RESUMO
Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.
Assuntos
Fatores de Ligação ao Core/genética , Fatores de Ligação ao Core/metabolismo , Proteínas de Ligação a DNA/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Metilação de DNA , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Transdução de Sinais , Análise de Sobrevida , Translocação Genética , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: To perform a multivariate analysis by Cox proportional hazard model of the impact of JAK2 V617F mutation on thrombosis and myeloid transformations in patients with essential thrombocythemia (ET). PATIENTS AND METHODS: The clinicopathologic features and outcome of a cohort of Chinese ET patients were retrospectively reviewed. JAK2 V617F mutation was detected by allele-specific polymerase chain reaction. Potential risk factors including JAK2 V617F that might impact on thrombosis and outcome were studied by multivariate analysis with Cox proportional hazard model. RESULTS: Of 141 patients studied, JAK2 V617F was found in 80 cases (57%). JAK2 V617F was positively correlated with hemoglobin and leukocyte count at diagnosis. Univariate analysis showed significant thrombotic risks to be JAK2 V617F (P=0.006), hemoglobin >13 g/dl (P=0.015), and age >55 years (P=0.011). However, in multivariate analysis, only age and hemoglobin were independent risk factors. JAK2 V617F was unrelated to survival or leukemic/myelofibrotic transformation. CONCLUSION: In Chinese patients with ET, JAK2 V617F was positively associated with age, hemoglobin, and leukocyte count, but was not an independent risk for thrombosis.
Assuntos
Janus Quinase 2/genética , Leucemia Mieloide/genética , Mutação Puntual , Trombocitemia Essencial/complicações , Trombocitemia Essencial/genética , Trombose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Estudos de Associação Genética , Hemoglobinas/análise , Humanos , Leucemia Mieloide/etiologia , Contagem de Leucócitos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Trombocitemia Essencial/mortalidade , Trombocitemia Essencial/fisiopatologia , Trombose/etiologia , Adulto JovemRESUMO
Candida arthritis in patients with a haematological malignancy is rare. We report a case of Candida tropicalis arthritis of the knee that occurred in a patient with acute lymphoblastic leukaemia during the recovery phase of post-chemotherapy neutropenia. Although the Candida tropicalis isolates from synovial fluid and synovial tissue were sensitive to fluconazole in vitro, a 6-week course of oral treatment failed to produce clinical improvement. The arthritis resolved after 7 weeks of combination therapy with caspofungin, a new echinocandin class of antifungal agent that acts primarily on the cell wall. Eleven other reports of Candida arthritis in patients with a haematological malignancy were reviewed.