RESUMO
We report a high incidence of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) in patients entered into the preceding Medical Research Council Chronic Lymphocytic Leukaemia Pilot study of autografting [corrected] Of 115 newly diagnosed patients treated with fludarabine, 65 patients proceeded to autologous transplant. Conditioning was cyclophosphamide and total body irradiation in 49 (75%) patients and chemotherapy in 12 (18%). Ten patients have developed MDS/AML; eight had undergone an autograft. Five-year actuarial risk of developing MDS/AML postautograft was 12.4% (95% confidence interval, 2.5-24%). No analysed potential risk factor was predictive for MDS/AML development. We hypothesise that potential causative factors are fludarabine, low cell dose and transplant conditioning.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Mieloide/terapia , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Doença Aguda , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Fosfato de Vidarabina/efeitos adversos , Fosfato de Vidarabina/análogos & derivados , Fosfato de Vidarabina/uso terapêuticoRESUMO
Chronic lymphocytic leukaemia (CLL) is characterised by the accumulation of mature B lymphocytes. Defects in the tumour suppressor gene p53 pathway are known to be important in CLL and p53 inactivation is associated with a particularly aggressive form of CLL. A single nucleotide polymorphism (SNP) in codon 72 of TP53 leads to a single amino acid change leading to a change in apoptotic potential and alters prognosis in squamous carcinomas. A polymorphism within intron 6 of TP53 has been postulated to alter the susceptibility to lung cancer. Our study looked at the influence of these two polymorphisms in a cohort of approximately 200 CLL patients. The codon 72 polymorphism A2/A2 genotype (homozygous arginine) was associated with an increased susceptibility to CLL and CD38 negativity but did not appear to influence other biological behaviour or clinical response. The intron 6 polymorphism A2/A2 genotype was strongly associated with early stage disease, CD38 negativity and a longer time to first treatment. The effect on time to treatment did not retain significance in multivariate analysis and the polymorphism did not predict for overall survival (OS). Detailed investigation of the complete TP53 genotype is warranted to further characterise the role of SNPs in p53 and their influence on CLL.
