cytogenetic and genetic changes have prognostic significance in acute myelogenous leukemia (AML). In our study, we compared the cytogenetic changes and gene mutations (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) with clinical outcomes in 1132 patients with AML enrolled at our center over a 10-year period. A total of 977 patients provided gene mutation data. There were subsets of patients who exhibited mutations in NPM1 (17.9%), CEBPA (16.4%), FLT3-ITD (18.5%), FLT3-TKD (3.9%), DNMT3A (8.6%), and C-KIT (8.8%). A total of 557 patients (49.2%) underwent hematopoietic stem cell transplantation (HSCT) as consolidation therapy. Multivariate analysis identified an adverse karyotype (hazard ratio [HR], 1.48; P = .001), the presence of FLT3-ITD (HR, 1.90; P < .001), and receipt of nonstandard first-line induction chemotherapy (HR, 1.45; P = .003) as significant risk factors for poor overall survival (OS), and the presence of CEBPAmut (HR, .42; P < .001) and receipt of HSCT (HR, .35; P < .001) as prognostic factors for favorable OS. In addition, the presence of FLT3-ITDmut (HR, 2.11; P < .001) was identified as an independent risk factor for poor disease-free survival (DFS), and receipt of HSCT was correlated with improved DFS (HR, .74; P = .046). Compared with chemotherapy as consolidation therapy, HSCT improved the prognosis and overcame the prognostic effect of karyotype from the initial diagnosis; however, the presence of FLT3-ITD or CEBPA mutation can predict prognosis in AML irrespective of HSCT.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Indução de Remissão/métodos , Fatores de Risco , Adulto Jovem
2.
Ann Hematol ; 98(4): 987-996, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30715567

RESUMO

Epstein-Barr virus (EBV) reactivation is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). In this study, we investigated the characteristics of EBV reactivation in 186 consecutive myelodysplastic (MDS) patients who underwent allo-HSCT in our centre. In 35 patients (18.8%) who experienced EBV reactivation after allo-HSCT, the median onset was 53 days (range 4-381 days). The cumulative incidence of EBV reactivation at the first, sixth, and twelfth month after allo-HSCT was 10.7%, 15.1%, and 17.9%, respectively. Twenty-five patients (71.4%) received pre-emptive rituximab therapy, and no patients developed post-transplant lymphoproliferative disorders. Stem cell source was proven to be a risk factor correlated with EBV reactivation. The cumulative incidence of relapse in the EBV-positive group was 11.4%, 25.2%, and 31.0% at the first, second, and third year after transplantation, respectively, being significantly higher than the corresponding 6.8%, 10.2%, and 10.2%, in the EBV-negative group (P = 0.014). Prognostic analysis showed that EBV reactivation was an independent risk factor for relapse-free survival (RFS). Patients in the EBV-positive group showed obviously shorter RFS than those in the EBV-negative group, with 3-year RFS of 62% and 85%, respectively (P = 0.017).


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Síndromes Mielodisplásicas , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Fatores de Risco , Rituximab/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo
3.
J Cancer Res Clin Oncol ; 147(9): 2659-2670, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33550446

RESUMO

PURPOSE: Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. METHODS: We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years. RESULTS: A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPAwt were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPAmut/FLT3-ITDwt had the best prognosis, and patients with CEBPAwt/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. CONCLUSIONS: We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Mutação , Neoplasia Residual/mortalidade , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Citogenética , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Nucleofosmina , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 731-736, 2020 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32552928

RESUMO

OBJECTIVE: To compare the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and post-remission chemotherapy (PR-CT) in treatment of intermediate risk acute myeloid leukemia with negative for FLT3-ITD, NPM1 or biallelic CEBPA mutation. METHODS: The clinical data of patients with intermediate risk NPM1wt/non-CEBPAdm/FLT3-ITDneg AML from October 2009 to May 2016 were retrospectively analyzed. RESULTS: The overall survival rate of the patients treated with PR-CT, MSD-HSCT or hi-HSCT was 63.7%, 71.7%, 75.5%, respectively (P<0.05); the disease-free survival (DFS) rate was 52.8%, 67.1%, 71.3% respectively (P<0.001); the cumulative incidence of relapse was 24.7%, 16.9%, 14.4% respectively (P<0.05); the non-relapse mortality was 26.2%, 17.3%, 14.4% reapectively (P>0.05). The analysis of transplantation, related adverse events showed that II-IV grade of aGVHD in the MSD-HSCT group and hi-HSCT group was 48.9% and 45.6% respectively (P>0.05); the extensive cGVHD event was 21.6% and 8.8% (P<0.05) respectively. CONCLUSION: The efficiency of hi-HSCT and MSD-HSCT is superior to that of PR-CT for treatment of patients with intermediate risk NPM1wt/non-CEBPAdm/FLT3-ITDneg AML after CR1, there is no statistically significant difference in the efficiency of consolidatorg treatment and the transplantation-related mortality between hi-HSCT and MSD-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Proteínas Estimuladoras de Ligação a CCAAT , Humanos , Mutação , Proteínas Nucleares , Nucleofosmina , Prognóstico , Estudos Retrospectivos , Tirosina Quinase 3 Semelhante a fms
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